bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PL02-01: Childhood cancer: Effects of genetic susceptibility and exposures to environmental agents
Authors: Wiemels Joseph L. 
Published: May 2019

Abstract
Childhood cancers tend to be relatively simple in tumor genetic and epigenetic terms, reflecting their short latency of formation their identity as a misappropriation of normal tissue developmental growth pathways. The relatively few identified genetic susceptibility alleles are concentrated in developmental transcription factors and cell cycle genes, and tumor genetic and epigenetic changes tend to disrupt the same genes as found in genome-wide association studies. We will focus our discussion on the most frequent and the most studied childhood cancer, childhood leukemia, and on these topics: (i) the role of fetal tumor genetic and epigenetic alterations in identification of specific risk factors affecting in time windows of development (ii) the role of immune development and infection in cancer induction, and (iii) the impact of genetic variants that induce susceptibility to subtypes of cancer in specific populations.
The only bona fide causes of childhood leukemia are ionizing radiation and certain genetic predisposition and susceptibility alleles. Current progress in defining unrecognized causal pathways is being made by defining cancer in cytogenetic and epigenetic terms. As an example, chemical carcinogens (cigarette smoke, paints, solvents) are linked to leukemias with t(12;21) TEL-AML1 translocations, which have a prenatal origin. In genetic susceptibility terms, specific alleles (ARID5B, PIP4K2A) are associated leukemia with high hyperdiploidy.
While leukemia has long been linked to exposure to infectious agents, our current understanding implicates an interaction between immune development and response to early infections. We will present data showing that children who contract leukemia may be born with a congenital immune defect causing them to react to infections more strongly, resulting in damage to hematopoietic precursors and increased leukemia risk. Recognition of such immune defects, combined with identification of preleukemic mutations and genetic susceptibility markers, provides a likely roadmap for future efforts at early detection or risk stratification. Such an approach can lead to prevention efforts, which might involve immunologic modifications for risk reduction along with screening for appropriate genetic and epigenetic mutations.
Citation Format: Joseph L. Wiemels. Childhood cancer: Effects of genetic susceptibility and exposures to environmental agents. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PL02-01.
Abstract PL05-04: Tumor biomarker discovery for aspirin chemoprevention by molecular pathological epidemiology (MPE) approach
Authors: Ogino Shuji 
Published: May 2019

Abstract
Regular use of aspirin reduces incidence and mortality of various cancers. Experimental and clinical studies support a carcinogenic role of PTGS2 (cyclooxygenase-2), which is a mediator of inflammation, and a target of aspirin. Recent research using “Molecular Pathological Epidemiology (MPE)” approach (Ogino et al. J Natl Cancer Inst 2010; Chia et al. Nat Rev Clin Oncol 2012; Spitz et al. Cancer Discovery 2012, etc.) has shown that aspirin use is associated with better clinical outcome in PIK3CA-mutated colorectal carcinoma, suggesting somatic PIK3CA mutation as a molecular biomarker that predicts response to aspirin (Liao et al. NEJM 2012). Furthermore, aspirin use appears to decrease risk of BRAF-wild-type colorectal cancer, but not risk of BRAF-mutated subtype (Nishihara et al. JAMA 2013), suggesting that individuals who are susceptible to BRAF-wild-type colorectal cancer may derive benefit from aspirin use. Interestingly, the findings on aspirin use and molecular markers (BRAF and PIK3CA) in relation to cancer incidence and mortality appear to be inconsistent, but this may reflect changes in the tumor microenvironment during progression of neoplasia. Although there are currently not many cohorts that can replicate these intriguing findings, it is increasingly possible to design MPE database worldwide using routine molecular testing data, as molecular pathology testing is becoming routine clinical practice. In order to test chemopreventive effects of a number of anti-inflammatory drugs and their complex interactions, it is essential to build large-scale population-based databases including medication use, lifestyle factors, tumor tissue molecular pathology, and clinical outcome. Such databases can generate novel information on potential chemopreventive benefits of drugs, which can be further tested by experimental models and clinical trials.
Citation Format: Shuji Ogino. Tumor biomarker discovery for aspirin chemoprevention by molecular pathological epidemiology (MPE) approach. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PL05-04.
Abstract PR03: Frizzled 9 expression is a potential marker of response to iloprost chemoprevention of lung cancer
Authors: Tennis Meredith , Nield Lori , Merrick Dan , Keith Robert 
Published: May 2019

Abstract
Lung cancer remains the leading cause of cancer death in the United States and chemoprevention offers an appealing area of investigation in the face of limited therapeutic success. We recently demonstrated improvement in endobronchial histology in former smokers after oral iloprost treatment. Of the 48 patients who received iloprost in the chemoprevention trial, 23 had regressive histology and 25 had stable or progressive histology. Identifying markers that predict response to treatment will refine target populations for future trials and clinical applications. In vitro studies of NSCLC indicate that iloprost, a prostacyclin analogue, acts through the G-protein coupled receptor Frizzled 9 (Fzd9) instead of the prostacyclin receptor. We hypothesize that Fzd9 expression status predicts response to iloprost chemoprevention and that expression is modified by promoter hypermethylation. Patients who have lost Fzd9 expression will not respond to iloprost treatment. If Fzd9 is lost by methylation, a demethylating agent could restore Fzd9 expression and sensitivity to iloprost chemoprevention. In a urethane A/J mouse model of lung cancer, Fzd9 mRNA expression is reduced in lung tumors compared to matched, uninvolved lung tissue. Human lung tumors demonstrated reduced Fzd9 mRNA expression compared to matched normal lung tissue. Fzd9 expression is also decreased in human primary dysplastic cell lines, suggesting that loss of Fzd9 expression occurs early in lung tumorigenesis. Non-transforming lung epithelial cell lines (B2B or HBEC) were treated for four weeks with 1% cigarette smoke condensate. B2B cells were treated with the tobacco carcinogen NNK (10μM) for 2 hours. Both treatment conditions resulted in reduced Fzd9 mRNA expression measured by qPCR. Future work will assess Fzd9 expression in an in vitro chemoprevention and smoking model, in tissues from additional mouse models of lung cancer, and in tissues from chemoprevention trials. These initial studies suggest that Fzd9 expression is lost in early smoking-induced lesions. This study has the potential to improve iloprost lung cancer chemoprevention by allowing future trials to more effectively target high-risk patients and by providing a clinical biomarker for identification of chemoprevention candidates.
This abstract is also presented as Poster A29.
Citation Format: Meredith Tennis, Lori Nield, Dan Merrick, Robert Keith. Frizzled 9 expression is a potential marker of response to iloprost chemoprevention of lung cancer. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR03.
Abstract PR04: Exogenous estrogen as a mediator of racial differences in insulin-like growth factor-I levels among postmenopausal women
Authors: Jung Su Yon , Hays-Grudo Jennifer , Paskett Electra , Hursting Stephen D. , Fenton Jenifer , Pollak Michael , Vitolins Mara , Chang Shine 
Published: May 2019

Abstract
Purpose: The role of exogenous estrogen use in explaining racial/ethnic differences in insulin-like growth factor-I (IGF-I) levels in relation to cancer risk is not clear. We investigated whether the relationship between race and circulating bioactive IGF-I proteins is mediated by exogenous estrogen and the extent to which exogenous estrogen explained the race–IGF-I relationship in postmenopausal women.
Methods: This cross-sectional study included 636 white and 133 black postmenopausal women enrolled in an ancillary study of the Women's Health Initiative Observational Study between February 1995 and July 1998. The race–IGF-I relationship was analyzed using ordinal regression, and quartiles of molar ratios of IGF-I/IGF binding protein-3 were used as a proxy of bioactive IGF-I outcomes. To assess exogenous estrogen as a mediator of the race–IGF-I relationship, we used the Baron-Kenny method and an estimation of the proportional change in the odds ratios for race on IGF-I levels plus a bootstrapping test for the significance of the mediation effect.
Results: Compared with white women, black women were more likely to have high IGF-I levels and less likely to use exogenous estrogen. After accounting for race, estrogen nonusers had higher IGF-I levels than estrogen users did. When women were stratified by oral contraceptive (OC) ever use, among OC ever users, exogenous estrogen showed a strong mediation effect (67%; P=0.018) in the race–IGF-I relationship. Moreover, when women were classified by a history of hypertension, the IGF-I levels of women with a history of hypertension were higher than those of women with no history of hypertension. Of the women with a history of hypertension, exogenous estrogen explained differences in IGF-I levels between white and black women to a modest degree (23%; P=0.029).
Conclusions: Exogenous estrogen use has a potentially important role in racial/ethnic disparities in cancer risk among postmenopausal women.
This abstract is also presented as Poster A38.
Citation Format: Su Yon Jung, Jennifer Hays-Grudo, Electra Paskett, Stephen D. Hursting, Jenifer Fenton, Michael Pollak, Mara Vitolins, Shine Chang. Exogenous estrogen as a mediator of racial differences in insulin-like growth factor-I levels among postmenopausal women. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR04.
Abstract PR07: Body size and multiple myeloma mortality: A pooled analysis of 20 prospective studies
Authors: Teras Lauren R. , Kitahara Cari M. , Birmann Brenda M. , Hartge Patricia A. , Wang Sophia S. , Patel Alpa V. , Robien Kim , Adami Hans-Olov , Weiderpass Elisabete , Giles Graham G. , Gapstur Susan M. , González Amy Berrington de , Purdue Mark 
Published: May 2019

Abstract
Multiple myeloma is a rare but highly fatal hematologic malignancy. Excess weight may be associated with this cancer, but several unresolved questions remain regarding timing and location of body weight in relation to multiple myeloma risk. To better understand these relationships, we conducted a pooled analysis of multiple myeloma mortality using 1.5 million participants from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Among cohort participants, the median baseline body mass index (BMI) was 25.6 and 21.0 kg/m2 at cohort entry and early adulthood, respectively, and the median waist circumference at cohort entry was 88 cm. During follow-up (10 years on average), we documented 1,388 multiple myeloma deaths. Using proportional hazards regression we calculated pooled hazard ratios (HRs) and 95% confidence intervals (CIs) overall and by sex. We observed associations with elevated multiple myeloma mortality for higher BMI at cohort entry (HR 1.09, 95% CI: 1.03-1.16 per 5kg/m2), early-adult BMI (HR=1.12, 95% CI: 0.97-1.30 per 5kg/m2), and waist circumference at cohort entry (HR= 1.06, 95% CI: 1.02-1.10 per 5cm) for men and women combined. These results were slightly stronger for women but the differences were not statistically significant. Mutual adjustment for each of the body size measures yielded similar results. Individuals who were the heaviest both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) had the greatest risk of myeloma mortality compared to those with BMI 18.5-&lt;25 at both time points (HR=1.71, 95% CI: 1.18-2.49). Waist-to-hip ratio and height were not significantly associated with multiple myeloma mortality. These observations suggest that both overall and central obesity play a role in myeloma mortality, and that maintaining a higher body weight throughout adulthood confers the highest risk of death from this cancer.
This abstract is also presented as Poster B47.
Citation Format: Lauren R. Teras, Cari M. Kitahara, Brenda M. Birmann, Patricia A. Hartge, Sophia S. Wang, Alpa V. Patel, Kim Robien, Hans-Olov Adami, Elisabete Weiderpass, Graham G. Giles, Susan M. Gapstur, Amy Berrington de González, Mark Purdue, on behalf of the Cohort Consortium Pooling Project on BMI and Mortality. Body size and multiple myeloma mortality: A pooled analysis of 20 prospective studies. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr PR07.
Abstract SS02-01: Nature and epidemiology of e-cigarettes
Authors: Leischow Scott J. 
Published: May 2019

Abstract
Electronic nicotine delivery systems (ENDS, or e-cigarettes) are devices that deliver nicotine in a way that mimics to some extent the look and feel of tobacco cigarettes, but do not include any tobacco. They were created by an engineer in China, and typically include a battery, heating element, nicotine, medium for carrying nicotine molecules into the mouth once heated (eg propylene glycol) and sometimes flavoring. In the US, a court case declared that ENDS products should be considered ‘tobacco’ from a regulatory perspective, and they will eventually be regulated by the US FDA under its authority to regulate tobacco products. In the meantime, they are being sold extensively in convenience stores and the internet, and social media has increased awareness and use of the products. Sales of e-cigarettes have become a multi-billion dollar industry, and financial analysts anticipate that sales will continue to expand depending on regulatory decisions.
E-cigarettes are controversial for several reasons. They are used in much the same way as a cigarette (puffed), and the user exhales a vapor that looks like smoke. Thus, some in public health are concerned that they could become a ‘gateway’ to use of tobacco cigarettes. Moreover, there is concern that youth will begin using the products given the easy access to them, become addicted, and perhaps eventually switch to tobacco cigarettes. However, even though some studies have found toxic substances in some brands of e-cigarettes, use by both and adults continues to increase dramatically. Several studies have suggested that most adults use e-cigarettes to help them to quit smoking, so there is both promise and risk from these unique nicotine delivery systems.
In this presentation, an overview of how e-cigarettes work will be presented, and surveillance data (including on social media) will be presented that demonstrates the rapid increase in use that has occurred in the US. This presentation will provide a primer on e-cigarettes to serve as a background for the papers and discussion that will come after it.
Citation Format: Scott J. Leischow. Nature and epidemiology of e-cigarettes. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr SS02-01.
Congenital Heart Disease and Risk of Cardiovascular Disease: A Meta‐Analysis of Cohort Studies
Authors: Wang Tingting , Chen Lizhang , Yang Tubao , Huang Peng , Wang Lesan , Zhao Lijuan , Zhang Senmao , Ye Ziwei , Chen Letao , Zheng Zan , Qin Jiabi 
Published: May 2019

Background

Despite remarkable success in the surgical and medical management of congenital heart disease (
CHD
), some survivors still experience cardiovascular complications over the long term. The goal of this study was to evaluate the association between
CHD
and risk of cardiovascular disease (
CVD
) by conducting a meta‐analysis of cohort studies.

Methods and Results

A systematic literature search of several databases was conducted through April 2018 to identify studies reporting the risk of
CVD
, stroke, heart failure, and coronary artery heart disease in
CHD
survivors. The quality of individual studies was assessed using the Newcastle‐Ottawa scale. The overall risk estimates were pooled using fixed‐effects meta‐analysis. Subgroup analyses were performed to explore possible sources of heterogeneity. Nine cohort studies comprising 684 200 participants were included. The overall combined relative risks for people with
CHD
compared with the controls were 3.12 (95%
CI,
3.01–3.24) for
CVD
, 2.46 (95%
CI,
2.30–2.63) for stroke, 5.89 (95%
CI,
5.58–6.21) for heart failure, and 1.50 (95%
CI,
1.40–1.61) for coronary artery heart disease. Significant heterogeneity was detected across studies regarding these risk estimates. Heterogeneity in the risk estimate of
CVD
was explained by geographic region, type of study design, sample source, age composition, and controlled confounders.

Conclusions

This meta‐analysis of cohort studies of
CHD
found an association of increased risk of
CVD
in later life, although we cannot determine whether this association is confounded by a risk factor profile of
CVD
among
CHD
survivors or whether
CHD
is an independent risk factor.
Fondaparinux Sodium Compared With Low‐Molecular‐Weight Heparins for Perioperative Surgical Thromboprophylaxis: A Systematic Review and Meta‐analysis
Authors: Kumar Arun , Talwar Ashna , Farley Joel F. , Muzumdar Jagannath , Schommer Jon C. , Balkrishnan Rajesh , Wu Wenchen 
Published: May 2019

Background

Fondaparinux sodium has been compared with low‐molecular‐weight heparins (
LMWH
) in randomized controlled trials for perioperative surgical thromboprophylaxis. However, the results from these studies are inconsistent in terms of efficacy and safety to reach a clinical decision. The objective of this study was to systematically review the randomized controlled trials comparing the efficacy and safety of fondaparinux and
LMWH
for perioperative surgical thromboprophylaxis.

Methods and Results

Systematic search in various databases was done to identify randomized controlled trials comparing fondaparinux and
LMWH
published during the years 2000 to 2017. Outcomes of interest in this study included venous thromboembolism up to day 15, all‐cause mortality up to day 90, major bleeding, and minor bleeding during the treatment period. Analyses were performed with the relative odds based on a random‐effects model using Mantel‐Haenszel statistics. Results were presented as odds ratios with their 95% CIs. The assessment of study quality was performed as per Cochrane collaboration. After screening 10 644 articles, 12 randomized controlled trials including 14 906 patients were included in the final analyses. Pooled analyses showed the odds of venous thromboembolism in the fondaparinux group were 0.49 times the odds in
LMWH
group (
OR
=0.49 [0.38–0.64]). However, the odds of major bleeding in the fondaparinux group were 1.48 times the odds in the
LMWH
group (
OR
=1.48 [1.15–1.90]).

Conclusions
Fondaparinux was associated with a superior efficacy in terms of reduction of venous thromboembolism in this meta‐analysis. However, it was also associated with increased odds of major bleeding.
Determining Etiology of Facial Nerve Paralysis With MRI: Challenges in Malignancy Detection
Authors: Tolisano Anthony M. , Hunter Jacob B. , Sakai Mark , Kutz Joe Walter , Moore William , Pinho Marco , Isaacson Brandon 
Published: May 2019

Objective: Compare experts’ ability to differentiate malignant and benign causes of facial nerve paralysis (FNP) using the initial presenting magnetic resonance image (MRI) for each patient. Methods: This retrospective case-controlled study compared MRIs for 9 patients with a malignant cause for FNP, 8 patients with Bell’s palsy, and 9 cochlear implant patients serving as controls. The initial presenting MRI for each condition was used such that raters were evaluating real-world rather than optimal studies. Three blinded expert raters independently evaluated each segment of the facial nerve for abnormalities, provided a diagnosis, and graded MRI quality. Cohen’s and Light’s kappa were used to calculate interrater reliability and overall index of agreement, respectively. Results: MRI protocols for the malignancy group were universally suboptimal. There was poor agreement among raters for abnormalities of the facial nerve along the brainstem (0.13), geniculate (0.10), tympanic segment (0.12), and mastoid segment (0.13); moderate agreement along the cisternal segment (0.58) and internal auditory canal (0.55); and fair agreement along the labyrinthine segment (0.26) and extratemporal segment (0.36). Agreement regarding final diagnosis was fair (0.37) when compared to the true diagnosis. There were 2 false negative interpretations (failure to correctly identify malignancy) and 1 false positive interpretation. Conclusion: MRI for FNP is often initially performed with an incorrect protocol and thus may fail to reliably differentiate neoplastic from inflammatory FNP even when interpreted by experienced clinicians. Nevertheless, expert readers correctly diagnosed 87.5% of malignant causes of FNP despite these limitations.
On the Normative Elements of Marxism
Authors: Jain Satish K. 
Published: May 2019

This article is concerned with the normative structure underlying the Marxist doctrine and its logical consistency. Two of the most fundamental elements of Marxism are historical materialism and the idea of justice underlying an exploitation-free society. It is argued in the paper that these two elements do not cohere with each other; and that the construction of an interpretation that would make the normative structure underlying Marxism logically consistent poses intractable difficulties. JEL: B51