bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forced Activation of Notch in Macrophages Represses Tumor Growth by Upregulating miR-125a and Disabling Tumor-Associated Macrophages
Authors: Zhao Jun-Long , Huang Fei , He Fei , Gao Chun-Chen , Liang Shi-Qian , Ma Peng-Fei , Dong Guang-Ying , Han Hua , Qin Hong-Yan 
Published: January 2016

AbstractTumor-associated macrophages (TAM) contribute greatly to hallmarks of cancer. Notch blockade was shown to arrest TAM differentiation, but the precise role and underlying mechanisms require elucidation. In this study, we employed a transgenic mouse model in which the Notch1 intracellular domain (NIC) is activated conditionally to define the effects of active Notch1 signaling in macrophages. NIC overexpression had no effect on TAM differentiation, but it abrogated TAM function, leading to repressed growth of transplanted tumors. Macrophage miRNA profiling identified a novel downstream mediator of Notch signaling, miR-125a, which was upregulated through an RBP-J–binding site at the first intronic enhancer of the host gene Spaca6A. miR-125a functioned downstream of Notch signaling to reciprocally influence polarization of M1 and M2 macrophages by regulating factor inhibiting hypoxia inducible factor-1α and IRF4, respectively. Notably, macrophages transfected with miR-125a mimetics increased phagocytic activity and repressed tumor growth by remodeling the immune microenvironment. We also identified a positive feedback loop for miR-125a expression mediated by RYBP and YY1. Taken together, our results showed that Notch signaling not only supported the differentiation of TAM but also antagonized their protumorigenic function through miR-125a. Targeting this miRNA may reprogram macrophages in the tumor microenvironment and restore their antitumor potential. Cancer Res; 76(6); 1403–15. ©2016 AACR.
MACC1 Induces Tumor Progression in Transgenic Mice and Colorectal Cancer Patients via Increased Pluripotency Markers Nanog and Oct4
Authors: Lemos Clara , Hardt Markus S. , Juneja Manisha , Voss Cynthia , Förster Susann , Jerchow Boris , Haider Wolfram , Bläker Hendrik , Stein Ulrike 
Published: January 2016

Abstract
Purpose: We have previously identified the gene MACC1 as a strong prognostic biomarker for colorectal cancer metastasis and patient survival. Here, we report for the first time the generation of transgenic mouse models for MACC1.
Experimental Design: We generated mice with transgenic overexpression of MACC1 in the intestine driven by the villin promoter (vil-MACC1) and crossed them with ApcMin mice (vil-MACC1/ApcMin).
Results: vil-MACC1/ApcMin mice significantly increased the total number of tumors (P = 0.0056). This was particularly apparent in large tumors (≥3-mm diameter; P = 0.0024). A detailed histopathologic analysis of these lesions demonstrated that the tumors from the vil-MACC1/ApcMin mice had a more invasive phenotype and, consequently, showed a significantly reduced survival time than ApcMin mice (P = 0.03). Molecular analysis revealed an increased Wnt and pluripotency signaling in the tumors of vil-MACC1/ApcMin mice. Specifically, we observed a prominent upregulation of the pluripotency markers Oct4 and Nanog in these tumors compared with ApcMin controls. Finally, we could also validate that Oct4 and Nanog are regulated by MACC1 in vitro and strongly correlate with MACC1 levels in a cohort of 60 tumors of colorectal cancer patients (r = 0.7005 and r = 0.6808, respectively; P &gt; 0.0001 and P &gt; 0.0002, respectively).
Conclusions: We provide proof of principle that MACC1-induced tumor progression in colorectal cancer acts, at least in part, via the newly discovered MACC1/Nanog/Oct4 axis. These findings might have important implications for the design of novel therapeutic intervention strategies to restrict tumor progression. Clin Cancer Res; 22(11); 2812–24. ©2016 AACR.
Focusing on Core Patient-Reported Outcomes in Cancer Clinical Trials: Symptomatic Adverse Events, Physical Function, and Disease-Related Symptoms
Authors: Kluetz Paul G. , Slagle Ashley , Papadopoulos Elektra J. , Johnson Laura Lee , Donoghue Martha , Kwitkowski Virginia E. , Chen Wen-Hung , Sridhara Rajeshwari , Farrell Ann T. , Keegan Patricia , Kim Geoffrey , Pazdur Richard 
Published: January 2016

Abstract
Cancer clinical trials have relied on overall survival and measures of tumor growth or reduction to assess the efficacy of a drug. However, benefits are often accompanied by significant symptomatic toxicities. The degree to which a therapy improves disease symptoms and introduces symptomatic toxicity affects how patients function in their daily lives. These concepts are important contributors to health-related quality of life (HRQOL). In this article, we discuss patient-reported outcome (PRO) assessment in cancer trials and challenges relying solely on static multi-item HRQOL instruments. We propose focusing on three separate measures of well-defined concepts: symptomatic adverse events, physical function, and disease-related symptoms, which are key contributors to the effect of a therapy on HRQOL. Separate measures of these three concepts may facilitate the incorporation of emerging contemporary instruments that can tailor the PRO assessment strategy to different trial contexts. Irrespective of the PRO measures used, continued improvement in trial design and conduct is crucial to decrease missing data and optimize the quality of PRO information. International stakeholder collaboration and continued research into optimal practices for PRO and other clinical outcome assessments are necessary to advance a common framework for generating and reporting rigorous patient-centered data from cancer clinical trials. Clin Cancer Res; 22(7); 1553–8. ©2016 AACR.
A Prospective Study of Ripple Mapping in Atrial Tachycardias
Authors: Luther Vishal , Linton Nick W.F. , Koa-Wing Michael , Lim Phang Boon , Jamil-Copley Shahnaz , Qureshi Norman , Ng Fu Siong , Hayat Sajad , Whinnett Zachary , Davies D. Wyn , Peters Nicholas S. , Kanagaratnam Prapa 
Published: January 2016

Background—
Post ablation atrial tachycardias are characterized by low-voltage signals that challenge current mapping methods. Ripple mapping (RM) displays every electrogram deflection as a bar moving from the cardiac surface, resulting in the impression of propagating wavefronts when a series of bars move consecutively. RM displays fractionated signals in their entirety thereby helping to identify propagating activation in low-voltage areas from nonconducting tissue. We prospectively used RM to study tachycardia activation in the previously ablated left atrium.

Methods and Results—
Patients referred for atrial tachycardia ablation underwent dense electroanatomic point collection using CARTO3v4. RM was played over a bipolar voltage map and used to determine the voltage “activation threshold” that differentiated functional low voltage from nonconducting areas for each map. Ablation was guided by RM, but operators could perform entrainment or review the isochronal activation map for diagnostic uncertainty. Twenty patients were studied. Median RM determined activation threshold was 0.3 mV (0.19–0.33), with nonconducting tissue covering 33±9% of the mapped surface. All tachycardias crossed an isthmus (median, 0.52 mV, 13 mm) bordered by nonconducting tissue (70%) or had a breakout source (median, 0.35 mV) moving away from nonconducting tissue (30%). In reentrant circuits (14/20) the path length was measured (87–202 mm), with 9 of 14 also supporting a bystander circuit (path lengths, 147–234 mm). In breakout tachycardias, splitting of wavefronts resulted in 2 to 4 incomplete circuits. RM-guided ablation interrupted the tachycardia in 19 of 20 cases with the first ablation set.

Conclusions—
RM helps to define activation through low-voltage regions and aids ablation of atrial tachycardias.
Quantifying the 3 Biases That Lead to Unintentional Overestimation of the Blood Pressure–Lowering Effect of Renal Denervation
Authors: Howard James P. , Shun-Shin Matthew J. , Hartley Adam , Bhatt Deepak L. , Krum Henry , Francis Darrel P. 
Published: January 2016

Background—
Studies of renal denervation report disparate results. Meta-analysis by trial design may allow quantitative estimation of sources and magnitude of biases in denervation studies.

Methods and Results—
One hundred forty nonrandomized, 6 randomized open-label, and 2 randomized blinded studies were analyzed for 2 outcomes: (1) blood pressure changes for nonrandomized, open-label randomized, and blinded studies; and (2) quantification of 3 biases potentially contributing to apparent antihypertensive effects: (a) regression to the mean, (b) asymmetrical data handling, and (c) true blood pressure drops caused by something other than the tested therapy (confounding). Nonrandomized studies and open-label randomized trials reported large reductions in office blood pressure of 23.6 mm Hg (95% confidence interval [CI], 22.0 to 25.3) and 29.1 mm Hg (95% CI, 25.2 to 33.1 mm Hg), respectively. They reported smaller reductions in ambulatory blood pressures (11.2 mm Hg; 95% CI, 10.0 to 12.4). The blinded trials found no significant reduction in blood pressure (2.9 mm Hg; 95% CI, −0.4 to 6.3). Analyses of these data indicate the magnitude of the 3 potential sources of bias to be regression to the mean, −1.01 mm Hg (95% CI, 4.24 to −6.27); asymmetrical data handling, −10.8 mm Hg (95% CI, −8.77 to −12.87); and confounding, −8.3 mm Hg (95% CI, −4.73 to −11.83).

Conclusions—
Increasingly bias-resistant trial designs report effect sizes of decreasing magnitude. This disparity may be caused by asymmetrical data handling and confounding (eg, increased drug adherence). If these differences are caused by trial design and not by some other differences in patients or procedures, which happen to match the trial design, then randomization alone is not enough: blinding is also needed. This has broad implications across trials of medications and devices.
Description of Phasmarhabditis californica n. sp. and first report of P. papillosa (Nematoda: Rhabditidae) from invasive slugs in the USA
Authors: Tandingan De Ley Irma , Holovachov Oleksandr , Mc Donnell Rory J. , Bert Wim , Paine Timothy D. , De Ley Paul 
Published: January 2016

A new species ofPhasmarhabditisand the known speciesP. papillosawere isolated from cadavers of invasive slugs in California.Phasmarhabditis papillosais the type of the genus and has not previously been reported from the Americas. Both species are characterised based on morphology, morphometrics and molecular data. Molecular phylogenies were inferred from concatenated DNA sequence alignments of nearly complete SSU and the D2-D3 domains of the LSU rDNA.Phasmarhabditis californican. sp. is characterised by a robust body, mature egg-laying specimens almost spindle-shaped when relaxed, 1.5 (1.3-1.8) mm long, tapering to a bluntly rounded anterior end with stoma about as long as lip region diam., six inner labial papillae and four outer cephalic papillae, pharynx with rounded to pyriform basal bulb, vulva located halfway along the body, hermaphroditic, didelphic, amphidelphic, and short, conoid tail constricted at one-third its length with prominent phasmids. Not a single male was found among five strains.Phasmarhabditis papillosais gonochoristic and has a longer isthmus, pyriform basal bulb and longer, dome-shaped spicate female tail constricted halfway along its length. Sequence analysis revealed unambiguous autapomorphies forP. papillosaandP. californican. sp. Phylogenetic analyses placed these two species in a monophyletic clade comprisingPhasmarhabditisspecies and other gastropod-parasitic taxa. Morphology, genetic distance, reproductive strategy and nucleotide autapomorphies support the new taxon.
G. J. Billberg’s (1833) ‘On the ichthyology, and description of some new fish species of the pipefish genus Syngnathus’
Authors: KULLANDER SVEN O. 
Published: January 2016

Gustaf Johan Billberg’s review of ichthyology, published in Swedish in 1833 in the Linnéska samfundets handlingar, mentions 92 fish taxa at genus and species level, 41 of which represent new taxa, unnecessary replacement names, or unjustified emendations. Billberg presents his own classification of fishes, in which five new family names are introduced: Ballistidae, Diodontidae, Ooididae, Chironectidae, and Macrorhyncidae. Diodontidae has priority over Diodontidae Bonaparte, 1835. Macrorhyncidae was published earlier than Gempylidae Gill, 1862, but the latter has priority by prevailing usage. Billberg mentions 61 genera of fishes, 41 of them listed only by name. Six generic names proposed by Billberg are available as unjustified emendations: Myxinus, Petromyzus, Scylia, Mustellus, Zyganna, and Ballistes. Brachionus is an unnecessary replacement name. Aphrus, Capriscus, Exormizus, Enneophthalmus, and Oedaus are nomina nuda. Eight new genera of fishes are proposed: Anodon, Posthias, Orbis, Sphaeroides, and Ooides are junior synonyms; Cotilla is a nomen oblitum in relation to Sufflamen Jordan, 1916; Tropigaster a nomen oblitum in relation to Aracana Gray, 1835; and Tetragonizus a nomen oblitum in relation to Lactoria Jordan & Fowler, 1902. Billberg lists 31 species of fishes. Three represent new combinations; two are nomina nuda. The following 14 new species are described based on literature: Raja forskohlii, Cephaloptera dumerillii, Myliobatis lacepedei, Scylia russelii, Anodon macropterus, Cotilla frenata, Monacanthus blochii, M. sebae, M. cuvieri, M. marcgravii, Tetraodon striatus, Orbis psittacinus, Orbis punctulatus, and Orbis guttatus. All of those are invalid, except Scylia russelii, which is a species inquirenda. The following nine species group names are unnecessary replacement names and consequently invalid: Raja arabica, Myliobatis rissoi, Scylia isabellina, Anodon cirrhosus, Anodon cornutus, Zyganna voracissima, Centrina broussonetii, Acipenser vulgaris, and Acipenser ichthyocolla. Three species of pipefishes of the family Syngnathidae are described and figured by Billberg from drawings of specimens observed on the Swedish West Coast. Syngnathus virens and S. pustulatus are junior synonyms of S. typhle Linnaeus, 1758. Syngnathus palmstruchii is a junior synonym of Entelurus aequoreus (Linnaeus, 1758).
Metaethics from a First Person Standpoint
Authors: Wilson Catherine 
Published: January 2016

Metaethics from a First Person Standpoint addresses in a novel format the major topics and themes of contemporary metaethics, the study of the analysis of moral thought and judgement. Metathetics is less concerned with what practices are right or wrong than with what we mean by ‘right’ and ‘wrong.’
Looking at a wide spectrum of topics including moral language, realism and anti-realism, reasons and motives, relativism, and moral progress, this book engages students and general readers in order to enhance their understanding of morality and moral discourse as cultural practices. Catherine Wilson innovatively employs a first-person narrator to report step-by-step an individual’s reflections, beginning from a position of radical scepticism, on the possibility of objective moral knowledge. The reader is invited to follow along with this reasoning, and to challenge or agree with each major point. Incrementally, the narrator is led to certain definite conclusions about ‘oughts’ and norms in connection with self-interest, prudence, social norms, and finally morality. Scepticism is overcome, and the narrator arrives at a good understanding of how moral knowledge and moral progress are possible, though frequently long in coming. Accessibly written, Metaethics from a First Person Standpoint presupposes no prior training in philosophy and is a must-read for philosophers, students and general readers interested in gaining a better understanding of morality as a personal philosophical quest.
Evaluation of a Method to Enhance Real-Time, Ground Radar–Based Rainfall Estimates Using Climatological Profiles of Reflectivity from Space
Authors: Wen Yixin , Kirstetter Pierre , Hong Yang , Gourley Jonathan J. , Cao Qing , Zhang Jian , Flamig Zac , Xue Xianwu 
Published: January 2016

Abstract
Over mountainous terrain, ground weather radars face limitations in monitoring surface precipitation as they are affected by radar beam blockages along with the range-dependent biases due to beam broadening and increase in altitude with range. These issues are compounded by precipitation structures that are relatively shallow and experience growth at low levels due to orographic enhancement. To improve surface precipitation estimation, researchers at the University of Oklahoma have demonstrated the benefits of integrating the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) products into the ground-based NEXRAD rainfall estimation system using a vertical profile of reflectivity (VPR) identification and enhancement (VPR-IE) approach. However, the temporal resolution of TRMM limits the application of VPR-IE method operationally. To implement the VPR-IE concept into the National Mosaic and Multi-Sensor QPE (NMQ) system in real time, climatological VPRs from 11 years of TRMM PR observations have been characterized for different stratiform/convective rain types, seasons, and surface rain intensities. Then, these representative profiles are used to adjust ground radar–based precipitation estimates in the NMQ system based on different precipitation structures. This study conducts a comprehensive evaluation of the newly developed climatological VPR-IE (CVPR-IE) method on winter events (January, February, and December) in 2011. The statistical analysis reveals that the CVPR-IE method provides a clear improvement over the original radar QPE in the NMQ system for the study region. Compared to physically based VPRs from real-time PR measurements, climatological VPRs have limitations in representing precipitation structure for individual events. A hybrid correction scheme incorporating both climatological and real-time VPR information is desired for better skill in the future.
Benchmarking NLDAS-2 Soil Moisture and Evapotranspiration to Separate Uncertainty Contributions
Authors: Nearing Grey S. , Mocko David M. , Peters-Lidard Christa D. , Kumar Sujay V. , Xia Youlong 
Published: January 2016

AbstractModel benchmarking allows us to separate uncertainty in model predictions caused by model inputs from uncertainty due to model structural error. This method is extended with a “large sample” approach (using data from multiple field sites) to measure prediction uncertainty caused by errors in 1) forcing data, 2) model parameters, and 3) model structure, and use it to compare the efficiency of soil moisture state and evapotranspiration flux predictions made by the four land surface models in phase 2 of the North American Land Data Assimilation System (NLDAS-2). Parameters dominated uncertainty in soil moisture estimates and forcing data dominated uncertainty in evapotranspiration estimates; however, the models themselves used only a fraction of the information available to them. This means that there is significant potential to improve all three components of NLDAS-2. In particular, continued work toward refining the parameter maps and lookup tables, the forcing data measurement and processing, and also the land surface models themselves, has potential to result in improved estimates of surface mass and energy balances.
The Intermediate Complexity Atmospheric Research Model (ICAR)
Authors: Gutmann Ethan , Barstad Idar , Clark Martyn , Arnold Jeffrey , Rasmussen Roy 
Published: January 2016

Abstract
With limited computational resources, there is a need for computationally frugal models. This is particularly the case for atmospheric sciences, which have long relied on either simplistic analytical solutions or computationally expensive numerical models. The simpler solutions are inadequate for many problems, while the cost of numerical models makes their use impossible for many problems, most notably high-resolution climate downscaling applications spanning large areas, long time periods, and many global climate projections. Here the Intermediate Complexity Atmospheric Research model (ICAR) is presented to provide a new step along the modeling complexity continuum. ICAR leverages an analytical solution for high-resolution perturbations to wind velocities, in conjunction with numerical physics schemes, that is, advection and cloud microphysics, to simulate the atmosphere. The focus of the initial development of ICAR is for predictions of precipitation, and eventually temperature, humidity, and radiation at the land surface. Comparisons between ICAR and the Weather Research and Forecasting (WRF) Model for simulations over an idealized mountain are presented, as well as among ICAR, WRF, and the Parameter-Elevation Regressions on Independent Slopes Model (PRISM) observation-based product for a year-long simulation over the Colorado Rockies. In the ideal simulations, ICAR matches WRF precipitation predictions across a range of environmental conditions with a coefficient of determination r2 of 0.92. In the Colorado Rockies, ICAR, WRF, and PRISM show very good agreement, with differences between ICAR and WRF comparable to the differences between WRF and PRISM in the cool season. For these simulations, WRF required 140–800 times more computational resources than ICAR.
EUMETSAT Global AVHRR Wind Product
Authors: Borde Régis , Hautecoeur Olivier , Carranza Manuel 
Published: January 2016

AbstractEUMETSAT has been deriving atmospheric motion vectors (AMV) operationally from the EUMETSAT Polar System satellite MetOp over polar regions since 2011. The launch of MetOp-B in 2012 permitted doubling the frequency of extracting AMVs using AVHRR imagery data of both MetOp-A and -B satellites. The tandem configuration with two satellites on the same orbital plane, but with a phase difference, provided an interesting opportunity to create global AMVs from the satellites with a significant overlap in imagery data. EUMETSAT has therefore developed a new global AVHRR winds product derived from a pair of MetOp-A and MetOp-B images that has been operational since January 2015. The temporal gap between the two images used for tracking clouds is about 50 min. The global coverage of this new wind product allows for a homogeneous retrieval of wind product over the whole globe, including the polar regions. This clearly helps fill the gaps between 55° and 70° latitude north and south, where only few wind observations are currently available for assimilation into numerical weather prediction models. The new global AVHRR wind product can be directly compared with AMVs derived from geostationary satellites. This paper describes the scientific concept of wind extraction using dual MetOp satellites. It highlights the performance of the new global AVHRR wind product by comparing with collocated AMVs extracted from the EUMETSAT geostationary satellites Meteosat-7 and Meteosat-10.