bluuebunny/crossref_metadata_2025 huggingface dataset:
Seismic lines in the boreal and arctic ecosystems of North America: environmental impacts, challenges, and opportunities
Authors: Dabros Anna , Pyper Matthew , Castilla Guillermo
Published: February 2018

The oil and gas industry has grown significantly throughout the boreal and arctic ecosystems of North America. A major feature of the ecological footprint of oil and gas exploration is seismic lines—narrow corridors used to transport and deploy geophysical survey equipment. These lines, which traverse forests, tundra, uplands, and peatlands, were historically up to 10 m wide. Over the past decade, seismic lines have decreased in width (in some cases down to 1.75–3 m); however, their density has increased drastically and their construction is expected to continue in regions of Canada and the United States that are rich in oil and gas resources. We examine the literature related to the environmental impacts of, and restoration and reclamation efforts associated with, seismic lines in the boreal and arctic ecosystems of North America. With respect to conventional seismic lines, numerous studies report significant and persistent environmental changes along these lines and slow recovery of vegetation that translates into a lasting fragmentation of the landscape. This fragmentation has many ramifications for biodiversity and ecosystem processes, including significant implications for threatened woodland caribou herds. While modern, low-impact seismic lines have comparatively lower ecological effects at the site-level, their high density and associated potential edge effects suggest that their actual environmental impact may be underestimated. Seismic line restoration is a critical aspect of future integrated landscape management in hydrocarbon-rich regions of the boreal-arctic, and if widely applied, has the potential to benefit a wide range of species and maintain or re-establish key ecosystem services such as carbon sequestration and biodiversity.
Photophysical and photochemical properties of fluoroether-substituted zinc(II) and titanium(IV) phthalocyanines
Authors: Gürol İlke , Gümüş Gülay , Tarakci Deniz Kutlu , Güngör Ömer , Durmuş Mahmut , Ahsen Vefa
Published: February 2018

The synthesis and characterization of novel zinc(II) (1a–4a) and oxo-titanium(IV) (1b–4b) phthalocyanine derivatives bearing 1H,1H-nona?uoro-3,6-dioxaheptan-1-ol groups are described for the first time. These phthalocyanines (1a–4a and 1b–4b) were characterized by elemental analysis and different spectroscopic techniques such as UV-vis, [Formula: see text]H NMR, FTIR and mass. Furthermore, the photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen generation and photodegradation) properties of these phthalocyanines were investigated in tetrahydrofuran (THF) solution. The influence of the number of the substituted groups (tetra or octa), position of the substituents (peripheral or non-peripheral) and central metal atom (zinc or titanium) on the photophysical and photochemical properties of these phthalocyanines were evaluated.
Fine-Grained Access Control via Policy-Carrying Data
Authors: Padget Julian A. , Vasconcelos Wamberto W.
Published: February 2018

We address the problem of associating access policies with datasets and how to monitor compliance via policy-carrying data. Our contributions are a formal model in first-order logic inspired by normative multi-agent systems to regulate data access, and a computational model for the validation of specific use cases and the verification of policies against criteria. Existing work on access policy identifies roles as a key enabler, with which we concur, but much of the rest focusses on authentication and authorization technology. Our proposal aims to address the normative principles put forward in Berners-Lee’s bill of rights for the internet, through human-readable but machine-processable access control policies.
Participatory Design and Participatory Research
Authors: Duarte Ana Maria Bustamante , Brendel Nina , Degbelo Auriol , Kray Christian
Published: February 2018

Participatory design (PD) in HCI has been successfully applied to vulnerable groups, but further research is still needed on forced migrants. We report on a month-long case study with a group of about 25 young forced migrants (YFMs), where we applied and adapted strategies from PD and participatory research (PR). We gained insights into the benefits and drawbacks of combining PD and PR concepts in this particular scenario. The PD+PR approach supported intercultural collaborations between YFMs and young members of the host community. It also enabled communication across language barriers by using visual and “didactic reduction” resources. On a theoretical level, the experiences we gained allowed us to reflect on the role of “safe spaces” for participation and the need for further discussing it in PD. Our results can benefit researchers who take part in technology-related participatory processes with YFMs.
Exploiting User and Venue Characteristics for Fine-Grained Tweet Geolocation
Authors: Chong Wen-Haw , Lim Ee-Peng
Published: February 2018

Which venue is a tweet posted from? We call this a fine-grained geolocation problem. Given an observed tweet, the task is to infer its discrete posting venue, e.g., a specific restaurant. This recovers the venue context and differs from prior work, which geolocats tweets to location coordinates or cities/neighborhoods.

First, we conduct empirical analysis to uncover venue and user characteristics for improving geolocation. For venues, we observe
spatial homophily
, in which venues near each other have more similar tweet content (i.e., text representations) compared to venues further apart. For users, we observe that they are
spatially focused
and more likely to visit venues near their previous visits. We also find that a substantial proportion of users post one or more geocoded tweet(s), thus providing their location history data. We then propose geolocation models that exploit spatial homophily and spatial focus characteristics plus posting time information. Our models rank candidate venues of test tweets such that the actual posting venue is ranked high. To better tune model parameters, we introduce a learning-to-rank framework. Our best model significantly outperforms state-of-the-art baselines. Furthermore, we show that tweets without any location-indicative words can be geolocated meaningfully as well.
A Comparative Study of Predictable DRAM Controllers
Authors: Guo Danlu , Hassan Mohamed , Pellizzoni Rodolfo , Patel Hiren
Published: February 2018

Recently, the research community has introduced several predictable dynamic random-access memory (DRAM) controller designs that provide improved worst-case timing guarantees for real-time embedded systems. The proposed controllers significantly differ in terms of arbitration, configuration, and simulation environment, making it difficult to assess the contribution of each approach. To bridge this gap, this article provides the first comprehensive evaluation of state-of-the-art predictable DRAM controllers. We propose a categorization of available controllers, and introduce an analytical performance model based on worst-case latency. We then conduct an extensive evaluation for all state-of-the-art controllers based on a common simulation platform, and discuss findings and recommendations.
Explicit Diversification of Event Aspects for Temporal Summarization
Authors: McCreadie Richard , Santos Rodrygo L. T. , Macdonald Craig , Ounis Iadh
Published: February 2018

During major events, such as emergencies and disasters, a large volume of information is reported on newswire and social media platforms. Temporal summarization (TS) approaches are used to automatically produce concise overviews of such events by extracting text snippets from related articles over time. Current TS approaches rely on a combination of event relevance and textual novelty for snippet selection. However, for events that span multiple days, textual novelty is often a poor criterion for selecting snippets, since many snippets are textually unique but are semantically redundant or non-informative. In this article, we propose a framework for the diversification of snippets using explicit event aspects, building on recent works in search result diversification. In particular, we first propose two techniques to identify explicit aspects that a user might want to see covered in a summary for different types of event. We then extend a state-of-the-art explicit diversification framework to maximize the coverage of these aspects when selecting summary snippets for unseen events. Through experimentation over the TREC TS 2013, 2014, and 2015 datasets, we show that explicit diversification for temporal summarization significantly outperforms classical novelty-based diversification, as the use of explicit event aspects reduces the amount of redundant and off-topic snippets returned, while also increasing summary timeliness.
Quasi-matrix-free Hybrid Multigrid on Dynamically Adaptive Cartesian Grids
Authors: Weinzierl Marion , Weinzierl Tobias
Published: February 2018

We present a family of spacetree-based multigrid realizations using the tree’s multiscale nature to derive coarse grids. They align with matrix-free geometric multigrid solvers as they never assemble the system matrices, which is cumbersome for dynamically adaptive grids and full multigrid. The most sophisticated realizations use BoxMG to construct operator-dependent prolongation and restriction in combination with Galerkin/Petrov-Galerkin coarse-grid operators. This yields robust solvers for nontrivial elliptic problems. We embed the algebraic, problem-dependent, and grid-dependent multigrid operators as stencils into the grid and evaluate all matrix-vector productsin situthroughout the grid traversals. Such an approach is not literally matrix-free as the grid carries the matrix. We propose to switch to a hierarchical representation of all operators. Only differences of algebraic operators to their geometric counterparts are held. These hierarchical differences can be stored and exchanged with small memory footprint. Our realizations support arbitrary dynamically adaptive grids while they vertically integrate the multilevel operations through spacetree linearization. This yields good memory access characteristics, while standard colouring of mesh entities with domain decomposition allows us to use parallel many-core clusters. All realization ingredients are detailed such that they can be used by other codes.
Localizing Optic Disc in Retinal Image Automatically with Entropy Based Algorithm
Authors: Muhammed Lamia AbedNoor
Published: February 2018

Examining retinal image continuously plays an important role in determining human eye health; with any variation present in this image, it may be resulting from some disease. Therefore, there is a need for computer-aided scanning for retinal image to perform this task automatically and accurately. The fundamental step in this task is identification of the retina elements; optical disk localization is the most important one in this identification. Different optical disc localization algorithms have been suggested, such as an algorithm that would be proposed in this paper. The assumption is based on the fact that optical disc area has rich information, so its entropy value is more significant in this area. The suggested algorithm has recursive steps for testing the entropy of different patches in image; sliding window technique is used to get these patches in a specific way. The results of practical work were obtained using different common data set, which achieved good accuracy in trivial computation time. Finally, this paper consists of four sections: a section for introduction containing the related works, a section for methodology and material, a section for practical work with results, and a section for conclusion.
Liver Illness and Psoriatic Patients
Authors: Fiore Marco , Leone Sebastiano , Maraolo Alberto Enrico , Berti Emilio , Damiani Giovanni
Published: February 2018

Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world’s population. Systemic treatments, including methotrexate and cyclosporin, are associated with potential hepatotoxicity, due to either direct liver damage or immunosuppression or both immunomediated and a direct liver injury; therefore, treatment of patients with psoriasis poses a therapeutic challenge. The aim of this minireview is to help clinicians in the management of psoriatic patients who develop signs of liver dysfunction. To find relevant articles, a comprehensive search was performed on PubMed, EMBASE, and Cochrane with appropriate combinations of the following keywords being considered: viral hepatitis, nonalcoholic fatty liver disease, psoriasis, hepatotoxicity, drug toxicity, cholestasis, and autoimmune liver diseases.
Genesis of Clastic Dykes and Soft-Sediment Deformation Structures in the Mamfe Basin, South-West Region, Cameroon: Field Geology Approach
Authors: Ekoko Eric Bokanda , Emile Ekomane , John Takem Eyong , Isaac Konfor Njilah , Ethel Nkongho Ashukem , Rita Ndige Bisong , Salomon Bertrant Bisse
Published: February 2018

This paper aims to investigate the genesis of clastic dykes and soft-sediment deformation structures in the Mamfe Basin, South West-Region, Cameroon. Results from this study portray the following: (1) The clastic dykes are extrusive and were generated from preexisting soft-sediments that penetrate fissures caused by seismic activity. It can be concluded that clastic dykes originate from seismic shacking, probably induced by volcanic-tectonic activity and magmatic dykes that cut across the Precambrian and Cretaceous formations of the Mamfe Basin. (2) The soft-sediment deformation structures (flexures, sheared foliations, anticlinal folds, load casts, and flame structures) are likely triggered by seismic shocks. The inferred influence of seismic activity results from rifting and rapid subsidence of basin-fill during the Cretaceous. Some of these soft-sediment deformation structures (SSDS) are induced by fluidization and liquefaction triggered by rapid sedimentation within tectonically active settings, as well as density variations illustrated by local occurrence of load casts with weak lateral extensions. (3) The synsedimentary features (joints, faults, filled fractures) are related to local stress triggered by gravitational sliding, because the fractures were filled by unconsolidated clastic materials.
Anatomical Retinal Changes after Photodynamic Therapy in Chronic Central Serous Chorioretinopathy
Authors: Ruiz-del-Tiempo María Pilar , Calvo Pilar , Ferreras Antonio , Leciñena Jesús , Pablo Luis , Ruiz-Moreno Oscar
Published: February 2018

Purpose. To evaluate anatomical retinal changes measured by spectral-domain optical coherence tomography (SD-OCT), after applying photodynamic therapy (PDT) for treatment of chronic central serous chorioretinopathy (CSC). Methods. A retrospective analysis was conducted on 43 patients (48 eyes) with chronic CSC treated with PDT. Visual acuity (VA), central retinal thickness (CRT), outer nuclear layer (ONL) thickness, subretinal fluid (SRF), and photoreceptor ellipsoid zone (EZ) measured by SD-OCT were collected at baseline and at 3, 6, and 12 months after PDT. Differences between normally distributed variables were calculated by a paired-sample t-test; p<0.05 was considered statistically significant. Results. Mean age was 50 ± 9.8 years. Mean time from diagnosis to PDT was 12.5 months. Baseline VA was 0.51 ± 0.24 and significantly improved (p<0.001) to 0.74 ± 0.26 one year after PDT. CRT and SRF significantly decreased (p<0.001) at 3, 6, and 12 months after treatment. ONL thickness and EZ did not significantly change at any point during follow-up. Conclusions. Not significant changes were found in the ONL or EZ 12 months after PDT.
Implantation of Neuronal Stem Cells Enhances Object Recognition without Increasing Neurogenesis after Lateral Fluid Percussion Injury in Mice
Authors: Ngwenya Laura B. , Mazumder Sarmistha , Porter Zachary R. , Minnema Amy , Oswald Duane J. , Farhadi H. Francis
Published: February 2018

Cognitive deficits after traumatic brain injury (TBI) are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI) in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC). Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation.
Calbindin-D28k in the Brain Influences the Expression of Cellular Prion Protein
Authors: Yoo Yeong-Min , Jeung Eui-Bae
Published: February 2018

The phenotypes of calbindin-D9k‐ (CaBP-9k‐) knockout (KO), calbindin‐D28k‐ (CaBP-28k‐) KO, and CaBP-9k/28k‐KO mice are similar to those of wild‐type (WT) mice due to the compensatory action of other calcium transport proteins. In this study, we investigated the expression of cellular prion protein (PrPC) in the brains of CaBP-9k‐, CaBP-28k‐, and CaBP-9k/28k‐KO mice. PrPC expression was significantly upregulated in the brain of all three strains. Levels of phospho‐Akt (Ser473) and phospho‐Bad (Ser136) were significantly elevated, but those of phospho‐ERK and phospho‐Bad (Ser155 and 112) were significantly reduced in the brains of CaBP-9k‐, CaBP-28k‐, and CaBP-9k/28k‐KO mice. The expressions of the Bcl‐2, p53, Bax, Cu/Zn‐SOD, and Mn‐SOD proteins were decreased in the brains of all KO mice. Expression of the endoplasmic reticulum marker protein BiP/GRP78 was decreased, and that of the CHOP protein was increased in the brains of those KO mice. To identify the roles of CaBP-28k, we transfected PC12 cells with siRNA for CaBP-28k and found increased expression of the PrPC protein compared to the levels in control cells. These results suggest that CaBP-28k expression may regulate PrPC protein expression and these mice may be vulnerable to the influence of prion disease.
A Pervasive Approach to EEG‐Based Depression Detection
Authors: Cai Hanshu , Han Jiashuo , Chen Yunfei , Sha Xiaocong , Wang Ziyang , Hu Bin , Yang Jing , Feng Lei , Ding Zhijie , Chen Yiqiang , Gutknecht Jürg
Published: February 2018

Nowadays, depression is the world’s major health concern and economic burden worldwide. However, due to the limitations of current methods for depression diagnosis, a pervasive and objective approach is essential. In the present study, a psychophysiological database, containing 213 (92 depressed patients and 121 normal controls) subjects, was constructed. The electroencephalogram (EEG) signals of all participants under resting state and sound stimulation were collected using a pervasive prefrontal‐lobe three‐electrode EEG system at Fp1, Fp2, and Fpz electrode sites. After denoising using the Finite Impulse Response filter combining the Kalman derivation formula, Discrete Wavelet Transformation, and an Adaptive Predictor Filter, a total of 270 linear and nonlinear features were extracted. Then, the minimal‐redundancy‐maximal‐relevance feature selection technique reduced the dimensionality of the feature space. Four classification methods (Support Vector Machine, K‐Nearest Neighbor, Classification Trees, and Artificial Neural Network) distinguished the depressed participants from normal controls. The classifiers’ performances were evaluated using 10‐fold cross‐validation. The results showed that K‐Nearest Neighbor (KNN) had the highest accuracy of 79.27%. The result also suggested that the absolute power of the theta wave might be a valid characteristic for discriminating depression. This study proves the feasibility of a pervasive three‐electrode EEG acquisition system for depression diagnosis.
Numerical Investigation of Water Entry Problem of Pounders with Different Geometric Shapes and Drop Heights for Dynamic Compaction of the Seabed
Authors: Taghizadeh Valdi Mohammad Hossein , Atrechian Mohammad Reza , Jafary Shalkoohy Ata , Chavoshi Elham
Published: February 2018

The water entry problem of three-dimensional pounders with different geometric shapes of cube, cylinder, sphere, pyramid, and cone was numerically simulated by the commercial software Abaqus, and the effects of pounder shape and drop height from the free surface of water on deepwater displacement and velocity as well as pinch-off time and depth were investigated. An explicit dynamic analysis method was employed to model fluid-structure interactions using a Coupled Eulerian-Lagrangian (CEL) formulation. The simulation results are verified by showing the computed shape of the air cavity, displacement of sphere, pinch-off time, and depth which all agreed with the experimental results. The results reveal that the drag force of water has the highest and lowest effect on cubical and conical pounders, respectively. Increasing the pounder drop height up to the critical height leads to increased pounder velocity while impacting the model bed and more than the critical drop height has a reverse effect on pounder impact velocity. Pinch-off time is a very weak function of pounder impact velocity; but pinch-off depth increases linearly with increased impact velocity.
Subchronic and Genetic Safety Assessment of a New Medicinal Dendrobium Species: Dendrobium Taiseed Tosnobile in Rats
Authors: Yang Li-Chan , Liao Jiunn-Wang , Wen Chi-Luan , Lin Wen-Chuan
Published: February 2018

Dendrobium Taiseed Tosnobile is a new species of herba dendrobii (Shi‐Hu) that was developed by crossbreeding D. tosaense and D. nobile. Its pharmacological activity and active component have been reported, but its subchronic toxicity and genetic safety have not yet been investigated. This study assessed the 90‐day oral toxicity and genetic safety of the aqueous extracts of D. Taiseed Tosnobile (DTTE) in male and female Sprague‐Dawley (SD) rats. Eighty rats were divided into four groups, each consisting of ten male and ten female rats. DTTE was given orally to rats at 800, 1600, or 2400 mg/kg for 90 consecutive days, and distilled water was used for the control group. Genotoxicity studies were performed using a bacterial reverse mutation assay and in vivo mammalian cell micronucleus test in ICR mice and analyzed using flow cytometry. Throughout the study period, no abnormal changes were observed in clinical signs and body weight or on ophthalmological examinations. Additionally, no significant differences were found in urinalysis, hematology, and serum biochemistry parameters between the treatment and control groups. Necropsy and histopathological examination indicated no treatment‐related changes. Based on results, the no‐observed‐adverse‐effect level of DTTE is greater than 2400 mg/kg in SD rats.
Amyloid-Beta Radiotracer [18F]BF-227 Does Not Bind to Cytoplasmic Glial Inclusions of Postmortem Multiple System Atrophy Brain Tissue
Authors: Verdurand Mathieu , Levigoureux Elise , Lancelot Sophie , Zeinyeh Waël , Billard Thierry , Quadrio Isabelle , Perret-Liaudet Armand , Zimmer Luc , Chauveau Fabien
Published: February 2018

The accumulation of aggregated alpha-synuclein (α-syn) in multiple brain regions is a neuropathological hallmark of synucleinopathies. Multiple system atrophy (MSA) is a synucleinopathy characterized by the predominant cerebral accumulation of aggregated α-syn as cytoplasmic glial inclusions (CGI). A premortem diagnosis tool would improve early diagnosis and help monitoring disease progression and therapeutic efficacy. One Positron Emission Tomography (PET) study suggested [11C]BF-227 as a promising radiotracer for monitoring intracellular α-syn deposition in MSA patients. We sought to confirm the binding of this radiotracer to α-syn using state-of-the-art autoradiography. Medulla sections were obtained from 9 MSA patients and 9 controls (London Neurodegenerative Diseases Brain Bank). [18F]BF-227, chemically identical to [11C]BF-227, was used at nanomolar concentrations to perform in vitro autoradiography assays. Autoradiograms were superimposed on fluorescent staining from the conformational anti-α-syn antibody 5G4 and quantified after immunofluorescence-driven definition of regions of interest. Autoradiography showed no specific signals in MSA patients in comparison to controls despite widespread pathology detected by immunofluorescence. Autoradiography does not support a significant binding of [18F]BF-227 to CGI at concentrations typically achieved in PET experiments.
Levels of Urinary Trypsin Inhibitor and Structure of Its Chondroitin Sulphate Moiety in Type 1 and Type 2 Diabetes
Authors: Lepedda Antonio Junior , Nieddu Gabriele , Rocchiccioli Silvia , Ucciferri Nadia , Idini Michela , De Muro Pierina , Formato Marilena
Published: February 2018

Background. Diabetes mellitus is a global health problem representing the fifth leading cause of mortality and a major risk factor for cardiovascular diseases. In the last years, we reported an association among urinary trypsin inhibitor (UTI), a small proteoglycan that plays pleiotropic roles in many inflammatory processes, and both type 1 and 2 diabetes and developed a method for its direct quantitation and structural characterization.Methods. Urine from 39 patients affected by type 1 diabetes, 32 patients with type 2 diabetes, and 52 controls were analysed. UTI was separated from the main glycosaminoglycans physiologically present in urine by anion exchange chromatography, treated for chondroitin sulphate (CS) chain complete depolymerisation, and analysed for both UTI content and CS structure. UTI identification was performed by nano-LC-MS/MS analysis.Results. We evidenced increased UTI levels, as well as reduced sulphation of its CS moiety in association with diabetes, regardless of both age and medium-term glycaemic control. Furthermore, no association between UTI and albumin excretion rate was found.Conclusions. Evidences suggest that UTI levels are not directly correlated with renal function or, otherwise, that they may increase before the onset of renal impairment in diabetes, representing a potential marker for the underlying inflammatory condition.
Expression of Adipocyte/Macrophage Fatty Acid–Binding Protein in Tumor-Associated Macrophages Promotes Breast Cancer Progression
Authors: Hao Jiaqing , Yan Fei , Zhang Yuwen , Triplett Ashley , Zhang Ying , Schultz Debra A. , Sun Yanwen , Zeng Jun , Silverstein Kevin A.T. , Zheng Qi , Bernlohr David A. , Cleary Margot P. , Egilmez Nejat K. , Sauter Edward , Liu Shujun , Suttles Jill , Li Bing
Published: February 2018

Tumor-associated macrophages (TAM) play a critical role in cancer development and progression. However, the heterogeneity of TAM presents a major challenge to identify clinically relevant markers for protumor TAM. Here, we report that expression of adipocyte/macrophage fatty acid–binding protein (A-FABP) in TAM promotes breast cancer progression. Although upregulation of A-FABP was inversely associated with breast cancer survival, deficiency of A-FABP significantly reduced mammary tumor growth and metastasis. Furthermore, the protumor effect of A-FABP was mediated by TAM, in particular, in a subset of TAM with a CD11b+F4/80+MHCII−Ly6C− phenotype. A-FABP expression in TAM facilitated protumor IL6/STAT3 signaling through regulation of the NFκB/miR-29b pathway. Collectively, our results suggest A-FABP as a new functional marker for protumor TAM.

Significance: These findings identify A-FABP as a functional marker for protumor macrophages, thus offering a new target for tumor immunotherapy. Cancer Res; 78(9); 2343–55. ©2018 AACR.
Prediction of Chemotherapeutic Efficacy in Non–Small Cell Lung Cancer by Serum Metabolomic Profiling
Authors: Tian Yanhua , Wang Zhijie , Liu Xiaohui , Duan Jianchun , Feng Guoshuang , Yin Yuxin , Gu Jin , Chen Zhaoli , Gao Shugeng , Bai Hua , Wan Rui , Jiang Jun , Liu Jia , Zhang Cong , Wang Di , Han Jiefei , Zhang Xue , Cai Liangliang , He Jie , Wang Jie
Published: February 2018

Purpose: No validated biomarkers that could identify the subset of patients with lung adenocarcinoma who might benefit from chemotherapy have yet been well established. This study aimed to explore potential biomarker model predictive of efficacy and survival outcomes after first-line pemetrexed plus platinum doublet based on metabolomics profiling.

Experimental Design: In total, 354 consecutive eligible patients were assigned to receive first-line chemotherapy of pemetrexed in combination with either cisplatin or carboplatin. Prospectively collected serum samples before initial treatment were utilized to perform metabolomics profiling analyses under the application of LC/MS-MS. Binary logistic regression analysis was carried out to establish discrimination models.

Results: There were 251 cases randomly sorted into discovery set, the rest of 103 cases into validation set. Seven metabolites including hypotaurine, uridine, dodecanoylcarnitine, choline, dimethylglycine, niacinamide, and l-palmitoylcarnitine were identified associated with chemo response. On the basis of the seven-metabolite panel, a discriminant model according to logistic regression values g(z) was established with the receiver operating characteristic curve (AUC) of 0.912 (Discovery set) and 0.909 (Validation set) in differentiating progressive disease (PD) groups from disease control (DC) groups. The median progression-free survival (PFS) after chemotherapy in patients with g(z) ≤0.155 was significantly longer than that in those with g(z) > 0.155 (10.3 vs.4.5 months, P < 0.001).

Conclusions: This study developed an effective and convenient discriminant model that can accurately predict the efficacy and survival outcomes of pemetrexed plus platinum doublet chemotherapy prior to treatment delivery. Clin Cancer Res; 24(9); 2100–9. ©2018 AACR.
Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?
Authors: Kabraji Sheheryar , Ni Jing , Lin Nancy U. , Xie Shaozhen , Winer Eric P. , Zhao Jean J.
Published: February 2018

The brain is the most common site of first metastasis for patients with HER2-positive breast cancer treated with HER2-targeting drugs. However, the development of effective therapies for breast cancer brain metastases (BCBM) is limited by an incomplete understanding of the mechanisms governing drug sensitivity in the central nervous system. Pharmacodynamic data from patients and in vivo models suggest that inadequate drug penetration across the “blood–tumor” barrier is not the whole story. Using HER2-positive BCBMs as a case study, we highlight recent data from orthotopic brain metastasis models that implicate brain-specific drug resistance mechanisms in BCBMs and suggest a translational research paradigm to guide drug development for treatment of BCBMs. Clin Cancer Res; 24(8); 1795–804. ©2018 AACR.
Palliativversorgung ist immer individuell
Authors: Lübbe Andreas Stephan
Published: February 2018

Background: The aim of this study was to compare the characteristics for genitourinary cancer (GUC) patients receiving specialized inpatient palliative care (SIPC) with those of a general cohort. Methods: We retrospectively evaluated 151 GUC patients receiving SIPC from 2008 to 2014 regarding symptoms, problems, treatment, and outcome. These characteristics were compared with a general cohort of 1,285 patients with various diseases who received SIPC (German Hospice and Palliative care investigation: HOPE). Results: Patients suffering from advanced prostate cancer (n = 59), renal cell cancer (n = 37), urothelial cancer (n = 36), urothelial accompanied by prostate cancer (n = 11), germ cell cancer (n = 7), and penile squamous cell cancer (n = 1) were included in the study. Most frequent symptoms and problems at admission were weakness (93%), the need for assistance with activities of daily living (85%), loss of appetite (81%), and organization of care (80%). Symptoms were more frequent in the GUC than in the general cohort during treatment, in particular with regards to pain (p < 0.001), tension (p < 0.001), nausea (p = 0.001), and vomiting (p < 0.001). GUC patients received significantly more opioids with 89% compared to the general cohort with 72% (p < 0.001). Conclusion: Symptom burden of GUC patients, in particular pain, tension, and nausea was higher compared to the general cohort, and analgesic treatment played an important role in achieving control of symptoms.
Prognoseabschätzung bei Multiplem Myelom
Authors: Lutz Raphael
Published: February 2018

Background: The Revised International Staging System (R-ISS) has recently been introduced as a comprehensive prognostic score for multiple myeloma (MM). Validation of the R-ISS in patients treated outside of clinical trials is the focus of current investigations. The aim of this study was to test the prognostic role of the R-ISS in MM patients ineligible for autologous stem cell transplantation. Patients and Methods: A total of 102 newly diagnosed MM patients were analyzed. All patients were initially treated with thalidomide-based combinations. Results: An overall response rate was achieved in 77.4% patients. Both the International Staging System (ISS) and the R-ISS influenced the event-free survival and the overall survival (OS). However, the ISS was unable to discriminate patients in stages ISS1 and ISS2 regarding OS. On the contrary, the R-ISS clearly differentiated risk categories regarding OS and provided an improved discriminative power of 6.3% compared to the ISS. Furthermore, among the parameters that were significant in univariate analysis (presence of renal impairment, anemia, platelet count < 130 × 109/l, and R-ISS), the multivariate model pointed to the R-ISS (p = 0.001) as the most important parameter influencing OS. Conclusion: The R-ISS represents a useful tool for risk stratification of transplant-ineligible MM patients and should be considered as a prognostic index in daily clinical practice.
Robot-Assisted Transplant Surgery - Vision or Reality A Comprehensive Review
Authors: Stiegler Philipp , Schemmer Peter
Published: February 2018

Minimally invasive surgery is standard procedure for many operations. Further refinements include the introduction of robotic surgery which is still an emerging field especially in laparoscopic surgery. Since the successful introduction of the da Vinci Robotic Surgical System, the robotic approach in organ transplantation has become of great interest in both the live donor organ retrieval and the recipient operation. Robotic surgery for kidney, liver, and pancreas transplantation is feasible. Over 700 donor nephrectomies and 100 kidney transplantations have been performed already, and robotic surgery is standard in a small number of pioneer centers; however, larger series and most importantly randomized controlled trials for the highest evidence are needed. Longer warm ischemia time and higher costs limit these procedures at the moment.
Study Time after School and Habitual Eating Are Associated with Risk for Obesity among Overweight Korean Children: A Prospective Study
Authors: Lee Eun Young , Kang Borami , Yang Yeoree , Yang Hae Kyung , Kim Hun-Sung , Lim Sun-Young , Lee Jin-Hee , Lee Seong-Su , Suh Byung-Kyu , Yoon Kun-Ho
Published: February 2018

Objective: To investigate behavioral factors that contribute to the development of obesity among overweight children. Methods: Among a community sample of 884 children aged 9-13 years, 833 children completed a baseline and 1-year follow-up examination that included anthropometrics, physical fitness, and behavioral factors. Results: During the follow-up period, BMI for most children with normal weight or obesity did not change. However, among overweight children (n = 100), about one-third developed obesity (n = 26), while the others were categorized as normal weight (n = 32) or overweight (n = 42) after 1 year. Characteristics of overweight children at baseline and follow-up were analyzed. Those who developed obesity showed a notable increase in blood pressure as well as in BMI, waist circumference, and body fat over 1 year. At baseline, this group spent more time studying after school compared to overweight children who did not develop obesity, while there were no differences in time spent viewing television or engaging in vigorous physical activity. Eating outside the home, fast food consumption, and habitual eating in the absence of hunger were more common at baseline in those who did versus those who did not develop obesity. After adjusting for age, sex, and BMI, spending more time studying after school and habitual eating without hunger were associated with the development of obesity. Conclusion: Among Korean overweight children, study time after school and habitual eating without hunger were associated with an increased risk for development of obesity.
Extravascular CD3+ T Cells in Brains of Alzheimer Disease Patients Correlate with Tau but Not with Amyloid Pathology: An Immunohistochemical Study
Authors: Merlini Mario , Kirabali Tunahan , Kulic Luka , Nitsch Roger M. , Ferretti Maria Teresa
Published: February 2018

Background: Strong genetic and epidemiological evidence points to a crucial role of the immune system in the development of Alzheimer disease (AD). CD3+ T lymphocytes have been described in brains of postmortem AD patients and in transgenic models of AD-like cerebral amyloidosis and tau pathology. However, the occurrence of T cells in AD brains is still controversial; furthermore, the relationship between T cells and hallmarks of AD pathology (amyloid plaques and neurofibrillary tangles) remains to be established. Objectives: We have studied the occurrence of T cells in postmortem hippocampi and mid frontal gyrus (MFG) samples of AD patients (Braak stage V-VI) and nondemented control subjects and correlated it with amyloid and tau pathology burden. Methods: Confocal microscopy and bright-field immunohistochemistry were used to identify brain-associated T cells. Extravascular CD3+ T cells were quantified and compared to nondemented controls. In addition, numbers of extravascular CD3+ T cells were correlated with amyloid (6E10 staining) and tau pathology (AT8 staining) in the same sections. Results: Several CD3+, extravascular T cells were observed in the brains of AD patients, mostly of the CD8+ subtype. AD hippocampi harbored significantly increased numbers of extravascular CD3+ T cells compared to nondemented controls. CD3+ T cells significantly correlated with tau pathology but not with amyloid plaques in AD samples. Conclusions: Our data support the notion of T-cell occurrence in AD brains and suggest that, in advanced stages of AD, T-cell extravasation is driven by tau-related neurodegenerative changes rather than by cerebral amyloidosis. T cells could be crucial for driving the amyloid-independent phase of the AD pathology.
A Rare Multifocal Pattern of Type 2 Autoimmune Pancreatitis with Negative IgG4: A Potential Diagnostic Pitfall That May Mimic Multifocal Pancreatic Adenocarcinoma
Authors: Hota Partha , Patel Tejas , Zhao Xiaofeng , Jhala Nirag , Agosto Omar
Published: February 2018

Autoimmune pancreatitis (AIP) is an increasingly recognized form of acute pancreatitis characterized by obstructive jaundice with a rapid and dramatic treatment response to steroid therapy. Recently, AIP has been divided into two distinct phenotypes: lymphoplasmocytic sclerosing pancreatitis AIP (type 1) and idiopathic duct-centric pancreatitis AIP (type 2); each of which have their own distinct demographics, diagnostic criteria, and histopathological features. We report, to the best of our knowledge, the first case of a multifocal pattern of type 2 AIP characterized with both CT and MR imaging. This rare imaging pattern of AIP may mimic the appearance of more worrisome malignant etiologies such as multifocal pancreatic adenocarcinoma or lymphoma, with overlapping imaging characteristics potentially complicating or delaying diagnosis. Therefore, recognition of this atypical pattern of AIP and avoidance of this potential diagnostic pitfall is crucial.
Effect of bisphenol A exposure on the expressions of five ovary development related genes in the oriental river prawn, Macrobrachium nipponense (Decapoda, Palaemonidae)
Authors: Li Xiu , Zhang Fengying , Jiang Keji , Zhao Weihong , Zhao Ming , Song Wei , Ma Lingbo
Published: February 2018

The oriental river prawn,Macrobrachium nipponense, is one of the important commercial shrimp species. Recently a severe problem of precocious maturation has greatly hampered this shrimp aquaculture industry. Bisphenol A (BPA), a high-production-volume chemical substance used in the plastic manufacturing industry, has been thought of as an endocrine disruptor on the developmental processes of animals. In this study, we investigated the effect of BPA exposure on the expressions of five ovary development related genes such as Mago nashi, Tsunagi, Gustavus, Ubc9, and Von Willebrand factor D-Kazal inM. nipponense. Five concentration gradients (5.01, 7.76, 12.06, 18.62 and 28.84 mg/l) of BPA were set and the ovaries of exposed prawns were collected at different time points for expression analysis. Compared with the control group at day 19, BPA had a two-phase effect: a stimulating effect under low concentrations from 5.01 to 12.06 mg/l, whereas a negative effect was noted at high concentrations from 12.06 to 28.84 mg/l. The expression profiles under different BPA concentrations significantly changed along with the extension of exposure time. The medium concentration of BPA (12.06 mg/l) had a persistent influence on the expressions of the transcripts, while the effect was transient under the lowest concentration (5.01 mg/l). It is suggested that the concentration under 5.01 mg/l might be safe for the development ofM. nipponense, but exceeding 12.06 mg/l may be harmful. When exposed to clean fresh water without BPA, the gene expressions rebounded a little. This may indicate that the biological damage of BPA was partly reversible after the prawns had been placed in the fresh water without BPA. So the BPA pollutant concentration should be controlled at secure levels in order to ensure safety in aquaculture, in this respect. This study provides fundamental data for the relationship between BPA and precocious maturation of the prawn, and will most probably contribute to the understanding of the sexual maturation process in crustaceans.
“A Manifestation of a Deep, Inborn Inherited Instinct”: Modernist Aesthetics and the Instabilities of Inheritance in Joseph Conrad’s Lord Jim
Authors: Chan Evelyn T.Y.
Published: February 2018

This essay explores how Joseph Conrad reworks the trope of inheritance—traditionally considered relevant for earlier nineteenth-century literature rather than Modernism—in expressing Jim’s crisis of self-making inLord Jim. Conrad moves away from the conventional emphasis on familial inheritance of social status and wealth to focus on inherited abilities, which Jim tries to prove in building his heroic and gentlemanly status. However, there are limits to this process of self-creation: inheritance is, as the word’s root suggests, innate to oneself, yet can also be extrinsic since it still needs to be expressed to call it one’s own, and be unstable since it is open to interpretation. Such complexities in the notion of inheritance, the essay argues, contribute to a modernist aesthetics in the novel that simultaneously harbours continuity (such as gradualism, predictability, and succession) and discontinuity (such as narrative rupture and the breakdown of causality), allowing the perils of modern self-making to be more fully revealed.
From Freedom to Slavery
Authors: Rositani Annunziata
Published: February 2018

This article presents some reflections on slavery in the Ancient Near East during the Old Babylonian period. Particular attention is paid to an analysis of the sources for prisoners of war originating from Uruk in which the bīt asīrī, “the house of prisoners of war” is mentioned. These texts from the bīt asīrī date to the short reign of Rīm-Anum, who held power in Uruk for about eighteen months, between 1742 and 1740 BC. The use of war prisoners as labor force and slaves is examined in detail. It is suggested that the bīt asīrī was an institutional entity, managed by the state, and moreover that it was connected with the production of flour. This investigation also makes comparisons with other references to prisons in the Ancient Near East and especially in the Bible. Lastly, the ways in which war captives could be freed are discussed.
Sensitivity of Ensemble Forecast Verification to Model Bias
Authors: Wang Jingzhuo , Chen Jing , Du Jun , Zhang Yutao , Xia Yu , Deng Guo
Published: February 2018

This study demonstrates how model bias can adversely affect the quality assessment of an ensemble prediction system (EPS) by verification metrics. A regional EPS [Global and Regional Assimilation and Prediction Enhanced System-Regional Ensemble Prediction System (GRAPES-REPS)] was verified over a period of one month over China. Three variables (500-hPa and 2-m temperatures, and 250-hPa wind) are selected to represent “strong” and “weak” bias situations. Ensemble spread and probabilistic forecasts are compared before and after a bias correction. The results show that the conclusions drawn from ensemble verification about the EPS are dramatically different with or without model bias. This is true for both ensemble spread and probabilistic forecasts. The GRAPES-REPS is severely underdispersive before the bias correction but becomes calibrated afterward, although the improvement in the spread’s spatial structure is much less; the spread–skill relation is also improved. The probabilities become much sharper and almost perfectly reliable after the bias is removed. Therefore, it is necessary to remove forecast biases before an EPS can be accurately evaluated since an EPS deals only with random error but not systematic error. Only when an EPS has no or little forecast bias, can ensemble verification metrics reliably reveal the true quality of an EPS without removing forecast bias first. An implication is that EPS developers should not be expected to introduce methods to dramatically increase ensemble spread (either by perturbation method or statistical calibration) to achieve reliability. Instead, the preferred solution is to reduce model bias through prediction system developments and to focus on the quality of spread (not the quantity of spread). Forecast products should also be produced from the debiased but not the raw ensemble.
Co-producing “Post-normal” Climate Knowledge with Communities in Northeast Bangladesh
Authors: Bremer S. , Stiller-Reeve M. , Blanchard A. , Mamnun N. , Naznin Z. , Kaiser M.
Published: February 2018

Concepts of knowledge “co-production” are increasingly encouraged in climate research, including as an extended mode of climate science inquiry. So-called “post-normal” science offers opportunities to advance this branch of co-production research with theory and methods. However, the literature lacks material of how to “do” climate knowledge co-production as extended science, and particularly as post-normal science.

This paper presents an account of post-normal science theory and how it guided the TRACKS (Transforming Climate Knowledge with and for Society) project’s research practice, co-producing climate knowledge with communities in northeast Bangladesh. Key principles of post-normal science are described and explanations given of how they were translated into the research process, and specifically into workshops. The paper therefore provides insights for scholars and practitioners on one form of knowledge co-production, and thus contributes to this growing scholarship.