bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B73: Pancreatic stellate cell heterogeneity in cancer
Authors: Öhlund Daniel , Handly-Santana Abram , Elyada Ela , Biffi Giulia , Tuveson David A. 
Published: December 2016

Abstract
Paracrine interactions between pancreatic stellate cells (PSCs) and tumor cells play key roles in pancreatic cancer tumorigenesis. However, attempts to therapeutically target the PSCs have implied that PSCs may also restrain tumor growth, raising the possibility of diverse and dynamic pathophysiological roles of these cells in cancer. In order to gain a deeper understanding of the functional heterogeneity found among PSCs, we have developed an organotypic co-culture system that allows the study of functional interactions between pancreatic tumor-derived organoids and PSCs in a three-dimensional basement membrane matrix (Matrigel). PSCs embedded in Matrigel acquire a quiescent phenotype and restore their vitamin A droplets similar to PSCs found in healthy pancreata in vivo. In co-culture the PSCs proliferate, form lattices around the organoids, and secrete extracellular matrix proteins and inflammatory cytokines. In turn, the organoids proliferate more rapidly in co-culture with PSCs compared to their mono-cultured counterparts, as well as survive passaging in reduced media conditions.
Furthermore, we show that PSCs can differentiate into two distinct subtypes with different phenotypic features depending on the spatial proximity to the co-cultured organoids. PSCs found in direct contact with tumor cells express higher levels of smooth muscle actin (SMA), while PSCs that are more distant from the tumor cells show low SMA expression and gain a secretory phenotype. The secreted factors from this subtype of PSCs activate signaling pathways important for survival and proliferation in tumor organoids. We demonstrate that these two subtypes are mutually exclusive, and can both be found in vivo with similar spatial distribution as seen in the co-culture system.
Taken together, we have identified two subtypes of PSCs present in pancreatic cancer with potentially different pathophysiological functions. Preferentially targeting one of these subtypes in future clinical trials may positively affect patient outcomes.
Citation Format: Daniel Öhlund, Abram Handly-Santana, Ela Elyada, Giulia Biffi, David A. Tuveson.{Authors}. Pancreatic stellate cell heterogeneity in cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B73.
Abstract IA06: Serum contains enough information for early detection of pancreatic cancer
Authors: Borrebaeck Carl A. K. 
Published: December 2016

Abstract
One of the driving forces in personalized medicine is the search for protein patterns that can be utilized for improved diagnosis, assessing the risk for tumor relapse and disease progression. Affinity proteomics, a high-throughput technology for protein expression profiling, is now generating data for improved diagnosis and patient stratification, which has been demonstrated in several clinical studies. Pancreatic ductal adenocarcinoma (PDAC) is such a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. Based on multiparametric microarray analysis of over 2500 patient samples, serum protein signatures have for the first time been identified that could discriminate between pancreatic cancer patients with stage I, II, III and IV, which indicates a possibility for early diagnosis and an increased detection rate of surgically resectable tumors, which significantly would increase the life expectancy of pancreatic cancer patients.
Citation Format: Carl A. K. Borrebaeck.{Authors}. Serum contains enough information for early detection of pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA06.
Abstract PR05: Genome-scale CRISPR-Cas9 screening to identify essential genes and pathways in pancreatic cancer
Authors: Aguirre Andrew J. , Shao Wei , Xu Han , Weir Barbara , Vazquez Francisca , Meyers Robin , Zhang Cheng-Zhong , Doshi Mihir , Cowley Glenn S. , Ewachiw Theodore , Rasheed Zeshaan , Golub Todd R. , Stegmaier Kimberly , Roberts Charles W. , Garraway Levi A. , Meyerson Matthew , Tsherniak Aviad , Root David E. , Espenshade Peter J. , Hahn William C. 
Published: December 2016

Abstract
Loss-of-function genetic screens in cancer cell lines permit the systematic interrogation of genes and pathways involved in cell proliferation and viability. The CRISPR-Cas9 system enables effective genome editing for perturbation of gene function. To identify genes that are essential for cancer cell proliferation and survival, we have optimized an approach for efficient genome-scale CRISPR-Cas9 pooled screening and performed negative-selection knock-out screens in 43 human cancer cell lines with diverse genetic and phenotypic features, including 8 pancreatic cancer cell lines. We report that CRISPR-Cas9 efficacy varies depending on the cell context and propose methods to effectively identify differential cancer dependencies across cell lines. Additionally, we identify a strong correlation between genomic copy number and perceived gene dependency, and further elucidate a gene-independent effect of CRISPR-Cas9 cutting. Using these screening data, we performed a detailed interrogation of gene and pathway dependencies in pancreatic cancer. Through integrative analysis of CRISPR-Cas9 screening results with RNA-interference and small molecule screening data, as well as DNA and RNA sequencing, we identified a high-confidence set of recurrently essential genes in pancreatic cancer, including several with associated biomarkers. Moreover, through pathway analyses of CRISPR-Cas9 screening data, we have identified a number of essential biologic processes including key metabolic and cell signaling pathways that may represent potential therapeutic avenues. In particular, we characterize the sterol regulatory element binding protein (SREBP) signaling pathway as a recurrent vulnerability in pancreatic cancer and credential this pathway as a potential therapeutic target.
This abstract is also being presented as Poster A13
Citation Format: Andrew J. Aguirre, Wei Shao, Han Xu, Barbara Weir, Francisca Vazquez, Robin Meyers, Cheng-Zhong Zhang, Mihir Doshi, Glenn S. Cowley, Theodore Ewachiw, Zeshaan Rasheed, Todd R. Golub, Kimberly Stegmaier, Charles W. Roberts, Levi A. Garraway, Matthew Meyerson, Aviad Tsherniak, David E. Root, Peter J. Espenshade, William C. Hahn.{Authors}. Genome-scale CRISPR-Cas9 screening to identify essential genes and pathways in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr PR05.
Endotoxaemia-augmented murine venous thrombosis is dependent on TLR-4 and ICAM-1, and potentiated by neutropenia
Authors: Obi Andrea T. , Andraska Elizabeth , Kanthi Yogendra , Kessinger Chase W. , Elfline Megan , Luke Cathy , Siahaan Teruna J. , Jaffer Farouc A. , Wakefield Thomas W. , Henke Peter K. 
Published: December 2016

SummaryVenous thromboembolism is a major cause of death during and immediately post-sepsis. Venous thrombosis (VT) is mediated by cell adhesion molecules and leukocytes, including neutrophil extracellular traps (NETs). Sepsis, or experimentally, endotoxaemia, shares similar characteristics and is modulated via toll like receptor 4 (TLR4). This study was undertaken to determine if endotoxaemia potentiates early stasis thrombogenesis, and secondarily to determine the role of VT TLR4, ICAM-1 and neutrophils (PMNs). Wild-type (WT), ICAM-1-/- and TLR4-/- mice underwent treatment with saline or LPS (10 mg/kg i.p.) alone, or followed by inferior vena cava (IVC) ligation to generate stasis VT. In vivo microscopy of leukocyte trafficking was performed in non-thrombosed mice, and tissue and plasma were harvested during early VT formation. Pre-thrombosis, circulating ICAM-1 was elevated and increased leukocyte adhesion and rolling occurred on the IVC of LPS-treated mice. Post-thrombosis, endotoxaemic mice formed larger, platelet-poor thrombi. Endotoxaemic TLR4-/- mice did not have an augmented thrombotic response and exhibited significantly decreased circulating ICAM-1 compared to endotoxaemic WT controls. Endotoxaemic ICAM-1-/- mice had significantly smaller thrombi compared to controls. Hypothesising that PMNs localised to the inflamed endothelium were promoting thrombosis, PMN depletion using anti-Ly6G antibody was performed. Paradoxically, VT formed without PMNs was amplified, potentially related to endotoxaemia induced elevation of PAI-1 and circulating FXIII, and decreased uPA. Endotoxaemia enhanced early VT occurs in a TLR-4 and ICAM-1 dependent fashion, and is potentiated by neutropenia. ICAM-1 and/or TLR-4 inhibition may be a unique strategy to prevent sepsis-associated VT.Supplementary Material to this article is available online at www.thrombosis-online.com.
Prognostic significance of tPA/PAI-1 complex in patients with heart failure and preserved ejection fraction
Authors: Koller Lorenz , Sulzgruber Patrick , Scharnagl Hubert , Delgado Graciela , Goliasch Georg , März Winfried , Winter Max-Paul , Kleber Marcus E. , Niessner Alexander 
Published: December 2016

SummaryHeart failure with preserved ejection fraction (HFpEF) represents a major epidemic, clinical and public health problem with rising patient numbers every year. Traditional markers for heart failure have been shown to be of limited sensitivity in patients with HFpEF, as those do not reflect pathophysiology of the disease properly. Dysregulation of haemostasis is thought to be central for the initiation and progression of HFpEF. For this reason, we aimed to assess markers of fibrinolytic activity as potential biomarkers for risk assessment in patients with HFpEF. We evaluated blood coagulation parameters in 370 patients with HFpEF included in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. Within an observation period of 9.7 years, 40 percent of these patients died from any cause. tPA/PAI-1 complex significantly predicted all-cause mortality with a hazard ratio (HR) of 1.24 (95 % confidence interval [CI] 1.04–1.47) per increase of 1 SD and cardiovascular mortality with a HR 1.26 (95 % CI 1.02–1.56) per increase of 1 SD. Both associations remained significant after adjustment for cardiovascular risk factors, N-terminal pro–B-type natriuretic peptide (NT-proBNP) and frequent HFpEF- related comorbidities. Importantly, tPA/PAI-1 complex had additional prognostic value above and beyond NT-proBNP as indicated by integrated discrimination improvement (0.0157, p=0.017). In conclusion, the concentration of tPA/ PAI-1 complex is an independent predictor of mortality from all causes and from cardiovascular causes in patients with HFpEF. The concomitant measurement of tPA/PAI-1 complex might be useful in clinical practice to add prognostic value to traditional markers of heart failure.
Atherosclerosis revisited from a clinical perspective: still an inflammatory disease?
Authors: Santovito Donato , Weber Christian 
Published: December 2016

SummaryCompelling experimental results have substantiated the immune-driven inflammatory nature of atherosclerosis. Most of the scientific advances over the past decades have been achieved by relying on transgenic animal models that have been employed with increasing levels of sophistication. However, recent failures in translating various anti-inflammatory therapeutic strategies for use in humans might raise some skepticism with regards to an inflammatory causality underlying human atherosclerosis. By applying a dialectical approach, this Perspective aims to challenge and deduce the nature of atherosclerosis by reviewing results exclusively derived from human studies and recent clinical trials, as “things may not always be, what they appear”.Note: The review process for this manuscript was fully handled by Gregory Y. H. Lip, Editor in Chief.
Marital History and Survival After Stroke
Authors: Dupre Matthew E. , Lopes Renato D. 
Published: December 2016

Background
Stroke is among the leading causes of disability and death in the United States, and nearly 7 million adults are currently alive after experiencing a stroke. Although the risks associated with having a stroke are well established, we know surprisingly little about how marital status influences survival in adults with this condition. This study is the first prospective investigation of how marital history is related to survival after stroke in the United States.

Methods and Results

Data from a nationally representative sample of older adults who experienced a stroke (n=2351) were used to examine whether and to what extent current marital status and past marital losses were associated with risks of dying after the onset of disease. Results showed that the risks of dying following a stroke were significantly higher among the never married (hazard ratio [
HR
], 1.71; 95%
CI
, 1.31–2.24), remarried (
HR
, 1.23; 95%
CI
, 1.06–1.44), divorced (
HR
, 1.23; 95%
CI
, 1.01–1.49), and widowed (
HR
, 1.25; 95%
CI
, 1.10–1.43) relative to those who remained continuously married. We also found that having multiple marital losses was especially detrimental to survival—regardless of current marital status and accounting for multiple socioeconomic, psychosocial, behavioral, and physiological risk factors.

Conclusions
Marital history is significantly associated with survival after stroke. Additional studies are needed to further examine the mechanisms contributing to the associations and to better understand how this information can be used to personalize care and aggressively treat vulnerable segments of the population.
Hotspots of mite new species discovery: Sarcoptiformes (2013–2015)
Authors: LI GUANG-YUN , ZHANG ZHI-QIANG 
Published: December 2016

A list of of type localities and depositories of new species of the mite order Sarciptiformes published in two journals (Zootaxa and Systematic & Applied Acarology) during 2013–2015 is presented in this paper, and trends and patterns of new species are summarised. The 242 new species are distributed unevenly among 50 families, with 62% of the total from the top 10 families. Geographically, these species are distributed unevenly among 39 countries. Most new species (72%) are from the top 10 countries, whereas 61% of the countries have only 1–3 new species each. Four of the top 10 countries are from Asia (Vietnam, China, India and The Philippines).
Gradients of Atmospheric Temperature and Humidity Controlled by Local Urban Land-Use Intensity in Boston
Authors: Wang J. A. , Hutyra L. R. , Li D. , Friedl M. A. 
Published: December 2016

AbstractCities are home to the majority of humanity. Therefore, understanding the mechanisms that control urban climates has substantial societal importance to a variety of sectors, including public health and energy management. In this study, data from an urban sensor network (25 stations) and moderate-resolution remote sensing were used to explore how spatial variation in near-surface air temperature Ta, vapor pressure deficit (VPD), and land surface temperature (LST) depend on local variations in urban land use, both diurnally and seasonally, in the Boston, Massachusetts, metropolitan area. Positive correlations were observed between the amount of local impervious surface area (ISA) and both Ta and VPD. Heat-island effects peaked during the growing-season nighttime, when mean Ta and VPD increased by up to 0.02°C and 0.008 kPa, respectively, per unit ISA. Air temperature and VPD were strongly coupled, but their relationship exhibited significant diurnal hysteresis during the growing season, with changes in VPD generally preceding changes in Ta. Over 79% of the urban–rural difference in VPD was explained by differences in near-surface atmospheric water content, which the authors attribute to reduced evapotranspiration from lower canopy cover in Boston’s urban core. Changes in daytime heat-island intensity were mediated by seasonal feedbacks between vegetation transpiration and VPD forcing. Differences between LST and Ta showed weaker coupling in highly urbanized areas than in rural areas, with summertime surface-urban-heat-island intensity (based on LST) being up to 14°C higher than corresponding urban–rural differences in Ta.
Variability of Soil Moisture and Sea Surface Temperatures Similarly Important for Warm-Season Land Climate in the Community Earth System Model
Authors: Orth Rene , Seneviratne Sonia I. 
Published: December 2016

Abstract
Both sea surface temperatures (SSTs) and soil moisture (SM) can influence climate over land. This paper presents a comprehensive comparison of SM versus SST impacts on land climate in the warm season. The authors perform fully coupled ensemble experiments with the Community Earth System Model in which they prescribe SM or SSTs to the long-term median seasonal cycles. It is found that SM variability overall impacts warm-season land climate to a similar extent as SST variability, in the midlatitudes, tropics, and subtropics. Removing SM or SST variability impacts land climate means and reduces land climate variability at different time scales by 10%–50% (temperature) and 0%–10% (precipitation). Both SM- and SST-induced changes are strongest for hot temperatures (up to 50%) and for extreme precipitation (up to 20%). These results are qualitatively similar for the present day and the end of the twenty-first century. Removed SM variability affects surface climate through corresponding variations in surface energy fluxes, and this is controlled to first order by the land–atmosphere coupling strength and the natural SM variability. SST-related changes are partly controlled by the relation of local temperature or precipitation with the El Niño–Southern Oscillation. In addition, in specific regions SST-induced SM changes alter the “direct” SST-induced climate changes; on the other hand, SM variability is found to slightly affect SSTs in some regions. Nevertheless a large level of independence is found between SM–climate and SST–climate coupling. This highlights the fact that SM conditions can influence land climate variables independently of any SST effects and that (initial) soil moisture anomalies can provide valuable information in (sub)seasonal weather forecasts.
Impacts of Anthropogenic Heat on Summertime Rainfall in Beijing
Authors: Nie Wanshu , Zaitchik Benjamin F. , Ni Guangheng , Sun Ting 
Published: December 2016

AbstractAnthropogenic heat is an important component of the urban energy budgets that can affect land surface and atmospheric boundary layer processes. Representation of anthropogenic heat in numerical climate modeling systems is therefore important when simulating urban meteorology and climate and has the potential to improve weather forecasts, climate process studies, and energy demand analysis. Here, spatiotemporally dynamic anthropogenic heat data estimated by the Building Effects Parameterization and Building Energy Model (BEP-BEM) are incorporated into the Weather Research and Forecasting (WRF) Model system to investigate its impact on simulation of summertime rainfall in Beijing, China. Simulations of four local rainfall events with and without anthropogenic heat indicate that anthropogenic heat leads to increased rainfall over the urban area. For all four events, anthropogenic heat emission increases sensible heat flux, enhances mixing and turbulent energy transport, lifts PBL height, increases dry static energy, and destabilizes the atmosphere in urban areas through thermal perturbation and strong upward motion during the prestorm period, resulting in enhanced convergence during the major rainfall period. Intensified rainfall leads to greater atmospheric dry-down during the storm and a higher poststorm LCL.
Surface Relative Dispersion in the Southwestern Gulf of Mexico
Authors: Sansón Luis Zavala , Pérez-Brunius Paula , Sheinbaum Julio 
Published: December 2016

AbstractSurface dispersion properties in the southwestern Gulf of Mexico are studied by using a set of 441 drifters released during a 7-yr period and tracked for 2 months on average. The drifters have a drogue below the surface Ekman layer, so they approximately follow oceanic currents. This study follows two different approaches: First, two-particle (or pair) statistics are calculated [relative dispersion and finite-scale Lyapunov exponents (FSLEs)]. Relative dispersion estimates are consistent with theoretical dispersion regimes of two-dimensional turbulence: an exponential growth during the first 3 days, a Richardson-like regime between 3 and 20 days (in which relative dispersion grows as a power law in time), and standard dispersion (linear growth) for longer times. The FSLEs yield a power-law regime for scales between 10 and 150 km but do not detect an exponential regime for short separations (less than 10 km). Robust estimates of diffusivities based on both relative dispersion and FSLEs are provided. Second, two different dispersion scenarios are revealed by drifter trajectories and altimetric data and supported by two-particle statistics: (i) a south-to-north advection of drifters, predominantly along the western shelf of the region, and (ii) a retention of drifters during several weeks at the Bay of Campeche, the southernmost part of the Gulf of Mexico. Dominant processes that control the dispersion are the arrival of anticyclonic Loop Current eddies to the western shelf and their interaction with the semipermanent cyclonic structure in the Bay of Campeche.
Observations of Surface Wave–Current Interaction
Authors: Romero Leonel , Lenain Luc , Melville W. Kendall 
Published: December 2016

AbstractWave–current interaction can result in significant inhomogeneities of the ocean surface wave field, including modulation of the spectrum, wave breaking rates, and wave statistics. This study presents novel airborne observations from two experiments: 1) the High-Resolution Air–Sea Interaction (HiRes) experiment, with measurements across an upwelling jet off the coast of Northern California, and 2) an experiment in the Gulf of Mexico with measurements of waves interacting with the Loop Current and associated eddies. The significant wave height and slope varies by up to 30% because of these interactions at both sites, whereas whitecap coverage varies by more than an order of magnitude. Whitecap coverage is well correlated with spectral moments, negatively correlated with the directional spreading, and positively correlated with the saturation. Surface wave statistics measured in the Gulf of Mexico, including wave crest heights and lengths of crests per unit surface area, show good agreement with second-order nonlinear approximations, except over a focal area. Similarly, distributions of wave heights are generally bounded by the generalized Boccotti distribution, except at focal regions where the wave height distribution reaches the Rayleigh distribution with a maximum wave height of 2.55 times the significant wave height, which is much larger than the standard classification for extreme waves. However, theoretical distributions of spatial statistics that account for second-order nonlinearities approximately bound the observed statistics of extreme wave elevations. The results are discussed in the context of improved models of breaking and related air–sea fluxes.