bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression analysis and in vitro production procedures for bovine preimplantation embryos: Past highlights, present concepts and future prospects
Authors: Wrenzycki Christine 
Published: September 2018

ContentsOver the past decades in vitro production (IVP) of bovine embryos has been significantly improved and in particular bovine IVP is now widely applied under field conditions. This in vitro technique provides new opportunities for cattle producers, particularly in the dairy industry, to overcome infertility and to increase dissemination of animals with high genetic merit. Improvements in OPU/IVP resulted in large‐scale international commercialization. More than half a million IVP embryos are generated on the yearly basis demonstrating the enormous potential of this technology. These advances and the fact that bovine and human early development is remarkably similar have also prompted the use of bovine embryos as a model system to study early mammalian embryogenesis including humans. Despite all the improvements, embryos generated in vitro still differ from their in vivo derived counterparts. Embryos must adjust to multiple microenvironments at preimplantation stages. Consequently, maintaining or mimicking the in vivo situation in vitro will aid to improve the quality and developmental competence of the resulting embryo. The successful clinical application of the techniques in reproductive biotechnology requires both species‐specific clinical skills and extensive laboratory experience. The recent advances in transcriptome profiling have also provided deeper insight into RNA expression and regulation at an unprecedented resolution. The development of these high‐throughput DNA sequencing methods has resulted in new approaches for both mapping and quantifying transcriptomes. The aim of this review is therefore to summarize the available data related to gene expression analyses as well as in vitro embryo production procedures and to provide ideas about future concepts.
Risk‐based decision making in transfusion medicine
Authors: Leach Bennett Judie , Devine Dana V. 
Published: September 2018

AbstractFormal processes to assess risk are well established in numerous areas of society including the environment, transportation, energy and food production sectors as well as some areas of health care such as new drugs or other therapeutic goods. However, these processes and their associated frameworks have only recently come to be used to make decisions in blood transfusion practice or in blood system policy development. This review describes the evolution of the use of risk‐based decision making and discusses the elements that should be considered in its application to blood system issues. Following the identification and characterization of the risk, a structured process is undertaken to assess the magnitude of the risk and the level of risk reduction that can reasonably be achieved in the context of the complexity of the risk management action proposed and its cost. Inputs must be sought from appropriate subject matter experts, but also from those who can consider issues of ethics and social values. Engagement of the public is an essential step. Proposed interventions should be assessed for their likelihood of mitigating the risk and the proportional resource allocation in comparison with similar risks to the blood system or health system. Examples are provided of how a risk‐based decision‐making framework is used to address identified risks in the blood system.
Association between bronchopulmonary dysplasia and cerebral palsy in children: a meta-analysis
Authors: Gou Xiaoyun , Yang Lei , Pan Lingli , Xiao Dongqiong 
Published: September 2018

ObjectiveTo investigate the association between bronchopulmonary dysplasia (BPD) and the risk of cerebral palsy (CP) in children.Data sourcesWe used EMBASE, PubMed and Web of Science to conduct a meta-analysis of studies published before 1 September 2017, written in English whose titles or abstracts discussed an association between BPD and CP.Study selectionObservational studies, for example, case–control and cohort studies were included.Data extraction and synthesisAll review stages were conducted by two reviewers independently. Data synthesis was undertaken via meta-analysis of available evidence.Main outcomes and measuresThe prevalence of developing CP was measured after exposure to BPD.ResultsAmong 1234 initially identified studies, we selected those that addressed an association between BPD and CP according to our preselected inclusion criteria. Our meta-analysis included 11 studies. According to a random effect model, BPD was significantly associated with CP (ORs 2.10; 95% CI 1.57 to 2.82) in preterm infants. Factors explaining differences in the study results included study design, the definition of BPD, the time of diagnosis of CP and whether the studies adjusted for potential confounders.ConclusionThis study suggests that BPD is a risk factor for CP. Further studies are required to confirm these results and to detect the influence of variables across studies.
Classic e-Delphi survey to provide national consensus and establish priorities with regards to the factors that promote the implementation and continued development of non-medical prescribing within health services in Wales
Authors: Courtenay Molly , Deslandes Rhian , Harries-Huntley Gail , Hodson Karen , Morris Gary 
Published: September 2018

ObjectiveTo provide national consensus and establish priorities with regards to the factors that promote the implementation and continued development of non-medical prescribing within health services.DesignClassic e-Delphi survey.SettingNational study in Wales.ParticipantsPharmacists, nurses and allied health professionals with the independent/supplementary prescribing qualification.ResultsA total of 55 non-medical prescribers agreed to become members of the expert panel of whom 42 (76%) completed the round 1 questionnaire, 40/42 (95%) completed round 2 and 34/40 (85%) responded to round 3. Twenty-one statements were developed, and consensus was achieved on nine factors representing those necessary for the successful implementation of non-medical prescribing and five representing actions required for its continued development. Strategic fit between non-medical prescribing and existing service provision, organisation preparedness, visible benefits, good managerial and team support, and a clear differentiation of roles were each important influences.ConclusionGiven the high degree of consensus, this list of factors and actions should provide guidance to managers and commissioners of services wishing to initiate or extend non-medical prescribing. This information should be considered internationally by other countries outside of the UK wishing to implement prescribing by non-medical healthcare professionals.
Assessing the long-term effectiveness of interferon-beta and glatiramer acetate in multiple sclerosis: final 10-year results from the UK multiple sclerosis risk-sharing scheme
Authors: Palace Jacqueline , Duddy Martin , Lawton Michael , Bregenzer Thomas , Zhu Feng , Boggild Mike , Piske Benjamin , Robertson Neil P , Oger Joel , Tremlett Helen , Tilling Kate , Ben-Shlomo Yoav , Lilford Richard , Dobson Charles 
Published: September 2018

BackgroundBecause multiple sclerosis (MS) is a chronic disease causing disability over decades, it is crucial to know if the short-term effects of disease-modifying therapies reported in randomised controlled trials reduce long-term disability. This 10-year prospective observational study of disability outcomes (Expanded Disability Status Scale (EDSS) and utility) was set up, in conjunction with a risk-sharing agreement between payers and producers, to investigate this issue.MethodsThe outcomes of the UK treated patients were compared with a modelled untreated control based on the British Columbia MS data set to assess the long-term effectiveness of these treatments. Two complementary analysis models were used: a multilevel model (MLM) and a continuous Markov model.Results4862 patients with MS were eligible for the primary analysis (mean and median follow-up times 8.7 and 10 years). EDSS worsening was reduced by 28% (MLM), 7% (Markov) and 24% time-adjusted Markov in the total cohort, and by 31% (MLM) and 14% (Markov) for relapsing remitting patients. The utility worsening was reduced by 23%–24% in the total cohort and by 24%–31% in the RR patients depending on the model used. All sensitivity analyses showed a treatment effect. There was a 4-year (CI 2.7 to 5.3) delay to EDSS 6.0. An apparent waning of treatment effect with time was seen. Subgroup analyses suggested better treatment effects in those treated earlier and with lower EDSS scores.ConclusionsThis study supports a beneficial effect on long-term disability with first-line MS disease-modifying treatments, which is clinically meaningful. However the waning effect noted requires further study.
Measuring low-altitude wind gusts using the unmanned aerial vehicle GustAV
Authors: Yeung Alton , Bramesfeld Goetz , Chung Joon , Foster Stephen 
Published: September 2018

A small unmanned aerial vehicle (SUAV) was developed with the specific objective to explore atmospheric wind gusts at low altitudes below 500 m. These gusts have significant impact on the flight characteristics and performance of SUAVs. The SUAV carried an advanced air-data system that includes a five-hole probe, which was adapted for this specific application. In several flight tests the entire test system was qualified and gust data were recorded. The subsequent experimentally derived gust data were post-processed and compared with turbulence spectra of the MIL-HDBK-1797 von Kármán turbulence model. On the day of the flight test, the experimental results did not fully match the prediction of the von Kármán model. Meanwhile, the wind measuring apparatus were proven to be able to measure gust during flight. Therefore, a broader sampling will be required to generalize the gust measurements and be compared with the existing models.
Androgen Receptor Inhibitor Enhances the Antitumor Effect of PARP Inhibitor in Breast Cancer Cells by Modulating DNA Damage Response
Authors: Min Ahrum , Jang Hyemin , Kim Seongyeong , Lee Kyung-Hun , Kim Debora Keunyoung , Suh Koung Jin , Yang Yaewon , Elvin Paul , O'Connor Mark J. , Im Seock-Ah 
Published: September 2018

Abstract
The androgen receptor (AR) is expressed in 60%–70% of breast cancers regardless of estrogen receptor status, and has been proposed as a therapeutic target in breast cancers that retain AR. In this study, the authors aimed to investigate a new treatment strategy using a novel AR inhibitor AZD3514 in breast cancer. AZD3514 alone had a minimal antiproliferative effect on most breast cancer cell lines irrespective of AR expression level, but it downregulated the expressions of DNA damage response (DDR) molecules, including ATM and chk2, which resulted in the accumulation of damaged DNA in some breast cancer cells. Furthermore, AZD3514 enhanced cellular sensitivity to a PARP inhibitor olaparib by blocking the DDR pathway in breast cancer cells. Furthermore, the downregulation of NKX3.1 expression in MDA-MB-468 cells by AZD3514 occurred in parallel with the suppression of ATM–chk2 axis activation, and the suppression of NKX3.1 by AZD3514 was found to result from AZD3514-induced TOPORS upregulation and a resultant increase in NKX3.1 degradation. The study shows posttranslational regulation of NKX3.1 via TOPORS upregulation by AZD3514-induced ATM inactivation–increased olaparib sensitivity in AR-positive and TOPORS-expressing breast cancer cells, and suggests the antitumor effect of AZD3514/olaparib cotreatment is caused by compromised DDR activity in breast cancer cell lines and in a xenograft model. These results provide a rationale for future clinical trials of olaparib/AR inhibitor combination treatment in breast cancer.
Histone Deacetylase Inhibitors Synergize with Catalytic Inhibitors of EZH2 to Exhibit Antitumor Activity in Small Cell Carcinoma of the Ovary, Hypercalcemic Type
Authors: Wang Yemin , Chen Shary Yuting , Colborne Shane , Lambert Galen , Shin Chae Young , Santos Nancy Dos , Orlando Krystal A. , Lang Jessica D. , Hendricks William P.D. , Bally Marcel B. , Karnezis Anthony N. , Hass Ralf , Underhill T. Michael , Morin Gregg B. , Trent Jeffrey M. , Weissman Bernard E. , Huntsman David G. 
Published: September 2018

Abstract
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but extremely lethal malignancy that mainly impacts young women. SCCOHT is characterized by a diploid genome with loss of SMARCA4 and lack of SMARCA2 expression, two mutually exclusive ATPases of the SWI/SNF chromatin-remodeling complex. We and others have identified the histone methyltransferase EZH2 as a promising therapeutic target for SCCOHT, suggesting that SCCOHT cells depend on the alternation of epigenetic pathways for survival. In this study, we found that SCCOHT cells were more sensitive to pan-HDAC inhibitors compared with other ovarian cancer lines or immortalized cell lines tested. Pan-HDAC inhibitors, such as quisinostat, reversed the expression of a group of proteins that were deregulated in SCCOHT cells due to SMARCA4 loss, leading to growth arrest, apoptosis, and differentiation in vitro and suppressed tumor growth of xenografted tumors of SCCOHT cells. Moreover, combined treatment of HDAC inhibitors and EZH2 inhibitors at sublethal doses synergistically induced histone H3K27 acetylation and target gene expression, leading to rapid induction of apoptosis and growth suppression of SCCOHT cells and xenografted tumors. Therefore, our preclinical study highlighted the therapeutic potential of combined treatment of HDAC inhibitors with EZH2 catalytic inhibitors to treat SCCOHT.
Targeted Delivery of Cytotoxic NAMPT Inhibitors Using Antibody–Drug Conjugates
Authors: Neumann Christopher S. , Olivas Kathleen C. , Anderson Martha E. , Cochran Julia H. , Jin Steven , Li Fu , Loftus Luke V. , Meyer David W. , Neale Jason , Nix Jay C. , Pittman Paul G. , Simmons Jessica K. , Ulrich Michelle L. , Waight Andrew B. , Wong Abbie , Zaval Margo C. , Zeng Weiping , Lyon Robert P. , Senter Peter D. 
Published: September 2018

Abstract
Antibody–drug conjugates (ADCs) are a therapeutic modality that enables the targeted delivery of cytotoxic drugs to cancer cells. Identification of active payloads with unique mechanisms of action is a key aim of research efforts in the field. Herein, we report the development of inhibitors of nicotinamide phosphoribosyltransferase (NAMPT) as a novel payload for ADC technology. NAMPT is a component of a salvage biosynthetic pathway for NAD, and inhibition of this enzyme results in disruption of primary cellular metabolism leading to cell death. Through derivatization of the prototypical NAMPT inhibitor FK-866, we identified potent analogues with chemical functionality that enables the synthesis of hydrophilic enzyme-cleavable drug linkers. The resulting ADCs displayed NAD depletion in both cell-based assays and tumor xenografts. Antitumor efficacy is demonstrated in five mouse xenograft models using ADCs directed to indication-specific antigens. In rat toxicology models, a nonbinding control ADC was tolerated at &gt;10-fold the typical efficacious dose used in xenografts. Moderate, reversible hematologic effects were observed with ADCs in rats, but there was no evidence for the retinal and cardiac toxicities reported for small-molecule inhibitors. These findings introduce NAMPT inhibitors as active and well-tolerated payloads for ADCs with promise to improve the therapeutic window of NAMPT inhibition and enable application in clinical settings.
Targeting TAZ-Driven Human Breast Cancer by Inhibiting a SKP2-p27 Signaling Axis
Authors: Shen He , Yang Nuo , Truskinovsky Alexander , Chen Yanmin , Mussell Ashley L. , Nowak Norma J. , Kobzik Lester , Frangou Costa , Zhang Jianmin 
Published: September 2018

Abstract

Deregulated expression of the transcriptional coactivator with PDZ-binding motif (WWTR1/TAZ) is a common feature of basal-like breast cancer (BLBC). Yet, how oncogenic TAZ regulates cell-cycle progression and proliferation in breast cancer remains poorly understood, and whether TAZ is required for tumor maintenance has not been established. Here, using an integrative oncogenomic approach, TAZ-dependent cellular programs essential for tumor growth and progression were identified. Significantly, TAZ-driven tumor cells required sustained TAZ expression, given that its withdrawal impaired both genesis and maintenance of solid tumors. Moreover, temporal inhibition of TAZ diminished the metastatic burden in established macroscopic pulmonary metastases. Mechanistic investigation revealed that TAZ controls distinct gene profiles that determine cancer cell fate through cell-cycle networks, including a specific, causal role for S-phase kinase–associated protein 2 (SKP2) in mediating the neoplastic state. Together, this study elucidates the molecular events that underpin the role of TAZ in BLBC and link to SKP2, a convergent communication node for multiple cancer signaling pathways, as a key downstream effector molecule.

Implications:
Understanding the molecular role of TAZ and its link to SKP2, a signaling convergent point and key regulator in BLBC, represents an important step toward the identification of novel therapeutic targets for TAZ-dependent breast cancer.
Hutcheson sobre a importância de ser desinteressado. Um encômio a Shaftesbury?
Authors: Jaffro Laurent 
Published: September 2018

Costuma-se dizer que a filososfia moral de Hutcheson seria tributária daquela de Shaftesbury, a ponto mesmo de ser um prolongamento do pensamento moral do filósofo inglês. O artigo busca mostrar que essa é uma visão simplista, examinando para tanto o conceito de desinteresse em Hutcheson.
Holy Strangers
Authors: Formenti Ambra 
Published: September 2018

Abstract
This article explores the religious lives of migrants in the African diaspora by focusing on the case of the Missão Evangélica Lusófona (MEL), a congregation settled on the outskirts of Lisbon and formed by migrants from Guinea-Bissau and other Portuguese-speaking countries. MEL is portrayed as an example of how Christian faith enables African believers to cross transnational spaces and to create new spiritual placements in the local environment they inhabit. Against the background of postcolonial Portugal, MEL’s mission discourses are analysed as narratives of moral empowerment that invert the stigmatizing representations of African migrants expressed by their Portuguese-born neighbours. Through these narratives, it is suggested, Evangelical Guinean migrants are able to face their historical and social condition of marginality, by developing a spiritual citizenship grounded in the idea of a Lusophone space of mission.
Leisure in Aristotle’s Political Thought
Authors: Snyder Jacob T. 
Published: September 2018

Abstract
The concept of leisure found in Aristotle’s corpus is both elusive and challenging. It eludes categorization into our current understandings of work and play while at the same time challenging those very conceptions. Here, I attempt to come to grips with Aristotelian leisure by (1) demonstrating its centrality in Aristotle’s thought, (2) explaining leisure as primarily a ‘way of being’ rather than merely the absence of occupation or one of several preconditions to the virtues, and (3) exploring what leisure might mean to liberal democracy. As a ‘way of being’, Aristotelian leisure is more than an absence of work, but is a positive comportment that itself requires virtues, material means, and an education.
On the Role of Entrainment in the Fate of Cumulus Thermals
Authors: Hernandez-Deckers Daniel , Sherwood Steven C. 
Published: September 2018

Abstract
Mixing is one of the most important processes associated with atmospheric moist convection. It determines the two-way interaction between clouds and their environment, thus having a direct impact on the time evolution of convection. The fractional entrainment rate ε—the main parameter related to mixing—is often parameterized in global circulation models as a function of updraft properties, and at the same time has a strong influence on how convection evolves. Within the framework of cumulus thermal vortices in large-eddy simulations of convection, here we first investigate the validity of some of the most common parameterizations of ε, and then investigate how relevant ε is for the fate of these thermals. We find that 1/R, where R is a measure of the thermal’s radius, best parameterizes ε, but it explains only about 20% of the total variance. On the other hand, we find that both ε and favorable initial conditions—including high initial saturated fraction of the thermals—are key factors that affect the thermals’ ascent rate, mean buoyancy, and distance traveled. The lifetimes of thermals, however, seem not to be affected significantly by either ε or initial conditions, which supports the view of cumulus convection as a succession of many short-lived thermals. Finally, our results suggest that for the majority of in-cloud cumulus thermals the important role of environmental moisture in the deepening of convection results mainly from providing the initial moisture for the short-lived thermals as they initiate at different altitudes above cloud base, rather than favoring their buoyancy as they rise through it.
The Global Historical Climatology Network Monthly Temperature Dataset, Version 4
Authors: Menne Matthew J. , Williams Claude N. , Gleason Byron E. , Rennie J. Jared , Lawrimore Jay H. 
Published: September 2018

AbstractWe describe a fourth version of the Global Historical Climatology Network (GHCN)-monthly (GHCNm) temperature dataset. Version 4 (v4) fulfills the goal of aligning GHCNm temperature values with the GHCN-daily dataset and makes use of data from previous versions of GHCNm as well as data collated under the auspices of the International Surface Temperature Initiative. GHCNm v4 has many thousands of additional stations compared to version 3 (v3) both historically and with short time-delay updates. The greater number of stations as well as the use of records with incomplete data during the base period provides for greater global coverage throughout the record compared to earlier versions. Like v3, the monthly averages are screened for random errors and homogenized to address systematic errors. New to v4, uncertainties are calculated for each station series, and regional uncertainties scale directly from the station uncertainties. Correlated errors in the station series are quantified by running the homogenization algorithm as an ensemble. Additional uncertainties associated with incomplete homogenization and use of anomalies are then incorporated into the station ensemble. Further uncertainties are quantified at the regional level, the most important of which is for incomplete spatial coverage. Overall, homogenization has a smaller impact on the v4 global trend compared to v3, though adjustments lead to much greater consistency than between the unadjusted versions. The adjusted v3 global mean therefore falls within the range of uncertainty for v4 adjusted data. Likewise, annual anomaly uncertainties for the other major independent land surface air temperature datasets overlap with GHCNm v4 uncertainties.