bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of Bioavailability-Based Toxicity Models for Metals
Authors: Garman Emily R. , Meyer Joseph S. , Bergeron Christine M. , Blewett Tamzin A. , Clements William H. , Elias Michael C. , Farley Kevin J. , Gissi Francesca , Ryan Adam C. 
Published: December 2019

Abstract
Regulatory jurisdictions worldwide are increasingly incorporating bioavailability-based toxicity models into development of protective values (PVALs) for freshwater and saltwater aquatic life (e.g., water quality criteria, standards, and/or guidelines) for metals. Use of such models for regulatory purposes should be contingent on their ability to meet performance criteria as specified through a model-validation process. Model validation generally involves an assessment of a model's appropriateness, relevance, and accuracy. We review existing guidance for validation of bioavailability-based toxicity models, recommend questions that should be addressed in model-validation studies, discuss model study type and design considerations, present several new ways to evaluate model performance in validation studies, and suggest a framework for use of model validation in PVAL development. We conclude that model validation should be rigorous but flexible enough to fit the user's purpose. Although a model can never be fully validated to a level of zero uncertainty, it can be sufficiently validated to fit a specific purpose. Therefore, support (or lack of support) for a model should be presented in such a way that users can choose their own level of acceptability. We recommend that models be validated using experimental designs and endpoints consistent with the data sets that were used to parameterize and calibrate the model and validated across a broad range of geographically and ecologically relevant water types. Environ Toxicol Chem 2019;39:101–117. © 2019 SETAC
Development of Empirical Bioavailability Models for Metals
Authors: Brix Kevin V. , DeForest David K. , Tear Lucinda , Peijnenburg Willie , Peters Adam , Middleton Ellie T. , Erickson Russ 
Published: December 2019

Abstract
Recently, there has been renewed interest in the development and use of empirical models to predict metal bioavailability and derive protective values for aquatic life. However, there is considerable variability in the conceptual and statistical approaches with which these models have been developed. In the present study, we review case studies of empirical bioavailability model development, evaluating and making recommendations on key issues, including species selection, identifying toxicity-modifying factors (TMFs) and the appropriate environmental range of these factors, use of existing toxicity data sets and experimental design for developing new data sets, statistical considerations in deriving species-specific and pooled bioavailability models, and normalization of species sensitivity distributions using these models. We recommend that TMFs be identified from a combination of available chemical speciation and toxicity data and statistical evaluations of their relationships to toxicity. Experimental designs for new toxicity data must be sufficiently robust to detect nonlinear responses to TMFs and should encompass a large fraction (e.g., 90%) of the TMF range. Model development should involve a rigorous use of both visual plotting and statistical techniques to evaluate data fit. When data allow, we recommend using a simple linear model structure and developing pooled models rather than retaining multiple taxa-specific models. We conclude that empirical bioavailability models often have similar predictive capabilities compared to mechanistic models and can provide a relatively simple, transparent tool for predicting the effects of TMFs on metal bioavailability to achieve desired environmental management goals. Environ Toxicol Chem 2019;39:85–100. © 2019 SETAC
An adaptive resource placement policy by optimizing live VM migration for ITS applications in vehicular cloud network
Authors: Midya Sadip , Roy Asmita , Majumder Koushik , Phadikar Santanu 
Published: December 2019

AbstractVehicular cloud computing (VCC) is a promising approach that uses cloud computing techniques in vehicular environment to execute smart applications. Vehicular environment is characterized by high mobility. This requires the services executed by a vehicular resource in a vehicular cloud to be migrated before it leaves a network. Migration is also required when a service‐requesting vehicle has to leave a network before its request is executed. Moreover, to balance the network load, virtual machine (VM) migration is desired as, at times, a single physical host may become overloaded. In this work, we propose an adaptive resource placement policy by optimizing live VM migration process in vehicular cloud network. The Pareto optimal mapping of migrating VMs to a physical host is carried out using a hybrid optimized algorithm, which is the combination of particle swarm optimization and genetic algorithm. The optimization is done by maximizing a fitness function that is developed by considering significant quality‐of‐service (QoS) parameters, such as network latency, migration delay, power consumption, and vehicular mobility. These QoS parameters are mathematically formulated in view of a vehicular network. The proposed algorithm reduces migration latency, transmission latency, and service delay. It also distributes the load among the available physical hosts within a cloud system, thus reducing the average wait time for each cloud user. Simulation results exhibit significant decrease in waiting time, service delay, and migration delay. It is also shown that the proposed algorithm reduces total power consumption of the system.
Optimal energy beamforming under per‐antenna power constraint
Authors: Rezaei Zahra , Yazdian Ehsan , Tabataba Foroogh S. , Gazor Saeed 
Published: December 2019

AbstractEnergy beamforming (EB) is a key technique to enhance the efficiency of wireless power transfer. In this paper, we study the optimal EB under per‐antenna power constraint (PAC), which is more practical than the conventional sum‐power constraint. We consider a multiantenna energy transmitter with PAC that broadcasts wireless energy to multiple energy receivers (ER)s. We consider sum‐energy maximization problem with PAC and provide the optimal solution structure for the general case. This optimal structure implies that sending one energy beam is optimal under PAC, which means that the rank of transmit covariance matrix is one similar to sum‐power constraint. We also derive closed‐form solutions for two special cases and propose two suboptimal solutions for general case, which performs very close to optimal beamforming.
Does the facilitator of a scenario development activity need substantive knowledge of the focal topic?
Authors: Wright George , Cairns George 
Published: December 2019

AbstractThis short paper focuses on the facilitation of scenario development activity using the intuitive logics method. Counter‐intuitively, substantive knowledge of the focal scenario topic is not crucial. More important is the facilitator's active, intelligent involvement with participants over the whole of the scenario development process. In scenario development within a single organization, it is useful to have an assistant from the host organization who has both substantive knowledge of the focal topic and an interest in learning about scenario thinking. Within multi‐agency interventions, important issues for the facilitator to resolve are the potentially conflicted goals of participants and the extent of the involvement of senior‐level decision makers.
Ordered multinomial regression for genetic association analysis of ordinal phenotypes at Biobank scale
Authors: German Christopher A. , Sinsheimer Janet S. , Klimentidis Yann C. , Zhou Hua , Zhou Jin J. 
Published: December 2019

AbstractLogistic regression is the primary analysis tool for binary traits in genome‐wide association studies (GWAS). Multinomial regression extends logistic regression to multiple categories. However, many phenotypes more naturally take ordered, discrete values. Examples include (a) subtypes defined from multiple sources of clinical information and (b) derived phenotypes generated by specific phenotyping algorithms for electronic health records (EHR). GWAS of ordinal traits have been problematic. Dichotomizing can lead to a range of arbitrary cutoff values, generating inconsistent, hard to interpret results. Using multinomial regression ignores trait value hierarchy and potentially loses power. Treating ordinal data as quantitative can lead to misleading inference. To address these issues, we analyze ordinal traits with an ordered, multinomial model. This approach increases power and leads to more interpretable results. We derive efficient algorithms for computing test statistics, making ordinal trait GWAS computationally practical for Biobank scale data. Our method is available as a Julia package OrdinalGWAS.jl. Application to a COPDGene study confirms previously found signals based on binary case–control status, but with more significance. Additionally, we demonstrate the capability of our package to run on UK Biobank data by analyzing hypertension as an ordinal trait.
CCS takes centre stage
Authors: Cozier Muriel 
Published: December 2019

AbstractThe words ‘high level’ and ‘carbon capture and storage’ (CCS) are beginning to crop up in the same sentence more frequently. CCS has indeed made its way into the high‐level discussions on which tools need to be deployed to mitigate climate change. In this article GHGS&T's Muriel Cozier reviews the European High Level Conference on Carbon Capture and Storage and looks to see if CCS has, at last, come of age. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Regulation of food intake by astrocytes in the brainstem dorsal vagal complex
Authors: MacDonald Alastair J. , Holmes Fiona E. , Beall Craig , Pickering Anthony E. , Ellacott Kate L. J. 
Published: December 2019

AbstractA role for glial cells in brain circuits controlling feeding has begun to be identified with hypothalamic astrocyte signaling implicated in regulating energy homeostasis. The nucleus of the solitary tract (NTS), within the brainstem dorsal vagal complex (DVC), integrates vagal afferent information from the viscera and plays a role in regulating food intake. We hypothesized that astrocytes in this nucleus respond to, and influence, food intake. Mice fed high‐fat chow for 12 hr during the dark phase showed NTS astrocyte activation, reflected in an increase in the number (65%) and morphological complexity of glial‐fibrillary acidic protein (GFAP)‐immunoreactive cells adjacent to the area postrema (AP), compared to control chow fed mice. To measure the impact of astrocyte activation on food intake, we delivered designer receptors exclusively activated by designer drugs (DREADDs) to DVC astrocytes (encompassing NTS, AP, and dorsal motor nucleus of the vagus) using an adeno‐associated viral (AAV) vector (AAV‐GFAP‐hM3Dq_mCherry). Chemogenetic activation with clozapine‐N‐oxide (0.3 mg/kg) produced in greater morphological complexity in astrocytes and reduced dark‐phase feeding by 84% at 4 hr postinjection compared with vehicle treatment. hM3Dq‐activation of DVC astrocytes also reduced refeeding after an overnight fast (71% lower, 4 hr postinjection) when compared to AAV‐GFAP‐mCherry expressing control mice. DREADD‐mediated astrocyte activation did not impact locomotion. hM3Dq activation of DVC astrocytes induced c‐FOS in neighboring neuronal feeding circuits (including in the parabrachial nucleus). This indicates that NTS astrocytes respond to acute nutritional excess, are involved in the integration of peripheral satiety signals, and can reduce food intake when activated.
Modulation of Biliary Cancer Chemo‐Resistance Through MicroRNA‐Mediated Rewiring of the Expansion of CD133+ Cells
Authors: Carotenuto Pietro , Hedayat Somaieh , Fassan Matteo , Cardinale Vincenzo , Lampis Andrea , Guzzardo Vincenza , Vicentini Caterina , Scarpa Aldo , Cascione Luciano , Costantini Daniele , Carpino Guido , Alvaro Domenico , Ghidini Michele , Trevisani Francesco , Te Poele Robert , Salati Massimiliano , Ventura Sofia , Vlachogiannis Georgios , Hahne Jens C. , Boulter Luke , Forbes Stuart J. , Guest Rachel V. , Cillo Umberto , Said‐Huntingford Ian , Begum Ruwaida , Smyth Elizabeth , Michalarea Vasiliki , Cunningham David , Rimassa Lorenza , Santoro Armando , Roncalli Massimo , Kirkin Vladimir , Clarke Paul , Workman Paul , Valeri Nicola , Braconi Chiara 
Published: December 2019

Background and Aims
Changes in single microRNA (miRNA) expression have been associated with chemo‐resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never been performed to identify potential therapeutic targets that are functionally relevant in the BTC cell response to chemotherapy.

Approach and Results
High‐throughput screening (HTS) of 997 locked nucleic acid miRNA inhibitors was performed in six cholangiocarcinoma cell lines treated with cisplatin and gemcitabine (CG) seeking changes in cell viability. Validation experiments were performed with mirVana probes. MicroRNA and gene expression was assessed by TaqMan assay, RNA‐sequencing, and in situ hybridization in four independent cohorts of human BTCs. Knockout of microRNA was achieved by CRISPR‐CAS9 in CCLP cells (MIR1249KO) and tested for effects on chemotherapy sensitivity in vitro and in vivo. HTS revealed that MIR1249 inhibition enhanced chemotherapy sensitivity across all cell lines. MIR1249 expression was increased in 41% of cases in human BTCs. In validation experiments, MIR1249 inhibition did not alter cell viability in untreated or dimethyl sulfoxide–treated cells; however, it did increase the CG effect. MIR1249 expression was increased in CD133+ biliary cancer cells freshly isolated from the stem cell niche of human BTCs as well as in CD133+ chemo‐resistant CCLP cells. MIR1249 modulated the chemotherapy‐induced enrichment of CD133+ cells by controlling their clonal expansion through the Wnt‐regulator FZD8. MIR1249KO cells had impaired expansion of the CD133+ subclone and its enrichment after chemotherapy, reduced expression of cancer stem cell markers, and increased chemosensitivity. MIR1249KO xenograft BTC models showed tumor shrinkage after exposure to weekly CG, whereas wild‐type models showed only stable disease over treatment.

Conclusions
MIR1249 mediates resistance to CG in BTCs and may be tested as a target for therapeutics.
Investigation of multiphasic 3D‐bioplotted scaffolds for site‐specific chondrogenic and osteogenic differentiation of human adipose‐derived stem cells for osteochondral tissue engineering applications
Authors: Mellor Liliana F. , Nordberg Rachel C. , Huebner Pedro , Mohiti‐Asli Mahsa , Taylor Michael A. , Efird William , Oxford Julia T. , Spang Jeffrey T. , Shirwaiker Rohan A. , Loboa Elizabeth G. 
Published: December 2019

AbstractOsteoarthritis is a degenerative joint disease that limits mobility of the affected joint due to the degradation of articular cartilage and subchondral bone. The limited regenerative capacity of cartilage presents significant challenges when attempting to repair or reverse the effects of cartilage degradation. Tissue engineered medical products are a promising alternative to treat osteochondral degeneration due to their potential to integrate into the patient's existing tissue. The goal of this study was to create a scaffold that would induce site‐specific osteogenic and chondrogenic differentiation of human adipose‐derived stem cells (hASC) to generate a full osteochondral implant. Scaffolds were fabricated using 3D‐bioplotting of biodegradable polycraprolactone (PCL) with either β‐tricalcium phosphate (TCP) or decellularized bovine cartilage extracellular matrix (dECM) to drive site‐specific hASC osteogenesis and chondrogenesis, respectively. PCL‐dECM scaffolds demonstrated elevated matrix deposition and organization in scaffolds seeded with hASC as well as a reduction in collagen I gene expression. 3D‐bioplotted PCL scaffolds with 20% TCP demonstrated elevated calcium deposition, endogenous alkaline phosphatase activity, and osteopontin gene expression. Osteochondral scaffolds comprised of hASC‐seeded 3D‐bioplotted PCL‐TCP, electrospun PCL, and 3D‐bioplotted PCL‐dECM phases were evaluated and demonstrated site‐specific osteochondral tissue characteristics. This technique holds great promise as cartilage morbidity is minimized since autologous cartilage harvest is not required, tissue rejection is minimized via use of an abundant and accessible source of autologous stem cells, and biofabrication techniques allow for a precise, customizable methodology to rapidly produce the scaffold.
Rac1 Inhibition Via Srgap2 Restrains Inflammatory Osteoclastogenesis and Limits the Clastokine, SLIT3
Authors: Shin Bongjin , Kupferman Justine , Schmidt Ewoud , Polleux Franck , Delany Anne M , Lee Sun-Kyeong 
Published: December 2019

ABSTRACTThe Rac1-specific guanosine triphosphatase (GTPase)-activating protein Slit-Robo GAP2 (Srgap2) is dramatically upregulated during RANKL-induced osteoclastogenesis. Srgap2 interacts with the cell membrane to locally inhibit activity of Rac1. In this study, we determined the role of Srgap2 in the myeloid lineage on bone homeostasis and the osteoclastic response to TNFα treatment. The bone phenotype of mice specifically lacking Srgap2 in the myeloid lineage (Srgap2 f/f:LysM-Cre; Srgap2 conditional knockout [cKO]) was investigated using histomorphometric analysis, in vitro cultures and Western blot analysis. Similar methods were used to determine the impact of TNFα challenge on osteoclast formation in Srgap2 cKO mice. Bone parameters in male Srgap2 cKO mice were unaffected. However, female cKO mice displayed higher trabecular bone volume due to increased osteoblast surface and bone formation rate, whereas osteoclastic parameters were unaltered. In vitro, cells from Srgap2 cKO had strongly enhanced Rac1 activation, but RANKL-induced osteoclast formation was unaffected. In contrast, conditioned medium from Srgap2 cKO osteoclasts promoted osteoblast differentiation and had increased levels of the bone anabolic clastokine SLIT3, providing a possible mechanism for increased bone formation in vivo. Rac1 is rapidly activated by the inflammatory cytokine TNFα. Supracalvarial injection of TNFα caused an augmented osteoclastic response in Srgap2 cKO mice. In vitro, cells from Srgap2 cKO mice displayed increased osteoclast formation in response to TNFα. We conclude that Srgap2 plays a prominent role in limiting osteoclastogenesis during inflammation through Rac1, and restricts expression of the paracrine clastokine SLIT3, a positive regulator of bone formation. © 2019 American Society for Bone and Mineral Research.
Association of polymorphisms in MALAT1 with the risk of endometrial cancer in Southern Chinese women
Authors: Chen Guange , Zhang Mingyao , Liang Zongwen , Chen Sailing , Chen Feng , Zhu Jiawei , Zhao Manman , He Jing , Hua Wenfeng , Duan Ping 
Published: December 2019

AbstractBackgroundEndometrial cancer is the most common gynecologic malignancy worldwide. Polymorphisms in MALAT1 have been demonstrated to play critical roles in cancer. However, the roles of MALAT1 polymorphisms in the etiology of endometrial cancer have not been well documented.MethodsWe genotyped three MALAT1 polymorphisms in 249 endometrial cancer cases and 446 cancer‐free female controls using quantitative polymerase chain reaction with TaqMan probes. To estimate the association between MALAT1 polymorphisms (rs591291 C>T, rs664589 C>G, and rs4102217 G>C) and the risk of endometrial cancer, an unconditional logistic regression model was conducted to calculate the odds ratio (OR) and the 95% confidence interval (CI), adjusting for surgery history, menopause, number of deliveries, BMI, and FIGO stage.ResultsWe found that the MALAT1 rs664589 C>G polymorphism was significantly associated with endometrial cancer risk (heterogeneous: adjusted OR = 0.57, 95% CI = 0.34‐0.93, P = .026; homogenous: adjusted OR = 3.74, 95% CI = 1.12‐12.45, P = .032; and recessive: adjusted OR = 4.06, 95% CI = 1.22‐13.48, P = .022). Stratified analysis further demonstrated that the MALAT1 rs664589 C>G polymorphism significantly increased the risk of endometrial cancer susceptibility in patients with no history of surgery, more deliveries, BMI between 25 and 29.9, and FIGO stages II‐III. Compared with the wild‐type GCG haplotype carriers, individuals with CGG haplotypes had a higher risk of developing endometrial cancer.ConclusionThe MALAT1 rs664589 C>G polymorphism was associated with a significant increase in endometrial cancer risk.
Predictive value of long non‐coding RNA intersectin 1‐2 for occurrence and in‐hospital mortality of severe acute pancreatitis
Authors: Li Jun , Bu Xiaofen , Chen Xuanlan , Xiong Peng , Chen Zhen , Yu Li 
Published: December 2019

AbstractBackgroundThis study aimed to investigate the predictive value of long non‐coding RNA intersectin 1‐2 (lnc‐ITSN1‐2) for severe acute pancreatitis (SAP) risk, and its correlation with disease severity and in‐hospital mortality in SAP patients.MethodsPlasma samples from 60 SAP, 60 moderate‐severe acute pancreatitis (MSAP) and 60 mild acute pancreatitis (MAP) patients were collected within 24 hours, and plasma samples from 60 age and gender‐matched healthy controls (HCs) were collected when enrollment. Lnc‐ITSN1‐2 was detected by reverse transcription‐quantitative polymerase chain reaction. In AP patients, disease severity was evaluated and in‐hospital deaths were recorded.ResultsLnc‐ITSN1‐2 was increased in SAP patients compared with MSAP, MAP patients, and HCs, and it is well‐discriminated SAP patients from MSAP patients (area under curve (AUC): 0.699, 95% confidence interval (CI): 0.605‐0.792), MAP patients (AUC: 0.862, 95% CI: 0.798‐0.926), and HCs (AUC: 0.958, 95% CI: 0.925‐0.990). For disease severity, lnc‐ITSN1‐2 was positively correlated with Ranson's score, acute pathologic and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and C‐reactive protein (CRP) in SAP patients, MSAP patients, and MAP patients; meanwhile, the correlation coefficients were highest in SAP patients. Furthermore, lnc‐ITSN1‐2 displayed a good predictive value for increased in‐hospital mortality in SAP (AUC: 0.803, 95% CI: 0.673‐0.933) and MSAP (AUC: 0.854, 95% CI: 0.752‐0.956) patients, which was similar with several common prognostic factors (including Ranson's score, APACHE II score, SOFA score, and CRP).ConclusionLnc‐ITSN1‐2 might be a potential biomarker for discrimination of SAP to improve the prognosis of SAP patients.
miR‐647 inhibits glioma cell proliferation, colony formation and invasion by regulating HOXA9
Authors: Qin Kun , Tian Ge , Chen Guangzhong , Zhou Dong , Tang Kai 
Published: December 2019

AbstractBackgroundMicroRNA‐647 (miR‐647) has been reported to regulate tumor development, although its role in glioma remains unclear.MethodsmiR‐647 expression in glioma cells and normal cells was measured using a quantitative real‐time polymerase chain reaction. The effects of miR‐647 expression on glioma cell proliferation, cell apoptosis, colony formation and cell invasion were measured using a cell counting kit‐8 assay, flow cytometry, a colony formation assay and a transwell invasion assay. Luciferase activity reporter and western blot assays were conducted to explore whether homeobox A9 (HOXA9) was a direct target of miR‐647.ResultsWe found that miR‐647 expression was downregulated in glioma cell lines compared to the normal cell line. Overexpression of miR‐647 inhibits glioma cell proliferation, colony formation and cell invasion, although it promotes apoptosis in vitro. HOXA9 was validated a direct target of miR‐647 and the overexpression of HOXA9 reversed the effects of miR‐647 on glioma cell behavior.ConclusionsThe identification of the miR‐647/HOXA9 axis will advance our understanding underlying glioma progression and provide novel therapeutic targets for glioma treatment.