bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA12: Intra- and intertumoral heterogeneity and response to therapy in mouse models of SCLC
Authors: Lim Jing Shan , Yang Dian , Shue Yan Ting , Winslow Monte , Sage Julien 
Published: May 2018

Abstract
Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma that accounts for ~15% of all lung cancers and causes over 200,000 deaths worldwide each year. The majority of SCLC patients have metastatic disease at the time of diagnosis; for these patients, the median survival, even with treatment, is 7-12 months, and the 5-year overall survival is &lt;1%. SCLC is managed with first-line chemotherapy–often cisplatin or carboplatin with etoposide. However, the majority of SCLC patients suffer relapse within months of completing initial therapy due to the persistence of a subpopulation of chemotherapy-resistant cells. Treatment options for SCLC have remained virtually unchanged for the past 30 years, and there are no approved targeted therapies in SCLC.
To dissect the molecular changes that regulate SCLC progression, it is critical to analyze purified SCLC cells from tumors at known stages of tumorigenesis. This has not been possible previously using either mouse models or human specimens due to the 1) limited access to lung cancers at defined stages of malignant progression, 2) inability to unambiguously isolate SCLC cells away from stromal cells, and 3) difficulty in performing genome-wide analyses on the few cells that can be isolated from metastases in mouse models or patient biopsies. To overcome these obstacles, we have developed mouse models of SCLC including Cre/lox-mediated deletion of key tumor suppressors (p53, Rb, and the Rb family member p130) as well as activation of fluorescent reporters. This triple-knockout (TKO) model recapitulates the genetics, histology, and metastatic ability of human SCLC.
Using this mouse model, we have recently identified new levels of intratumoral heterogeneity in SCLC tumors, including the presence of tumor-propagating cells (TPCs) as well as Notch-active non-neuroendocrine tumor cell population that promotes the growth of TPCs in a non-cell autonomous but tumor-intrinsic manner. Using TKO mice, we have also uncovered distinct mechanisms of intertumoral heterogeneity during tumor progression; in particular, we have shown that one group of tumors gains metastatic potential by upregulation of the Nfib transcription factor and extensive changes in their chromatin state, while others become metastatic in absence of Nfib-driven chromatin dynamics. These observations will be discussed in the context of how SCLC tumors respond to chemotherapy and candidate targeted therapies.
Citation Format: Jing Shan Lim, Dian Yang, Yan Ting Shue, Monte Winslow, Julien Sage. Intra- and intertumoral heterogeneity and response to therapy in mouse models of SCLC [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA12.
Abstract IA13: Imaging stem cell signals in cancer heterogeneity and therapy resistance
Authors: Reya Tannishtha 
Published: May 2018

Abstract
Our research focuses on the signals that control stem cell self-renewal and how these signals are hijacked in cancer. Using a series of genetic models, we have studied how classic developmental signaling pathways such as Wnt, Hedgehog, and Notch play key roles in hematopoietic stem cell growth and regeneration and are dysregulated during leukemia development. In addition, using real-time imaging strategies we have found that hematopoietic stem cells have the capacity to undergo both symmetric and asymmetric division, and that shifts in the balance between these modes of division are subverted by oncogenes. Further, regulators of this process, including the cell fate determinant Musashi, are critical players in driving progression of solid and liquid cancers and could serve as targets for diagnostics and therapy. Ongoing work is focused on understanding the mechanisms that drive therapy resistance after drug delivery, as well as developing high-resolution in vivo imaging approaches to map normal stem cell behavior and interactions within living animals, and to define how these change during cancer formation.
Citation Format: Tannishtha Reya. Imaging stem cell signals in cancer heterogeneity and therapy resistance [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr IA13.
Abstract PR05: Lineage specifiers SOX2 and NKX2-1 inversely regulate lung tumor immune microenvironment
Authors: Mollaoglu Gurkan , Jones Alex , Mukhopadhyay Anandaroop , Gertz Jason , Jones Kevin , Snyder Eric , Oliver Trudy G. 
Published: May 2018

Abstract
The tumor microenvironment is a critical effector of therapeutic response to diverse stimuli including immunotherapies. Lineage-specific drivers of cancer are known to dictate tumor differentiation and response to therapy, but how they influence the tumor immune microenvironment is largely unknown. SOX2 and NKX2-1 are critical regulators of lung development and cancer, with SOX2 amplifications associated with squamous lung cancer and NKX2-1 amplifications associated with lung adenocarcinoma. Here we employ and develop new genetically engineered mouse models (GEMMs) of lung cancer to interrogate the impact of SOX2 and NKX2-1 on innate immune infiltration. Squamous and adenocarcinoma GEMMs accurately recapitulate features of their human counterparts, including an enrichment of tumor-associated neutrophils (TANs) specifically in squamous lung cancer. We show that SOX2 recruits TANs, whereas NKX2-1 suppresses TANs, in the absence of histopathologic changes. SOX2 and NKX2-1 inversely regulate the neutrophil chemoattractant, Cxcl5, which is also upregulated in human squamous lung tumors. Using a novel GEMM of squamous lung cancer with a rapid latency of 3-4 months, preliminary data suggest that neutrophils can regulate adeno- to squamous transdifferentiation in vivo. Together these data reveal how lineage specifiers influence the tumor immune microenvironment, which in turn may regulate cancer cell fate.
This abstract is also being presented as Poster B19.
Citation Format: Gurkan Mollaoglu, Alex Jones, Anandaroop Mukhopadhyay, Jason Gertz, Kevin Jones, Eric Snyder, Trudy G. Oliver. Lineage specifiers SOX2 and NKX2-1 inversely regulate lung tumor immune microenvironment [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr PR05.
Predicting the Presence of Oral Squamous Cell Carcinoma Using Commonly Dysregulated MicroRNA in Oral Swirls
Authors: Yap Tami , Koo Kendrick , Cheng Lesley , Vella Laura J. , Hill Andrew F. , Reynolds Eric , Nastri Alf , Cirillo Nicola , Seers Christine , McCullough Michael 
Published: May 2018

Abstract
Oral swirls are a noninvasive, rapidly collected source of salivary microRNA (miRNA) potentially useful in the early detection of disease states, particularly oral squamous cell carcinoma (OSCC). The aim of this study was to predict the presence of OSCC using a panel of OSCC-related dysregulated miRNA found in oral swirls, identified jointly in data from formalin-fixed paraffin-embedded (FFPE) and fresh-frozen specimens. Next-generation sequencing (NGS) was used to determine miRNA fold changes in FFPE OSCC specimens relative to histologically normal epithelium. These data were placed with NGS of fresh-frozen tissue data of The Cancer Genome Atlas database to select a panel of commonly dysregulated miRNA. This panel was then analyzed by RT-qPCR in RNA extracted from oral swirls collected from 30 patients with OSCC and 30 controls. Upregulation of miR-31 and miR-21 and downregulation of miR-99a, let-7c, miR-125b, and miR-100 were found between OSCC and controls in both FFPE and fresh-frozen samples. These miRNAs were studied in a training set of 15 OSCC versus 15 control oral swirls to develop a dysregulation score [AUC, 0.95; 95% confidence interval (CI), 0.88–1.03] and classification tree. A test cohort of 15 OSCC versus 15 control oral swirls yielded a dysregulation score AUC of 0.86 (95% CI, 0.79–1.00) with the classification tree identifying 100% (15/15) of OSCC and 67% (10/15) of controls. This study debuts the use of OSCC-associated miRNA, commonly dysregulated in both FFPE and frozen specimens, in oral swirls to indicate the presence of OSCC with high accuracy. Cancer Prev Res; 11(8); 491–502. ©2018 AACR.
Absence of Complications after Endoscopic Mucosal Biopsy
Authors: Johnson Brian , Basson Marc D. 
Published: May 2018

<b><i>Background:</i></b> There is no clarity with regard to the occurrence of serious complications from EGD-driven mucosal biopsy. This is important for considering both clinically indicated procedures and mucosal sampling for research. <b><i>Methods:</i></b> We sought to quantify rates of serious complications from esophagogastroduodenoscopy (EGD) with biopsy. We studied 13,233 patients undergoing outpatient EGD with biopsy over 5 years in 2 North Dakota community hospitals, based on the reasoning that serious complications would cause hospitalization within 30 days. We reviewed the records of all patients with a diagnostic or procedure code or admission within 30 days after the outpatient EGD with biopsy. <b><i>Results:</i></b> Of the 13,233 patients who underwent outpatient EGD with biopsy, 411 were admitted within 30 days, most of them because of their underlying diagnosis. Two patients were admitted due to complications that resulted because of additional simultaneous procedures. No patient was admitted because of complications that could be ascribed to conscious sedation, upper GI endoscopic access, or mucosal biopsy. <b><i>Conclusions:</i></b> These data confirm that EGD biopsy is safe within community settings and suggest that the risk/benefit ratio for performing EGD biopsy for research is likely to be favorable if the research has scientific merit. Serious complications or perforation following EGD biopsy did not occur in 13,233 patients in community hospitals in North Dakota.
An Examination of an Inland-Penetrating Atmospheric River Flood Event under Potential Future Thermodynamic Conditions
Authors: Mahoney Kelly , Swales Dustin , Mueller Michael J. , Alexander Michael , Abel Mimi R. , Malloy Kelsey 
Published: May 2018

AbstractAtmospheric rivers (ARs) are well-known producers of precipitation along the U.S. West Coast. Depending on their intensity, orientation, and location of landfall, some ARs penetrate inland and cause heavy rainfall and flooding hundreds of miles from the coast. Climate change is projected to potentially alter a variety of AR characteristics and impacts. This study examines potential future changes in moisture transport and precipitation intensity, type, and distribution for a high-impact landfalling AR event in the U.S. Pacific Northwest using an ensemble of high-resolution numerical simulations produced under projected future thermodynamic changes.Results indicate increased total precipitation in all future simulations, although there is considerable model spread in both domain-averaged and localized inland precipitation totals. Notable precipitation enhancements across inland locations such as Idaho’s Sawtooth Mountain Range are present in four out of six future simulations. The most marked inland precipitation increases are shown to occur by way of stronger and deeper moisture transport that more effectively crosses Oregon’s Coastal and Cascade mountain ranges, essentially “spilling over” into the Snake River Valley and fueling orographic precipitation in the Sawtooth Mountains. Moisture transport enhancements are shown to have both thermodynamic and dynamic contributions, with both enhanced absolute environmental moisture and localized lower- and midlevel dynamics contributing to amplified inland moisture penetration. Precipitation that fell as snow in the present-day simulation becomes rain in the future simulations for many mid- and high-elevation locations, suggesting potential for enhanced flood risk for these regions in future climate instances of similar events.
Microphysical Properties and Radar Polarimetric Features within a Warm Front
Authors: Keppas S. Ch. , Crosier J. , Choularton T. W. , Bower K. N. 
Published: May 2018

Abstract
On 21 January 2009, the warm front of an extensive low pressure system affected U.K. weather. In this work, macroscopic and microphysical characteristics of this warm front are investigated using in situ (optical array probes, temperatures sensors, and radiosondes) and S-band polarimetric radar data from the Aerosol Properties, Processes and Influences on the Earth’s Climate–Clouds project. The warm front was associated with a warm conveyor belt, a zone of wind speeds of up to 26 m s−1, which played a key role in the formation of extensive mixed-phase cloud mass by ascending significant liquid water (LWC; ~0.22 g m−3) at a level ~3 km and creating an ideal environment at temperatures ~ −5°C for ice multiplication. Then, “generating cells,” which formed in the unstable and sheared layer above the warm conveyor belt, influenced the structure of the stratiform cloud layer, dividing it into two types of elongated and slanted ice fall streaks: one depicted by large ZDR values and the other by large ZH values. The different polarimetric characteristics of these ice fall streaks reveal their different microphysical properties, such as the ice habit, concentration, and size. We investigate their evolution, which was affected by the warm conveyor belt, and their impact on the surface precipitation.
Reciprocal Predictive Accuracy of Sinonasal Symptom Severity, Nasal Endoscopy, and Frequency of Past Chronic Rhinosinusitis Exacerbations
Authors: Speth Marlene M. , Gaudin Robert A. , Hoehle Lloyd P. , Phillips Katie M. , Caradonna David S. , Gray Stacey T. , Sedaghat Ahmad R. 
Published: May 2018

ObjectiveWe sought to determine whether chronic rhinosinusitis (CRS) symptom severity, endoscopic exam findings, and acute exacerbation of CRS (AECRS) frequency—all important and distinct clinical manifestations of CRS—would be predictive of each other and, therefore, inform when further assessment of each other metric should be pursued.Study DesignCross‐sectional cohort study.SettingTertiary academic rhinology clinic.Subjects and MethodsIn total, 241 patients with CRS were prospectively recruited and completed the 22‐item Sinonasal Outcome Test (SNOT‐22) to reflect CRS symptom severity. AECRS frequency was assessed using the number of sinus infections as well as CRS‐related antibiotics and CRS‐related oral corticosteroids used in the past 3 months. An endoscopy score was calculated for each patient.ResultsSNOT‐22 score and AECRS were predictive of each other while AECRS and endoscopy score were not predictive of each other. SNOT‐22 score could be used to predict having had, in the past 3 months, at least 1 sinus infection (area under the curve [AUC] = 0.727; P <. 001), at least 1 CRS‐related antibiotic used (AUC = 0.691; P <. 001), or at least 1 CRS‐related oral corticosteroid course used (AUC = 0.655; P <. 001). Having a SNOT‐22 score ≥30 could be predicted by reporting at least 1 sinus infection (AUC = 0.634; P <. 001), CRS‐related antibiotics (AUC = 0.614; P <. 001), or CRS‐related oral corticosteroids (AUC = 0.616; P <. 001) in the past 3 months. These relationships held for patients with and without nasal polyps.ConclusionThe predictive power of CRS outcome measures reflecting symptomatology, AECRS frequency, and endoscopic findings may be of clinical utility in situations where time or resources are limited to perform an ideally full assessment of patients with CRS.
Betwixt and Between Well and Sick in Cervical Precancer: Canadian Women’s Experiences of Recurring HPV Infections and HPV Vaccination
Authors: Wyndham-West Michelle , Durand Nancy , Santoro Aimee 
Published: May 2018

BackgroundThis research fuses the experiences of a precancer diagnosis with the decision-making surrounding a vaccine that can protect against human papillomavirus strains that women may not have been exposed to. The interviewee cohort is of note as half the women were in their 30s and 40s and 75% were over the age of 26. These groupings are often overlooked in media discourses and narrative research surrounding human papillomavirus and the human papillomavirus vaccine.PurposeWomens’ diagnoses and treatment experiences, including colposcopies, biopsies, and Loop Electrosurgical Excision Procedures, are chronicled to highlight a liminal, precancerous state—one in which they are not deemed healthy, but nor have they been diagnosed with cancer. These are emotion-filled experiences that are ridden with anxiety and fear, but also ones that are structured with self-care strategies to contain human papillomavirus infections and the risk of cervical cancer.MethodsTwenty women who attended Sunnybrook Health Sciences Centre’s human papillomavirus vaccination clinic were interviewed and their narratives were documented and analyzed to determine their experiences surrounding human papillomavirus infections and precancer as well as their motivations for human papillomavirus vaccination.ResultsThe decision to undergo human papillomavirus vaccination was a self-care strategy that accompanied treatment procedures and was a means to reduce cervical cancer risk. While encouraged with the human papillomavirus vaccine’s potential to curb cervical cancer, they had a tempered view of the vaccine and its effectiveness in their cases, given their medical histories.ConclusionsThe research provides an in-depth accounting of an often overlooked grouping in human papillomavirus and human papillomavirus vaccination research and media discourse which, generally, focuses upon middle-school-aged girls and university-/college-aged women. In addition, the research provides recommendations for practice for cervical precancer diagnoses going forward.
A Pilot Study of a Culturally Grounded Breastfeeding Intervention for Pregnant, Low-Income African American Women
Authors: Reno Rebecca 
Published: May 2018

Background: Increasing breastfeeding rates among low-income African American women may work toward the achievement of health equity. The dynamic breastfeeding assessment process (D-BAP) is a community-grounded, equity-focused intervention designed to increase prenatal breastfeeding self-efficacy. Research aim: The aims of the pilot study were (a) to determine the effect of the D-BAP on breastfeeding self-efficacy among pregnant, low-income African American women, (b) to examine the findings among women with no previous breastfeeding experience, and (c) to compare the findings between women with prior breastfeeding experience and those without it. Methods: A pre/post, paired-samples design was utilized. Convenience sampling was used to recruit pregnant, low-income African American women ( N = 25). Participants completed the Breastfeeding Self-Efficacy Scale–Short Form prior to and following the D-BAP. Results: The Wilcoxon signed rank test indicated that participation in the D-BAP had a statistically significant influence on breastfeeding self-efficacy ( z = −2.01, p = .04). Among a subsample of participants with no previous breastfeeding experience ( n = 12), completion of the D-BAP resulted in a statistically significant increase in breastfeeding self-efficacy ( z = −2.36, p = .02). There was no statistically significant difference between those with prior breastfeeding experience and those without it. Conclusion: Breastfeeding among low-income African American women is a health equity issue for which culturally responsive, effective breastfeeding interventions are needed. This research demonstrates an association between completion of the D-BAP and an increase in prenatal breastfeeding self-efficacy.
Histological predictors of renal outcome in lupus nephritis: the importance of tubulointerstitial lesions and scoring of glomerular lesions
Authors: Obrișcă B , Jurubiță R , Andronesi A , Sorohan B , Achim C , Bobeica R , Gherghiceanu M , Mandache E , Ismail G 
Published: May 2018

Introduction Lupus nephritis (LN) affects nearly 60% of patients with systemic lupus erythematosus and up to 30% of them will progress to end-stage renal disease (ESRD), despite receiving aggressive immunosuppressive therapy. The prognostic value of ISN/RPS classification is controversial. Therefore, we aimed to identify clinical and pathological predictors of outcome in LN patients independent of this classification. Material and methods Thirty-seven patients with LN who underwent percutaneous kidney biopsy between 1997 and 2016 were included in this study. Twenty clinical and twenty histological variables were tested for their association with a composite end-point of doubling of serum creatinine, ESRD and death. Univariate and multivariate Cox proportional hazard regression analysis were performed to identify independent predictors of outcome. Results During a median follow-up period of 48 months (IQR: 17.5–120 months), 21.6% of patients reached the composite end-point. The overall survival rate of our cohort was 89% at one year, 86% at five years, 74% at 10 years and 64% at 20 years. Patients with Class IV LN showed the worst prognosis with 44% survival at 10 years, while those who additionally showed crescents and global sclerosis on kidney biopsy had an even lower survival of 21% and 0% at 10 years, respectively. After multivariate adjustment, we identified estimated glomerular filtration rate at baseline (HR, 0.91 per ml/min /1.73 m2; 95% CI, 0.84 to 0.99), 24-hour proteinuria at baseline (HR, 2.04 per g/d; 95% CI, 1.19 to 3.5), crescents (HR, 1.068 per %; 95% CI, 1.003 to 1.091), global sclerosis (HR, 1.036 per %; 95% CI, 0.984 to 1.091), presence of adhesions (HR, 9.2; 95% CI, 1.38 to 61.2) and tubulitis (HR, 13.1; 95% CI; 1.3 to 131) as independent predictors of outcome in our cohort of LN. Conclusions Our study identified glomerular (crescents, global sclerosis, adhesions) and tubulointerstitial (tubulitis) lesions, in addition to clinical variables (renal function, 24-hour proteinuria), as important predictors of renal outcome, independent of the ISN/RPS classification. We suggest that the ISN/RPS classification could be improved by a quantitative assessment of glomeruli with active and chronic lesions and by a greater emphasis given to tubulointerstitial lesions.