bluuebunny/crossref_metadata_2025 huggingface dataset:
Retention performances of green roofs worldwide at different time scales
Authors: Hellies Matteo , Deidda Roberto , Viola Francesco
Published: March 2018

Urbanization process is rapidly converting forested areas and grasslands to residential, commercial, or industrial spaces, triggering soil degradation and significantly increasing impervious surfaces. Consequently, man‐made environments experience significant decrease of infiltration and groundwater recharge, enhancing the problems related to the management and protection from increased stormwater runoff. Green roofs are structural measures able to mitigate these negative drawbacks due to anthropic transformation, retaining and detaining stormwater runoff, with the main advantage of reducing hydraulic loads on combined storm sewer systems. Hydrological performance of green roofs have been studied in different parts of the world under different climatic conditions, but a comprehensive study that provides global responses, even in an approximate way, is still missing. The aim of this work is to assess the convenience and the feasibility of installing green roofs in any target area of the world, providing a rough indication of geographic regions where green roof installation is possible with good hydrological performance, and feasible in rainfed conditions with low vegetation water stress. To do that, we explored in silico green roofs' hydrological performance worldwide, using climatological forcings from ERA‐Interim database as input for a simple conceptual hydrological model to estimate green roof outputs, in terms of evapotranspiration and runoff.
Soil organic carbon recovery and coffee bean yield following bauxite mining
Authors: Vilas Boas Hiran F. , Almeida Luis F. J. , Teixeira Rafael S. , Souza Ivan F. , Silva Ivo R.
Published: March 2018

Bauxite mining requires the removal of the vegetation and topsoil, thus causing considerable impacts on both natural and managed ecosystems. This is typically the case of agricultural activities across Minas Gerais, South‐eastern Brazil, where bauxite mining often displaces pastures and coffee plantations. In this study, our objective was to assess the effects of chemical and organic fertilizations combined with cover crops on the re‐establishment of coffee plantations following bauxite mining. The experiment consisted of a split‐plot design which main plot received 4 types of fertilization: no fertilization, chemical fertilization (CF), poultry litter (PL), and CF + PL. In subplots, 4 cover crops were cultivated in between the rows of the coffee plantation, including: no cover crops, grass (Brachiaria brizantha [B]), legume (Stylosanthes spp. [S]), and B + S. We had 4 blocks as replicates. Organic and chemical fertilization (PL + CF) combined with cover crops (B + S) led to significant recovery of soil organic carbon (SOC), soil organic nitrogen (SON), and KMnO4‐oxidizable SOC. PL + CF and B + S also led to SOC increments of 14.5 g kg−1 soil (0–10‐cm depth). Based on isotopic data (13C), both cover crops, isolated or combined, contributed to the recovery of SOC. Over 3 consecutive harvests, coffee bean yield was consistently above 1,800 kg ha−1 under PL or PL + CF, except when B was the only cover crop. Managing fertilization and cover crops can determine the recovery of SOC, SON and the capacity of soil to sustain the re‐establishment of coffee plantations following bauxite mining.
Changes in soil organic carbon fractions in response to different tillage practices under a wheat‐maize double cropping system
Authors: Xue Jian‐Fu , Pu Chao , Zhao Xin , Wei Yan‐Hua , Zhai Yun‐Long , Zhang Xiang‐Qian , Lal Rattan , Zhang Hai‐Lin
Published: March 2018

To understand the turnover of soil organic carbon (SOC) and the improvement of soil quality in response to tillage practices, it is important to identify changes in labile SOC fractions, for example, permanganate oxidizable organic carbon (POxC) and particulate organic carbon (POC). Five tillage treatments were initially undertaken in a winter wheat (Triticum aestivum L., mid‐October to early‐June)–summer maize (Zea mays L., mid‐June to early‐October) system in the North China Plain in 2008 with changes being examined in 2012–2013. These treatments included plough tillage with residue removed, plough tillage with residue incorporation, no tillage with residue mulching, subsoiling with residue incorporation, and rotary tillage (tillage with a rotary tiller) with residue incorporation for the winter wheat season; summer maize was only managed with the NTM treatment. The greatest POxC and POC concentrations at the 0–5‐cm depth were observed under RTR and NTM treatments (p < .05), respectively. Both STR and RTR recorded larger POxC and POC concentrations at the 5–10‐cm depth (p < .05). Both POxC and POC concentrations for STR treatment were significantly higher than those under RTR, NTM, and PT0 treatments in the 20–50‐cm soil profile. The POC concentrations in each soil layer of 0–30‐cm showed a significant response to residue amount, temperature, and precipitation; and POxC concentrations did not record similar responses. Therefore, subsoiling with residue incorporation could be a potential tillage practice to manage labile SOC pool in top soil (0–50‐cm) in the North China Plain region.
Tree species and recovery time drives soil restoration after mining: A chronosequence study
Authors: Kim Songho , Zang Huadong , Mortimer Peter , Shi Lingling , Li Yunju , Xu Jianchu , Ostermann Anne
Published: March 2018

Open‐pit mining activities for metals and minerals have impacted vast areas of the Earth's surface and left behind highly disturbed and degraded landscapes. However, our understanding of tree species and recovery time on the restoration of biotic and abiotic soil properties remains incomplete. Topsoil (0–15 cm) was collected from plantations of 4 tree species: alder, acacia, pine, and cypress. A chronosequence of restoration was selected to assess the effect of recovery time: vegetation‐free postmining land (unrestored control), 5–10 years (young plantation), and 20–25 years (old plantation). The soil physicochemical characteristics and phospholipid fatty acids were analysed. After 20 years of restoration, the soil organic carbon (SOC) concentration increased, on average, from 1.4% to 4.7% for alder, cypress, and acacia. However, SOC was similar under pine plantations in unrestored control and at the late stage of restoration. The restoration of soil total nitrogen was faster than the SOC pools for all tree species investigated. Compared with that in the unrestored control, the total microbial biomass increased by 74% after 20–25 years of restoration. A similar increase was observed for bacterial biomass. The studied sites partly exhibited residues of trace elements that exceeded Chinese environmental quality standards (Cd, As, Cu, and Cr). However, only Cu affected the soil community; arbuscular mycorrhizal biomass decreased with an increase in Cu concentration. In conclusion, the recovery time, rather than the tree species, was the main determinant in the alteration of key soil physicochemical parameters in the restoration of phosphate‐mining‐degraded landscapes, at least during the first 20–25 years.
Effects of rotational prescribed burning and sheep grazing on moorland plant communities: Results from a 60‐year intervention experiment
Authors: Milligan Gregg , Rose Rob J. , O'Reilly John , Marrs Rob H.
Published: March 2018

The effect of prescribed burning for conservation management of plant communities is controversial for moorlands growing on peat. These ecosystems provide many services that may be damaged by fire, hence it is important to fully assess its impact on all aspects of ecosystem structure and function experimentally over relatively long time‐scales. This paper describes change in community composition, major plant species, and plant functional types on moorland on peat in upland Britain over 60 years subject to 3 burning treatments after an initial burn in 1954/1955: no further burn and burning at 10‐ and 20‐year intervals (all ± sheep grazing). Data were analysed using multivariate and univariate methods. Vegetation composition and individual species abundance reflected the degree of disturbance. The least disturbed was dominated by Calluna vulgaris and pleurocarpous mosses, whereas the most disturbed treatment (burned every 10 years) had greater Eriophorum vaginatum, Sphagnum spp., acrocarpous mosses, liverworts, and lichens. The 20‐year treatment was intermediate in response disturbance. Repeated burning increased species abundance‐weighted Ellenberg values for moisture, reaction, light through time, and fertility; the exception was the 10‐year rotation for fertility. These confirm that prescribed burning is not deleterious to peat‐forming species (Eriophorum spp. and Sphagnum spp.), indeed these species were found in greater abundance in frequently burned treatments. It also confirms that a no‐burn policy will lead to increasing dominance of C. vulgaris, a flammable, fire‐adapted shrub, which increases summer wildfire risk. These results inform conservation management policy for moorland vegetation growing on peat; for this site, a 20‐year prescribed burning rotation is recommended.
An experimental investigation of a novel iron chelating protoporphyrin IX prodrug for the enhancement of photodynamic therapy
Authors: Anayo Lizette , Magnussen Anette , Perry Alexis , Wood Mark , Curnow Alison
Published: March 2018

Objectives

Non‐melanoma skin cancers are the most frequently occurring type of cancer worldwide. They can be effectively treated using topical dermatological photodynamic therapy (PDT) employing protoporphyrin IX (PpIX) as the active photosensitising agent as long as the disease remains superficial. Novel iron chelating agents are being investigated to enhance the effectiveness and extend the applications of this treatment modality, as limiting free iron increases the accumulation of PpIX available for light activation and thus cell kill.

Methods

Human lung fibroblasts (MRC‐5) and epithelial squamous carcinoma (A431) cells were treated with PpIX precursors (aminolaevulinic acid [ALA] or methyl‐aminolevulinate [MAL]) with or without the separate hydroxypyridinone iron chelating agent (CP94) or alternatively, the new combined iron chelator and PpIX producing agent, AP2‐18. PpIX fluorescence was monitored hourly for 6 hours prior to irradiation. PDT effectiveness was then assessed the following day using the lactate dehydrogenase and neutral red assays.

Results

Generally, iron chelation achieved via CP94 or AP2‐18 administration significantly increased PpIX fluorescence. ALA was more effective as a PpIX‐prodrug than MAL in A431 cells, corresponding with the lower PpIX accumulation observed with the latter congener in this cell type. Addition of either iron chelating agent consistently increased PpIX accumulation but did not always convey an extra beneficial effect on PpIX‐PDT cell kill when using the already highly effective higher dose of ALA. However, these adjuvants were highly beneficial in the skin cancer cells when compared with MAL administration alone. AP2‐18 was also at least as effective as CP94 + ALA/MAL co‐administration throughout and significantly better than CP94 supplementation at increasing PpIX fluorescence in MRC5 cells as well as at lower doses where PpIX accumulation was observed to be more limited.

Conclusions

PpIX fluorescence levels, as well as PDT cell kill effects on irradiation can be significantly increased by pyridinone iron chelation, either via the addition of CP94 to the administration of a PpIX precursor or alternatively via the newly synthesized combined PpIX prodrug and siderophore, AP2‐18. The effect of the latter compound appears to be at least equivalent to, if not better than, the separate administration of its constituent parts, particularly when employing MAL to destroy skin cancer cells. AP2‐18 therefore warrants further detailed analysis, as it may have the potential to improve dermatological PDT outcomes in applications currently requiring enhancement. Lasers Surg. Med. 50:552–565, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.
Clinical Course of Hepatic Artery Thrombosis After Living Donor Liver Transplantation Using the Right Lobe
Authors: Choi Ho Joong , Kim Dong Goo , Kim Yumi , Kwak Bong Jun , Han Jae Hyun , Hong Tae Ho , You Young Kyoung
Published: March 2018

Hepatic artery thrombosis (HAT) can result in biliary tree necrosis and graft loss, necessitating retransplantation. The most effective treatment approach is still controversial. This study was performed to review the outcomes of HAT after living donor liver transplantation (LDLT) and to clarify the feasibility of different strategies. From May 1996 to August 2017, LDLT using the right lobe was performed in 827 adult patients in our center. Our technique of hepatic artery (HA) reconstruction is end‐to‐end anastomosis under a microscope (10×). Diagnosis of HAT was performed using Doppler sonography and computed tomography (CT) angiography. HAT was initially treated with surgical or endovascular procedure, and retransplantation was considered according to the graft condition. Among the 827 cases of LDLT using the right lobe, HAT occurred in 16 (1.9%) cases within 1 month after transplantation. Within the first week, 7 of these HAT cases (43.8%) occurred (early HAT), while the remaining 9 cases (56.2%) occurred between the first week and 1 month (late HAT). The incidence of graft failure was high in early HAT (42.9%), and the frequency of biliary complications was high in late HAT (77.8%). The success rate of HA recanalization was 62.5% (10/16): 100% (5/5) after reoperation and 45.5% (5/11) after the endovascular procedure. Of the patients in whom treatment failed in late HAT (n = 5), 4 underwent neovascularization during observation. A total of 5 patients underwent graft failure, and 3 of these patients underwent repeat liver transplantation (LT). Mortality occurred in 3 patients, including 1 in the surgical group and 2 in the endovascular group. In conclusion, early diagnosis and aggressive treatment of HAT are necessary to avoid graft failure, and the choice of treatment depends on various factors. Although further studies are required, early HAT requires preparation for graft failure, while late HAT requires treatment for biliary complications.
Unilateral problems for the wave equation with degenerate and localized nonlinear damping: well‐posedness and non‐stability results
Authors: Cavalcanti A. D. D. , Cavalcanti M. M. , Fatori L. H. , Silva M. A. Jorge
Published: March 2018

Unilateral problems related to the wave model subject to degenerate and localized nonlinear damping on a compact Riemannian manifold are considered. Our results are new and concern two main issues: (a) to prove the global well‐posedness of the variational problem; (b) to establish that the corresponding energy functional is not (uniformly) stable to equilibrium in general, namely, the energy does not converge to zero on the trajectory of every solution, even if a full linear damping is taken in place.
Navier–Stokes equations with external forces in time‐weighted Besov spaces
Authors: Kozono Hideo , Shimizu Senjo
Published: March 2018

We show existence theorem of global mild solutions with small initial data and external forces in the time‐weighted Besov space which is an invariant space under the change of scaling. The result on local existence of solutions for large data is also discussed. Our method is based on the ‐ estimate of the Stokes equations in Besov spaces. Since we construct the global solution by means of the implicit function theorem, as a byproduct, its stability with respect to the given data is necessarily obtained.
A note on lattice ordered ‐algebras and Perron–Frobenius theory
Authors: Glück Jochen
Published: March 2018

A classical result of Sherman says that if the space of self‐adjoint elements in a ‐algebra is a lattice with respect to its canonical order, then is commutative. We give a new proof of this theorem which shows that it is intrinsically connected with the spectral theory of positive operator semigroups. Our methods also show that some important Perron–Frobenius like spectral results fail to hold in any non‐commutative ‐algebra.
Electron‐ion reaction‐based dissociation: A powerful ion activation method for the elucidation of natural product structures
Authors: Chen Xiangfeng , Wang Ze , Wong Y.‐L. Elaine , Wu Ri , Zhang Feng , Chan T.‐W. Dominic
Published: March 2018

The structural elucidation of natural products (NPs) remains a challenge due to their structurally diversities and unpredictable functionalities, motifs, and scaffolds. Tandem mass spectrometry (MS/MS) is an effective method that assists the full elucidation of complicated NP structures. Ion activation methods play a key role in determining the fragmentation pathways and the structural information obtained from MS/MS. Electron‐ion reaction‐based dissociation (ExD) methods, including electron capture dissociation (ECD), electron transfer dissociation (ETD), electron‐induced dissociation (EID), and electron detachment dissociation (EDD), can induce the breakage of specific chemical bonds and the generation of distinct fragment ions. This review article provides an overview of the mechanisms, instrumentation, and typical applications related to ExD MS/MS in the structural elucidation of NPs, primarly including lipids, oligosaccharides, glycoconjugates, metabolites, and pharmaceutical drugs. This work aims to reveal the capacity and potential of ExD mass spectrometry in analyzing NPs and consequently helping the NP communities to utilize the modern capabilities of MS/MS in the discovery and evaluation of novel NPs.
Hydrogen/deuterium exchange in mass spectrometry
Authors: Kostyukevich Yury , Acter Thamina , Zherebker Alexander , Ahmed Arif , Kim Sunghwan , Nikolaev Eugene
Published: March 2018

The isotopic exchange approach is in use since the first observation of such reactions in 1933 by Lewis. This approach allows the investigation of the pathways of chemical and biochemical reactions, determination of structure, composition, and conformation of molecules. Mass spectrometry has now become one of the most important analytical tools for the monitoring of the isotopic exchange reactions. Investigation of conformational dynamics of proteins, quantitative measurements, obtaining chemical, and structural information about individual compounds of the complex natural mixtures are mainly based on the use of isotope exchange in combination with high resolution mass spectrometry. The most important reaction is the Hydrogen/Deuterium exchange, which is mainly performed in the solution. Recently we have developed the approach allowing performing of the Hydrogen/Deuterium reaction on‐line directly in the ionization source under atmospheric pressure. Such approach simplifies the sample preparation and can accelerate the exchange reaction so that certain hydrogens that are considered as non‐labile will also participate in the exchange. The use of in‐ionization source H/D exchange in modern mass spectrometry for structural elucidation of molecules serves as the basic theme in this review. We will focus on the mechanisms of the isotopic exchange reactions and on the application of in‐ESI, in‐APCI, and in‐APPI source Hydrogen/Deuterium exchange for the investigation of petroleum, natural organic matter, oligosaccharides, and proteins including protein‐protein complexes. The simple scenario for adaptation of H/D exchange reactions into mass spectrometric method is also highlighted along with a couple of examples collected from previous studies.
Molecules and elements for quantitative bioanalysis: The allure of using electrospray, MALDI, and ICP mass spectrometry side‐by‐side
Authors: Linscheid Michael W.
Published: March 2018

To understand biological processes, not only reliable identification, but quantification of constituents in biological processes play a pivotal role. This is especially true for the proteome: protein quantification must follow protein identification, since sometimes minute changes in abundance tell the real tale. To obtain quantitative data, many sophisticated strategies using electrospray and MALDI mass spectrometry (MS) have been developed in recent years. All of them have advantages and limitations. Several years ago, we started to work on strategies, which are principally capable to overcome some of these limits. The fundamental idea is to use elemental signals as a measure for quantities. We began by replacing the radioactive 32P with the “cold” natural 31P to quantify modified nucleotides and phosphorylated peptides and proteins and later used tagging strategies for quantification of proteins more generally. To do this, we introduced Inductively Coupled Plasma Mass Spectrometry (ICP‐MS) into the bioanalytical workflows, allowing not only reliable and sensitive detection but also quantification based on isotope dilution absolute measurements using poly‐isotopic elements. The detection capability of ICP‐MS becomes particularly attractive with heavy metals. The covalently bound proteins tags developed in our group are based on the well‐known DOTA chelate complex (1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N‴‐tetraacetic acid) carrying ions of lanthanoides as metal core. In this review, I will outline the development of this mutual assistance between molecular and elemental mass spectrometry and discuss the scope and limitations particularly of peptide and protein quantification. The lanthanoide tags provide low detection limits, but offer multiplexing capabilities due to the number of very similar lanthanoides and their isotopes. With isotope dilution comes previously unknown accuracy. Separation techniques such as electrophoresis and HPLC were used and just slightly adapted workflows, already in use for quantification in bioanalysis. Imaging mass spectrometry (MSI) with MALDI and laser ablation ICP‐MS complemented the range of application in recent years.
Peptidyl‐prolyl cis/trans isomerase Pin1 regulates withaferin A‐mediated cell cycle arrest in human breast cancer cells
Authors: Samanta Suman K. , Lee Joomin , Hahm Eun‐Ryeong , Singh Shivendra V.
Published: March 2018

We have reported previously that withaferin A (WA) prevents breast cancer development in mouse mammary tumor virus‐neu (MMTV‐neu) transgenic mice, but the mechanism is not fully understood. Unbiased proteomics of the mammary tumors from control‐ and WA‐treated MMTV‐neu mice revealed downregulation of peptidyl‐prolyl cis/trans isomerase (Pin1) protein by WA administration. The present study extends these findings to elucidate the role of Pin1 in cancer chemopreventive mechanisms of WA. The mammary tumor level of Pin1 protein was lower by about 55% in WA‐treated rats exposed to N‐methyl‐N‐nitrosourea, compared to control. Exposure of MCF‐7 and SK‐BR‐3 human breast cancer cells to WA resulted in downregulation of Pin1 protein. Ectopic expression of Pin1 attenuated G2 and/or mitotic arrest resulting from WA treatment in both MCF‐7 and SK‐BR‐3 cells. WA‐induced apoptosis was increased by Pin1 overexpression in MCF‐7 cells but not in the SK‐BR‐3 cell line. In addition, molecular docking followed by mass spectrometry indicated covalent interaction of WA with cysteine 113 of Pin1. Overexpression of Pin1C113A mutant failed to attenuate WA‐induced mitotic arrest or apoptosis in the MCF‐7 cells. Furthermore, antibody array revealed upregulation of proapoptotic insulin‐like growth factor binding proteins (IGFBPs), including IGFBP‐3, IGFBP‐4, IGFBP‐5, and IGFBP‐6, in Pin1 overexpressing MCF‐7 cells following WA treatment when compared to empty vector transfected control cells. These data support a crucial role of the Pin1 for mitotic arrest and apoptosis signaling by WA at least in the MCF‐7 cells.
TGF‐β‐mediated LEFTY/Akt/GSK‐3β/Snail axis modulates epithelial‐mesenchymal transition and cancer stem cell properties in ovarian clear cell carcinomas
Authors: Matsumoto Toshihide , Yokoi Ako , Hashimura Miki , Oguri Yasuko , Akiya Masashi , Saegusa Makoto
Published: March 2018

Advanced ovarian clear cell carcinoma (OCCCa) shows poor prognosis with chemoresistance, which is associated with epithelial‐mesenchymal transition (EMT)/cancer stem cell (CSC) features. The left‐right determination factor (LEFTY), a novel member of the TGF‐β superfamily, is a marker of stemness. Here we focused on the functional roles of LEFTY in OCCCas. OCCCa cell lines that were cultured in STK2, a serum‐free medium for mesenchymal stem cells, or treated with TGF‐β1 underwent morphological changes toward an EMT appearance, along with increased expression of LEFTY and Snail. The cells also showed CSC properties, as demonstrated by increases in the aldehyde dehydrogenase (ALDH)1high activity population, number of spheroid formation, and expression of several CSC markers. Inhibition of LEFTY expression induced decreases in the number of spindle‐shaped cells and CSC features, while cells stably overexpressing LEFTY exhibited enhancement of such EMT/CSC properties. Finally, treatment of cells with TGF‐β1 led to increased LEFTY expression and activation of Akt, which subsequently induced inactivation of GSK‐3β, while inhibition of GSK‐3β resulted in increased expression of both LEFTY and Snail. In clinical samples, LEFTY expression showed a tendency for positive associations with expression of vimentin, as well as Sox2 and ALDH1, in OCCCas with epithelial‐like morphology, indicating a possible relationship between LEFTY and the epithelial‐mesenchymal hybrid stage of the tumors. In conclusion, TGF‐β‐mediated LEFTY/Akt/GSK‐3β/Snail axis may contribute to the establishment and maintenance of phenotypic characteristics of OCCCas through modulation of EMT/CSC properties.
Role of miR‐31 and SATB2 in arsenic‐induced malignant BEAS‐2B cell transformation
Authors: Chen Qiao Yi , Li Jinquan , Sun Hong , Wu Feng , Zhu Yusha , Kluz Thomas , Jordan Ashley , DesMarais Thomas , Zhang Xiaoru , Murphy Anthony , Costa Max
Published: March 2018

Arsenic is a naturally occurring and highly potent metalloid known to elicit serious public health concerns. Today, approximately 200 million people around the globe are exposed to arsenic‐contaminated drinking water at levels greater than the World Health Organization's recommended limit of 10 parts per billion. As a class I human carcinogen, arsenic exposure is known to elicit various cancers, including lung, skin, liver, and kidney. Current evidence suggests that arsenic is capable of inducing both genotoxic and cytotoxic injury, as well as activating epigenetic pathways to induce carcinogenesis. Our study identifies a novel pathway that is implicated in arsenic‐induced carcinogenesis. Arsenic down‐regulated miRNA‐31 and the release of this inhibition caused overexpression of special AT‐rich sequence‐binding protein 2 (SATB2). Arsenic is known to disrupt miRNA expression, and here we report for the first time that arsenic is capable of inhibiting miR‐31 expression. As a direct downstream target of miR‐31, SATB2 is a prominent transcription factor, and nuclear matrix binding protein implicated in many types of human diseases including lung cancer. Results from this study show that arsenic induces the overexpressing SATB2 by inhibiting miR‐31 expression, which blocks the translation of SATB2 mRNA, since levels of SATB2 mRNA remain the same but protein levels decrease. Overexpression of SATB2 induces malignant transformation of human bronchial epithelial (BEAS‐2B) cells indicating the importance of the expression of miR‐31 in preventing carcinogenesis by suppressing SATB2 protein levels.
Identification of chromatin‐accessible domains in non‐alcoholic steatohepatitis‐derived hepatocellular carcinoma
Authors: Dechassa Mekonnen L. , Tryndyak Volodymyr , de Conti Aline , Xiao Wenming , Beland Frederick A. , Pogribny Igor P.
Published: March 2018

Non‐alcoholic steatohepatitis (NASH) is becoming one of the major causes of hepatocellular carcinoma (HCC) in the United States and Western countries; however, the molecular mechanisms associated with NASH‐related liver carcinogenesis are not well understood. In the present study, we investigated cancer‐associated chromatin alterations using a model that resembles the development of NASH‐related HCC in humans. An assay for transposase‐accessible chromatin with high throughput sequencing (ATAC‐seq) identified 1677 tumor‐specific chromatin‐accessible regions in NASH‐derived HCC tissue samples. Using a combined analysis of ATAC‐seq and global gene expression data, we identified 199 differentially expressed genes, 139 up‐regulated and 60 down‐regulated. Interestingly, 15 of the 139 up‐regulated genes had accessible chromatin sites within 5 Kb of the transcription start site (TSS), including Apoa4, Anxa2, Serpine1, Igfbp1, and Tubb2a, genes critically involved in the development of NASH and HCC. We demonstrate that the mechanism for the up‐regulation of these genes is associated with the enrichment of chromatin‐accessible regions by transcription factors, especially NFATC2, and histone H3K4me1 and H3K27ac gene transcription‐activating marks. These data underline the important role of chromatin accessibility perturbations in reshaping of the chromatin landscape in NASH‐related HCC.
Short‐ and long‐term cost and utilization of health care resources in Parkinson's disease in the UK
Authors: Weir Sharada , Samnaliev Mihail , Kuo Tzu‐Chun , Tierney Travis S. , Walleser Autiero Silke , Taylor Rod S. , Schrag Anette
Published: March 2018

Background: There is currently no robust long‐term data on costs of treating patients with Parkinson's disease. The objective of this study was to report levels of health care utilization and associated costs in the 10 years after diagnosis among PD patients in the United Kingdom.

Methods: We undertook a retrospective population‐based cohort study using linked data from the UK Clinical Practice Research Datalink and Hospital Episode Statistics databases. Total health care costs of PD patients were compared with those of a control group of patients without PD selected using 1:1 propensity score matching based on age, sex, and comorbidity.

Results: Between 1994 and 2013, 7271 PD patients who met study inclusion criteria were identified in linked Clinical Practice Research Datalink‐Hospital Episode Statistics; 7060 were matched with controls. The mean annual health care cost difference (at 2013 costs) between PD patients and controls was £2471 (US$3716) per patient in the first year postdiagnosis (P < 0.001), increasing to £4004 (US$6021) per patient (P < 0.001) 10 years following diagnosis because of higher levels of use across all categories of health care utilization. Costs in patients with markers of advanced PD (ie, presence of levodopa‐equivalent daily dose > 1100 mg, dyskinesias, falls, dementia, psychosis, hospital admission primarily due to PD, or nursing home placement) were on average higher by £1069 (US$1608) per patient than those with PD without these markers.

Conclusions: This study provides comprehensive estimates of health care costs in PD patients based on routinely collected data. Health care costs attributable to PD increase in the year following diagnosis and are higher for patients with indicators of advanced disease. © 2018 International Parkinson and Movement Disorder Society
Genotype‐phenotype correlations, dystonia and disease progression in spinocerebellar ataxia type 14
Authors: Chelban Viorica , Wiethoff Sarah , Fabian‐Jessing Bjørn K. , Haridy Nourelhoda A. , Khan Alaa , Efthymiou Stephanie , Becker Esther B. E. , O'Connor Emer , Hersheson Joshua , Newland Katrina , Hojland Allan Thomas , Gregersen Pernille A. , Lindquist Suzanne G. , Petersen Michael B. , Nielsen Jørgen E. , Nielsen Michael , Wood Nicholas W. , Giunti Paola , Houlden Henry
Published: March 2018

Background: Spinocerebellar ataxia type 14 is a rare form of autosomal dominant cerebellar ataxia caused by mutations in protein kinase Cγ gene. Clinically, it presents with a slowly progressive, mainly pure cerebellar ataxia.

Methods: Using next generation sequencing, we screened 194 families with autosomal dominant cerebellar ataxia and normal polyglutamine repeats. In‐depth phenotyping was performed using validated clinical rating scales neuroimaging and electrophysiological investigations.

Results: We identified 25 individuals from 13 families carrying pathogenic mutations in protein kinase Cγ gene. A total of 10 unique protein kinase Cγ gene mutations have been confirmed of which 5 are novel and 5 were previously described. Our data suggest that the age at onset is highly variable; disease course is slowly progressive and rarely associated with severe disability. However, one third of patients presented with a complex ataxia comprising severe focal and/or task‐induced dystonia, peripheral neuropathy, parkinsonism, myoclonus, and pyramidal syndrome. The most complex phenotype is related to a missense mutation in the catalytic domain in exon 11.

Conclusion: We present one of the largest genetically confirmed spinocerebellar ataxia type 14 cohorts contributing novel variants and clinical characterisation. We show that although protein kinase Cγ gene mutations present mainly as slowly progressive pure ataxia, more than a third of cases had a complex phenotype. Overall, our case series extends the phenotype and suggests that protein kinase Cγ gene mutations should be considered in patients with slowly progressive autosomal dominant cerebellar ataxia, particularly when myoclonus, dystonia, or mild cognitive impairment are present in the absence of polyglutamine expansion. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Application of the Movement Disorder Society prodromal criteria in healthy G2019S‐LRRK2 carriers
Authors: Mirelman Anat , Saunders‐Pullman Rachel , Alcalay Roy N. , Shustak Shiran , Thaler Avner , Gurevich Tanya , Raymond Deborah , Mejia‐Santana Helen , Orbe Reilly Martha , Ozelius Laurie , Clark Lorraine , Gana‐Weisz Mali , Bar‐Shira Anat , Orr‐Utreger Avi , Bressman Susan B. , Marder Karen , Giladi Nir ,   the AJ LRRK2 Consortium
Published: March 2018

Background

In 2015, the International Parkinson and Movement Disorder Society Task Force recommended research criteria for the estimation of prodromal PD.

Objectives

We aimed to evaluate, for the first time, the criteria in first‐degree relatives of Ashkenazi Jewish G2019S‐LRRK2 PD patients, who are considered a population at risk for developing PD, and assess the sensitivity and specificity of the criteria in identifying phenoconverters.

Methods

Participants were evaluated longitudinally over a period of 5 years (average follow‐up: 49.2 ± 12.3 months). Likelihood ratios and probability estimations were calculated based on the International Parkinson and Movement Disorder Society Research Criteria for Prodromal Parkinson's Disease markers and examined for each assessment point.

Results

One hundred twenty healthy carriers (49.53 ± 13.4 years; 54% female) and 111 healthy noncarriers (48.43 ± 15.79 years; 49% female) participated in this study. Probability scores were significantly higher in healthy carriers than healthy noncarriers (P < 0.0001). Of the 20 participants (8.6%) who met criteria for probable prodromal PD at baseline, 17 were healthy carriers. Participants who reached the threshold were older (P < 0.0001), had higher UPDRS‐III (P < 0.001), lower cognitive function (P = 0.001), and more nonmotor symptoms (P < 0.0001), compared to those who did not. Ten participants were diagnosed with incident PD within 5 years from baseline resulting in a specificity of 91.82% (95% confidence interval: 86.69‐96.94), sensitivity of 80% (95% confidence interval: 55.21‐100), positive predictive value of 47.06% (95% confidence interval: 23.33‐70.79), and negative predictive value of 98.06% (95% confidence interval: 95.39‐100). All 10 phenoconvertors were G2019S‐LRRK2 carriers.

Conclusions

The results showed the utility of using the criteria and high sensitivity and specificity in identifying prodromal PD in this high‐risk unique cohort. These results may be valuable for future disease modification clinical trials. © 2018 International Parkinson and Movement Disorder Society
Intraoperative use of indocyanine green angiography for selecting the more reliable perforator of the anterolateral thigh flap: A comparison study
Authors: La Padula Simone , Hersant Barbara , Meningaud Jean Paul
Published: March 2018

Introduction

Anatomical variability of anterolateral thigh flap (ALT) perforators has been reported. The aim of this study is to assess if the use of intraoperative indocyanine green angiography (iICGA) can help surgeons to choose the ALT flap best perforator to be preserved.

Patients and methods

A retrospective study was conducted in 28 patients with open tibial fracture, following a road traffic crash, who had undergone ALT flap. Patients were classified into two groups: ICGA group (iICGA was used to select the more reliable perforator) and control group. The mean tissue loss size of the ICGA group (n = 13, 11 men and 2 women, mean age: 52 ± 6 years) was of 16.6 cm × 12.2 cm. The mean defect size of the control group (n = 15, 14 men and 1 women, mean age: 50 ± 5.52 years) was of 15.3 cm × 11.1 cm. Statistical analysis was performed to analyze and compare the results.

Results

ICGA allowed preserving only the most functional perforator, that provided the best ALT flap perfusion in 10 out of the 13 cases (77%). ICGA allowed a significant operative time reduction (160 ± 23 vs. 202 ± 48 minutes; P < .001). One case of distal necrosis was observed in the ICGA group (mean follow‐up 12.3 months), while partial skin necrosis occurred in three cases of the control group (mean follow‐up 13.1 months); P = .35. No additional coverage was required and a successful bone healing was observed in both groups.

Conclusions

These findings suggest that iICGA is an effective method that allows to select the most reliable ALT flap perforators and to reduce operative time.
Exact solution of a class of fractional integro‐differential equations with the weakly singular kernel based on a new fractional reproducing kernel space
Authors: Chen Zhong , Wu Longbin , Lin Yingzhen
Published: March 2018

In this paper, we construct a new fractional weighted reproducing kernel space, which is the minimum space containing the exact solution. The closed form of the reproducing kernel is obtained. Using this fractional reproducing kernel space, a class of fractional integro‐differential equations with a weakly singular kernel is solved. The error estimation is given. The final numerical experiments demonstrate the correctness of the theory and the effectiveness of the method.
Metabolic Regulation of Methionine Restriction in Diabetes
Authors: Yin Jie , Ren Wenkai , Chen Shuai , Li Yuying , Han Hui , Gao Jing , Liu Gang , Wu Xin , Li Tiejun , Woo Kim Sung , Yin Yulong
Published: March 2018

Although the effects of dietary methionine restriction have been investigated in the physiology of aging and diseases related to oxidative stress, the relationship between methionine restriction (MR) and the development of metabolic disorders has not been explored extensively. This review summarizes studies of the possible involvement of dietary methionine restriction in improving insulin resistance, glucose homeostasis, oxidative stress, lipid metabolism, the pentose phosphate pathway (PPP), and inflammation, with an emphasis on the fibroblast growth factor 21 and protein phosphatase 2A signals and autophagy in diabetes. Diets deficient in methionine may be a useful nutritional strategy in patients with diabetes.
Changes in Plasma Metabolite Concentrations after a Low‐Glycemic Index Diet Intervention
Authors: Hernández‐Alonso Pablo , Giardina Simona , Cañueto Daniel , Salas‐Salvadó Jordi , Cañellas Nicolau , Bulló Mònica
Published: March 2018

Scope

To examine whether a low‐glycemic index (LGI) diet improves a set of plasma metabolites related to different metabolic diseases, and comparison to a high‐glycemic index (HGI) diet and a low‐fat (LF) diet.

Methods and results

A parallel, randomized trial with three intervention diets: an LGI diet, an HGI diet, and an LF diet. A total of 122 adult overweight and obese subjects were enrolled in the study for 6 months. Blood samples were collected at baseline and at the end of the intervention. The plasma metabolomic profile of 102 subjects was analyzed using three different approaches: GC/quadrupole‐TOF, LC/quadrupole‐TOF, and nuclear magnetic resonance. Both univariate and multivariate analysis were performed. Serine levels were significantly higher following the LGI diet compared to both the HGI and LF diets (q = 0.002), whereas leucine (q = 0.015) and valine (q = 0.024) were lower in the LGI diet compared to the LF diet. A set of two sphingomyelins, two lysophosphatidylcholines, and six phosphatidylcholines were significantly modulated after the LGI diet compared to the HGI and LF diets (q < 0.05). Significant correlations between changes in plasma amino acids and lipid species with changes in body weight, glucose, insulin, and some inflammatory markers are also reported.

Conclusion

These results suggest that an LGI diet modulates certain circulating amino acids and lipid levels. These findings may explain the health benefits attributed to LGI diets in metabolic diseases such as type 2 diabetes.
Deep nets vs expert designed features in medical physics: An IMRT QA case study
Authors: Interian Yannet , Rideout Vincent , Kearney Vasant P. , Gennatas Efstathios , Morin Olivier , Cheung Joey , Solberg Timothy , Valdes Gilmer
Published: March 2018

Purpose

The purpose of this study was to compare the performance of Deep Neural Networks against a technique designed by domain experts in the prediction of gamma passing rates for Intensity Modulated Radiation Therapy Quality Assurance (IMRT QA).

Method

A total of 498 IMRT plans across all treatment sites were planned in Eclipse version 11 and delivered using a dynamic sliding window technique on Clinac iX or TrueBeam Linacs. Measurements were performed using a commercial 2D diode array, and passing rates for 3%/3 mm local dose/distance‐to‐agreement (DTA) were recorded. Separately, fluence maps calculated for each plan were used as inputs to a convolution neural network (CNN). The CNNs were trained to predict IMRT QA gamma passing rates using TensorFlow and Keras. A set of model architectures, inspired by the convolutional blocks of the VGG‐16 ImageNet model, were constructed and implemented. Synthetic data, created by rotating and translating the fluence maps during training, was created to boost the performance of the CNNs. Dropout, batch normalization, and data augmentation were utilized to help train the model. The performance of the CNNs was compared to a generalized Poisson regression model, previously developed for this application, which used 78 expert designed features.

Results

Deep Neural Networks without domain knowledge achieved comparable performance to a baseline system designed by domain experts in the prediction of 3%/3 mm Local gamma passing rates. An ensemble of neural nets resulted in a mean absolute error (MAE) of 0.70 ± 0.05 and the domain expert model resulted in a 0.74 ± 0.06.

Conclusions

Convolutional neural networks (CNNs) with transfer learning can predict IMRT QA passing rates by automatically designing features from the fluence maps without human expert supervision. Predictions from CNNs are comparable to a system carefully designed by physicist experts.
Observation of untoward 3Jcc correlations in 1,1‐ADEQUATE spectra of pyrimidine analogs: Avoiding potential interpretation pitfalls
Authors: Kim Hai‐Young , Saurí Josep , Cohen Ryan D. , Martin Gary E.
Published: March 2018

Recently, it has been reported that large nJCC correlations can sometimes be observed in 1,1‐ADEQUATE spectra with significant intensity, which opens the possibility of structural misassignment. In this work, we have focused on pyrimidine‐based compounds, which exhibit multiple bond correlations in the 1,1‐ADEQUATE experiment as a consequence of 3JCC coupling constants greater than 10 Hz. Results are supported by both the experimental measurement of 3JCC coupling constants in question using J‐modulated‐ADEQUATE and density functional theory calculations.
Wireless implantable coil with parametric amplification for in vivo electron paramagnetic resonance oximetric applications
Authors: Enomoto Ayano , Qian Chunqi , Devasahayam Nallathamby , Kishimoto Shun , Oshima Nobu , Blackman Burchelle , Swenson Rolf E. , Mitchell James B. , Koretsky Alan P. , Krishna Murali C.
Published: March 2018

Purpose

To develop an implantable wireless coil with parametric amplification capabilities for time‐domain electron paramagnetic resonance (EPR) spectroscopy operating at 300 MHz.

Methods

The wireless coil and lithium phthalocyanine (LiPc), a solid paramagnetic probe, were each embedded individually in a biocompatible polymer polydimethoxysiloxane (PDMS). EPR signals from the LiPc embedded in PDMS (LiPc/PDMS) were generated by a transmit–receive surface coil tuned to 300 MHz. Parametric amplification was configured with an external pumping coil tuned to 600 MHz and placed between the surface coil resonator and the wireless coil.

Results

Phantom studies showed significant enhancement in signal to noise using the pumping coil. However, no influence of the pumping coil on the oxygen‐dependent EPR spectral linewidth of LiPc/PDMS was observed, suggesting the validity of parametric amplification of EPR signals for oximetry by implantation of the encapsulated wireless coil and LiPc/PDMS in deep regions of live objects. In vivo studies demonstrate the feasibility of this approach to longitudinally monitor tissue pO2 in vivo and also monitor acute changes in response to pharmacologic challenges. The encapsulated wireless coil and LiPc/PDMS engendered no host immune response when implanted for ∼3 weeks and were found to be well tolerated.

Conclusions

This approach may find applications for monitoring tissue oxygenation to better understand the pathophysiology associated with wound healing, organ transplantation, and ischemic diseases.
High‐resolution whole‐brain diffusion MRI at 7T using radiofrequency parallel transmission
Authors: Wu Xiaoping , Auerbach Edward J. , Vu An T. , Moeller Steen , Lenglet Christophe , Schmitter Sebastian , Van de Moortele Pierre‐François , Yacoub Essa , Uğurbil Kâmil
Published: March 2018

Purpose

Investigating the utility of RF parallel transmission (pTx) for Human Connectome Project (HCP)‐style whole‐brain diffusion MRI (dMRI) data at 7 Tesla (7T).

Methods

Healthy subjects were scanned in pTx and single‐transmit (1Tx) modes. Multiband (MB), single‐spoke pTx pulses were designed to image sagittal slices. HCP‐style dMRI data (i.e., 1.05‐mm resolutions, MB2, b‐values = 1000/2000 s/mm2, 286 images and 40‐min scan) and data with higher accelerations (MB3 and MB4) were acquired with pTx.

Results

pTx significantly improved flip‐angle detected signal uniformity across the brain, yielding ∼19% increase in temporal SNR (tSNR) averaged over the brain relative to 1Tx. This allowed significantly enhanced estimation of multiple fiber orientations (with ∼21% decrease in dispersion) in HCP‐style 7T dMRI datasets. Additionally, pTx pulses achieved substantially lower power deposition, permitting higher accelerations, enabling collection of the same data in 2/3 and 1/2 the scan time or of more data in the same scan time.

Conclusion

pTx provides a solution to two major limitations for slice‐accelerated high‐resolution whole‐brain dMRI at 7T; it improves flip‐angle uniformity, and enables higher slice acceleration relative to current state‐of‐the‐art. As such, pTx provides significant advantages for rapid acquisition of high‐quality, high‐resolution truly whole‐brain dMRI data.