bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-232: A novel approach for liquid biopsy by using nExo
Authors: Yokoi Akira , Villar-Prados Alejandro , Oliphint Paul Allen , O'Halloran Theresa J. , Roszik Jason , Sood Anil K. 
Published: August 2019

Abstract
Exosomes are small extracellular vesicles secreted from all living cells; its contents are highly varied, including proteins, small RNAs and recently discovered, genomic DNA (gDNA). The presence of nuclear content in exosomes suggests that different cell compartments can contribute to exosome cargo; however, little is known about this sub population of nuclear derived exosomes (nExo). Here, we analyzed nExo isolated from ovarian cancer cells and characterized them to explore potential clinical relevance such as cancer detection and therapeutic response. Exosomes were isolated from ovarian cancer cell lines, normal human fallopian epithelial tube cells and bio-fluids from mouse and human samples. To determine the purity of exosomes, nanoparticle tracking system, immunoblotting assay and cryo-transmission electron microscopy were used. To analyze the content of exosomes, protein mass spectrometry and imaging flow cytometry analysis was performed. First, we determined that mass spectrometry analyses for ovarian cancer cell exosomes revealed that 12.5% of proteins are derived from the cell nucleus sub-population. Additionally, using a novel imaging flow cytometry technique which enables us to identify single exosome and to quantify them, we determined that 10% of exosomes carried gDNA. Conversely, normal cells secreted only 0.2% of nExo. Then we hypothesized that the prevalence of gDNA is affected by genotoxic drugs. Treating cells with either the PARP inhibitor olaparib or topoisomerase inhibitor topotecan increased the proportion of nExo secreted from ovarian cancer cells. In addition, PARP proteins exist in ovarian cancer cell exosomes and 80.4 % of the exosome co-localized with gDNA. Using in vivo preclinical models, serum from ovarian cancer bearing mice contained a higher number of nExo than non-tumor controls, and this population was increased in response to treatment of genotoxic drugs. Furthermore, plasma and ascites from ovarian cancer patients contain around 0.3 % of nExo, which include nuclear proteins and gDNA. We demonstrate that nExo are predominantly secreted from cancer cells and could serve as an important biomarker. Although the subpopulation is relatively rare, their presence in bio-fluids isolated from cancer patients holds the potential of serving as novel biomarkers for early detection and therapeutic response to genotoxic agents.
Citation Format: Akira Yokoi, Alejandro Villar-Prados, Paul Allen Oliphint, Theresa J. O'Halloran, Jason Roszik, Anil K. Sood. A novel approach for liquid biopsy by using nExo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-232.
Abstract LB-288: CDC7 kinase inhibition by SRA141 induces a potentially novel caspase-dependent tumor cell apoptosis associated with altered DNA replication and cell cycle dynamics
Authors: Jagannathan Veena , Milutinovic Snezana , Hansen Ryan , Strouse Bryan , Hassig Christian , Brown Eric 
Published: August 2019

Abstract
DNA replication is a tightly regulated process required for faithful duplication of the genome. Previous research in lower eukaryotes has demonstrated a requisite role for the CDC7 protein kinase in DNA replication origin firing through phosphorylation of the MCM2-7 helicase complex. Owing to its overexpression in various neoplasms, CDC7 has emerged as an attractive target for cancer treatment. We previously reported that SRA141, a potent and selective CDC7 inhibitor, is cytotoxic to multiple tumor cell lines in vitro and demonstrates robust anti-tumor efficacy in colorectal and leukemia xenograft models. Here, we explored the effects of SRA141 on DNA replication and cell cycle dynamics and how these effects relate to the mechanism of SRA141-induced cell death in colorectal cancer cell lines.
SRA141 treatment caused a complete inhibition of MCM2 phosphorylation and reduced overall cellular DNA synthesis within 3 hours, with the greatest effects observed in late S-phase. Unexpectedly, DNA combing experiments indicated that SRA141 caused a 70-90% increase in the rate of replication fork progression. These findings suggest that SRA141 may indeed limit origin firing, but this effect is compensated for in part by increased replication fork rates. Despite delay, nucleotide analog pulse-chase experiments indicated that SRA141 treated cells ultimately finished S phase and transitioned into mitosis. In contrast to other reports, no evidence of replication fork collapse was observed, indicating that the main mechanism of SRA141 cytotoxicity is not mediated through replication fork collapse. Intriguingly, some of the most pronounced effects of SRA141 treatment were on progression through M phase, as evidenced by an accumulation of mitotic cells and increased Cyclin B levels following treatment. Moreover, inhibition of Aurora B kinase, which regulates mitotic progression, strongly synergized with SRA141 in caspase-dependent cancer cell killing. Taken together, our findings indicate that the mechanism of cytotoxicity of CDC7 inhibitors is distinct from agents that cause replication fork collapse or inhibit CDKs, and thus may define a new class of cancer therapeutic agents that synergize with drugs that target certain mitotic pathways.
Citation Format: Veena Jagannathan, Snezana Milutinovic, Ryan Hansen, Bryan Strouse, Christian Hassig, Eric Brown. CDC7 kinase inhibition by SRA141 induces a potentially novel caspase-dependent tumor cell apoptosis associated with altered DNA replication and cell cycle dynamics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-288.
Abstract LB-302: Whole genome sequencing reveals a significant role of ZNFs-PHLPP2-AKT axis in familial breast cancer of chaoshan area
Authors: Fang Can-Bin , Ye Qian-Qian , Liu Jing , Zhang Guo-Jun 
Published: August 2019

Abstract
Introduction Up to 15% cases of breast cancer are familial. However, the two most prevalent susceptibility genes, BRCA1 and BRCA2, only account for 25% of the familial cases. To this regard, we aimed to identify recurrent variants associated with familial breast cancer in Chaoshan Area of China by whole genome sequencing.
Materials & Methods In the present study, Whole Genome Sequencing was performed in 8 familial breast cancer families with 13 familial breast cancer cases and 25 healthy relatives from Chaoshan Area. All the variants were filtered and prioritized by co-segregation analysis and bioinformatic tools.
Results A total of 714 variants in 609 genes were selected as rare, probably damaging pathogenic mutations after co-segregation and functional prediction analysis in each family. In all the 609 genes, the zinc finger protein family was overlapped in all the 8 families, among which the c.120-130del of ZNF77 was overlapped in 3 families, c.279_791de of ZNF544 and c.T895A of ZNF479 in 2 families respectively, which emphasized the great significance of ZNF family in the mutational spectrum of Chaoshan Area. After that, the KEGG Pathway analysis in KOBAS 3.0 implied the significance of PI3K-Akt pathway in all the mutated 609 genes. At the same time, the PPI analysis by Cytoscape 3.6.1 indicated that all ZNF genes were interacted with one specific gene, PHLPP2, which inhibits the PI3K-Akt pathway similar to PTEN. Furthermore, two website-based bioinformatic tools cBioportal and Oncomine have predicted the positive correlations between ZNF77 and PHLPP2. All the analysis above was demonstrated the great significance of ZNFs-PHLPP2-AKT axis in the mutational spectrum of familial breast cancer of Chaoshan Area, in China.
Conclusions Zinc finger protein family, especially ZNF77, are frequently mutated in the familial breast cancer of Chaoshan Area, which results in the down regulation of PHLPP2 and subsequently reverse the inhibition of PI3K-Akt pathway, and finally lead to tumorigenesis.
Citation Format: Can-Bin Fang, Qian-Qian Ye, Jing Liu, Guo-Jun Zhang. Whole genome sequencing reveals a significant role of ZNFs-PHLPP2-AKT axis in familial breast cancer of chaoshan area [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-302.
Cardiac Magnetic Resonance Left Ventricular Mechanical Uniformity Alterations for Risk Assessment After Acute Myocardial Infarction
Authors: Stiermaier Thomas , Backhaus Sören J. , Lange Torben , Koschalka Alexander , Navarra Jenny‐Lou , Boom Patricia , Lamata Pablo , Kowallick Johannes T. , Lotz Joachim , Gutberlet Matthias , de Waha‐Thiele Suzanne , Desch Steffen , Hasenfuß Gerd , Thiele Holger , Eitel Ingo , Schuster Andreas 
Published: August 2019

Background

Despite limitations as a stand‐alone parameter, left ventricular (LV) ejection fraction is the preferred measure of myocardial function and marker for postinfarction risk stratification.
LV
myocardial uniformity alterations may provide superior prognostic information after acute myocardial infarction, which was the subject of this study.

Methods and Results

Consecutive patients with acute myocardial infarction (n=1082; median age: 63 years; 75% male) undergoing cardiac magnetic resonance at a median of 3 days after infarction were included in this multicenter observational study. Circumferential and radial uniformity ratio estimates were derived from cardiac magnetic resonance feature tracking as markers of mechanical uniformity alterations (values between 0 and 1 with 1 reflecting perfect uniformity). The clinical end point was the 12‐month rate of major adverse cardiac events, consisting of all‐cause death, reinfarction, and new congestive heart failure. Patients with major adverse cardiac events (n=73) had significantly impaired circumferential uniformity ratio estimates (0.76 [interquartile range: 0.67–0.86] versus 0.84 [interquartile range: 0.76–0.89];
P
<0.001) and radial uniformity ratio estimates (0.69 [interquartile range: 0.60–0.79] versus 0.76 [interquartile range: 0.67–0.83];
P
<0.001) compared with patients without events. Although uniformity estimates did not provide independent prognostic information in the overall cohort, a circumferential uniformity ratio estimate below the median of 0.84 emerged as an independent predictor of outcome in postinfarction patients with LV ejection fraction >35% (n=959), even after adjustment for established risk factors (hazard ratio: 1.99; 95% CI, 1.06–3.74;
P
=0.033 in multivariable Cox regression analysis). In contrast, LV ejection fraction was not associated with adverse events in this subgroup of patients with acute myocardial infarction.

Conclusions
Cardiac magnetic resonance–derived estimates of mechanical uniformity alterations are novel markers for risk assessment after acute myocardial infarction, and the circumferential uniformity ratio estimate provides independent prognostic information for patients with preserved or only moderately reduced LV ejection fraction.
Cave hominem
Authors: McGrath Sean E. 
Published: August 2019

Abstract
This article explores two episodes from Pseudo-Oppian’s Cynegetica which both feature domestic animals: the horse in 1.239-270 and the dog in 4.354-376. Both of these episodes are highly intertextual, alluding to, respectively, Sophocles’ Oedipus Tyrannus and the abduction narratives from Moschus’ Europa and the Homeric Hymn to Demeter. I argue that the poet of the Cynegetica invites his readers to reflect on the potentially problematic nature of the power dynamic for these animals through sophisticated allusions to the poetic tradition, through which the relationship between man and animal is compared to that between the gods and humans.
The Role of Central Asia in the “One Belt—One Road” Initiative
Authors: Kokushkina Irina V. , Soloshcheva Maria A. 
Published: August 2019

The “New Silk Road” or “One Belt–One Road” (also “Belt and Road”) is a global project initiated by China, the implementation of which affects various areas of development of many states and regions of the world, including security issues, socio-cultural, political, diplomatic and civilisational aspects.
A total of 173 agreements with 125 states and 29 international organisations have been signed under this initiative. The project is gaining momentum every year and attracts ever more researchers who analyse the economic, political, and cultural sides of the project and the interaction of the different countries and regions with China within the framework of this global enterprise. This article assesses the participation of five Central Asian countries (Kazakhstan, Kyrgyzstan, Tajikistan, Uzbekistan, and Turkmenistan) in the Chinese project and aims to define the mutual interests of the parties on the basis of economic indicators (i.e., ESI, RCA, TDC, and G-L indexes).
A Time-Varying Causality Formalism Based on the Liang–Kleeman Information Flow for Analyzing Directed Interactions in Nonstationary Climate Systems
Authors: Tawia Hagan Daniel Fiifi , Wang Guojie , San Liang X. , Dolman Han A. J. 
Published: August 2019

AbstractThe interaction between the land surface and the atmosphere is of significant importance in the climate system because it is a key driver of the exchanges of energy and water. Several important relations to heat waves, floods, and droughts exist that are based on the interaction of soil moisture and, for instance, air temperature and humidity. Our ability to separate the elements of this coupling, identify the exact locations where they are strongest, and quantify their strengths is, therefore, of paramount importance to their predictability. A recent rigorous causality formalism based on the Liang–Kleeman (LK) information flow theory has been shown, both theoretically and in real-world applications, to have the necessary asymmetry to infer the directionality and magnitude within geophysical interactions. However, the formalism assumes stationarity in time, whereas the interactions within the land surface and atmosphere are generally nonstationary; furthermore, it requires a sufficiently long time series to ensure statistical sufficiency. In this study, we remedy this difficulty by using the square root Kalman filter to estimate the causality based on the LK formalism to derive a time-varying form. Results show that the new formalism has similar properties compared to its time-invariant form. It is shown that it is also able to capture the time-varying causality structure within soil moisture–air temperature coupling. An advantage is that it does not require very long time series to make an accurate estimation. Applying a wavelet transform to the results also reveals the full range of temporal scales of the interactions.
Weakened Impact of the Developing El Niño on Tropical Indian Ocean Climate Variability under Global Warming
Authors: He Chao , Wang Yuhao , Li Tim 
Published: August 2019

AbstractEl Niño induces an anomalous easterly wind along the equator and a pair of anomalous anticyclones straddling the equator over the tropical Indian Ocean (TIO) during the autumn of its developing phase. Based on 30 coupled models participating in CMIP5, these atmospheric circulation anomalies over TIO are substantially weakened by about 12%–13% K−1 under global warming scenarios, associated with a weakened zonal gradient of the sea surface temperature (SST) anomaly. The mechanism for the response is investigated based on a hierarchy of model experiments. Based on stand-alone atmospheric model experiments under uniform and patterned mean-state SST warming, the atmospheric circulation anomaly over TIO during the autumn of the developing El Niño is also substantially weakened by about 8% K−1 even if the interannual variability of SST remains exactly unchanged, suggesting that the primary cause resides in the atmosphere rather than the SST anomaly. The tropospheric static stability is robustly enhanced under global warming, and experiments performed by a linear baroclinic model show that a much weaker atmospheric circulation anomaly over TIO is stimulated by an unchanged diabatic heating anomaly under a more stable atmosphere. The weakened atmospheric circulation anomaly due to enhanced static stability weakens the zonal gradient of the SST anomaly within TIO through local air–sea interaction, and it acts to further weaken the atmospheric circulation anomaly. The enhanced static stability of the troposphere is probably the primary cause and the air–sea interaction within TIO is a secondary cause for the weakened impact of the developing El Niño on atmospheric circulation variability over TIO.
Long-Term Retrievals of Cloud Type and Fair-Weather Shallow Cumulus Events at the ARM SGP Site
Authors: Sunny Lim Kyo-Sun , Riihimaki Laura D. , Shi Yan , Flynn Donna , Kleiss Jessica M. , Berg Larry K. , Gustafson William I. , Zhang Yunyan , Johnson Karen L. 
Published: August 2019

AbstractA long-term climatology of classified cloud types has been generated for 13 years (1997–2009) over the Atmospheric Radiation Measurement (ARM) Southern Great Plains (SGP) site for seven cloud categories: low clouds, congestus, deep convection, altocumulus, altostratus, cirrostratus/anvil, and cirrus. The classification was based on the cloud macrophysical quantities of cloud top, cloud base, and physical thickness of cloud layers, as measured by active sensors such as the millimeter-wavelength cloud radar (MMCR) and micropulse lidar (MPL). Climate variability of cloud characteristics has been examined using the 13-yr cloud-type retrieval. Low clouds and cirrus showed distinct diurnal and seasonal cycles. Total cloud occurrence followed the variation of low clouds, with a diurnal peak in early afternoon and a seasonal maximum in late winter. Additionally, further work has been done to identify fair-weather shallow cumulus (FWSC) events for 9 years (2000–08). Periods containing FWSC, a subcategory of clouds classified as low clouds, were produced using cloud fraction information from a total-sky imager and ceilometer. The identified FWSC periods in our study show good agreement with manually identified FWSC, missing only 6 cases out of 70 possible events during the spring to summer seasons (May–August).
Intermittency in Estuarine Turbulence: A Framework toward Limiting Bias in Microstructure Measurements
Authors: Huguenard Kimberly , Bears Kris , Lieberthal Brandon 
Published: August 2019

AbstractIntermittent turbulence behavior has a number of implications for field sampling, namely, that if undersampled, it can result in over- or underestimates of turbulent kinetic energy (TKE) dissipation rates. Sampling thresholds and common distributions have previously been defined for oceanic environments, but estuaries remain relatively underrepresented. Utilizing vertical microstructure profilers is a robust way to directly measure TKE dissipation rates; however, microstructure sensors are delicate and conducting a limited number of profiles in a burst is desirable. In this work, a statistical framework is used to characterize intermittency in a partially mixed estuary. In particular, a multiple comparison test is proposed to evaluate the number of profiles required to sufficiently represent TKE dissipation averages. The technique is tested on a microstructure dataset from the Damariscotta River in Maine, which covers seasonal and fortnightly time scales. The Damariscotta River features a variety of bathymetric and channel complexities, which provide the opportunity to examine intermittency as it relates to different processes. Small-scale intermittency is prominent during stratified conditions in shallow locations as well as near channel-shoal morphology, channel bends, and constrictions.
Influences of Horizontal Grid Spacing and Microphysics on WRF Forecasts of Convective Morphology Evolution for Nocturnal MCSs in Weakly Forced Environments
Authors: Thielen Jonathan E. , Gallus William A. 
Published: August 2019

Abstract
Nocturnal mesoscale convective systems (MCSs) are important phenomena because of their contributions to warm-season precipitation and association with severe hazards. Past studies have shown that their morphology remains poorly forecast in current convection-allowing models operating at 3–4-km horizontal grid spacing. A total of 10 MCS cases occurring in weakly forced environments were simulated using the Weather Research and Forecasting (WRF) Model at 3- and 1-km horizontal grid spacings to investigate the impact of increased resolution on forecasts of convective morphology and its evolution. These simulations were conducted using four microphysics schemes to account for additional sensitivities to the microphysical parameterization. The observed and corresponding simulated systems were manually classified into detailed cellular and linear modes, and the overall morphology depiction and the forecast accuracy of each model configuration were evaluated. In agreement with past studies, WRF was found to underpredict the occurrence of linear modes and overpredict cellular modes at 3-km horizontal grid spacing with all microphysics schemes tested. When grid spacing was reduced to 1 km, the proportion of linear systems increased. However, the increase was insufficient to match observations throughout the evolution of the systems, and the accuracy scores showed no statistically significant improvement. This suggests that the additional linear modes may have occurred in the wrong subtypes, wrong systems, and/or at the wrong times. Accuracy scores were also shown to decrease with forecast length, with the primary decrease in score generally occurring during upscale growth in the early nocturnal period.
Surveillance, Epidemiology, and Estimated Burden of Neonatal Abstinence Syndrome, Tennessee, 2013-2016
Authors: Brennan Julia , Wiedeman Caleb , Dunn John R. , Schaffner William , Jones Timothy F. 
Published: August 2019

Objectives: Between 2003 and 2013, the rate of neonatal abstinence syndrome (NAS)—a postnatal drug withdrawal syndrome—in Tennessee increased approximately 10-fold. NAS surveillance is relatively new, and underestimation associated with surveillance has not been described. We compared data from the Tennessee NAS public health surveillance system (TNSS) with a second source of NAS data, hospital discharge data system (HDDS), and estimated the true number of infants with NAS using capture-recapture methods. Methods: We obtained NAS data on cases of NAS among Tennessee infants from TNSS and HDDS from January 1, 2013, through December 31, 2016. We matched cases of NAS identified in TNSS to cases identified in HDDS. We estimated the true number of infants with NAS by using the Lincoln-Peterson estimator capture-recapture methodology. Results: During the study period, 4070 infants with NAS were reported to TNSS, and 5321 infants with NAS were identified in HDDS; 2757 were in both data sets. Using capture-recapture methods, the total estimated number of infants with NAS during the study period was 7855 (annual mean = 1972; estimated range = 1531-2427), which was 93% more than in TNSS and 48% more than in HDDS. Drugs used for the medication-assisted treatment of substance use disorder were the most commonly reported substances associated with NAS (n = 2389, 59%). Conclusions: TNSS underestimated the total burden of NAS based on the capture-recapture estimate. Case-based public health surveillance is important for monitoring the burden of and risk factors for NAS and helping guide public health interventions.