bluuebunny/crossref_metadata_2025_split huggingface dataset:
Propensity score matched analysis of partial atrioventricular septal defect repair in infancy
Authors: Buratto Edward , Daley Michael , Ye Xin Tao , Radford Dorothy J , Alphonso Nelson , Brizard Christian P , d’Udekem Yves , Konstantinov Igor E 
Published: December 2017

ObjectivePartial atrioventricular septal defect (pAVSD) is usually repaired between 2 and 4 years of age with excellent results. Repair during infancy has been associated with poorer outcomes. However, most infants in reported series had heart failure or significant left atrioventricular valve (LAVV) regurgitation. The impact of surgery during infancy on outcomes remains unclear.MethodsAll children at three institutions who underwent repair of pAVSD from 1975 to 2015 were included. Infants (aged <1 year) were compared with older children in a propensity score matched analysis. Variables used to generate propensity scores were: failure to thrive, congestive heart failure, preoperative LAVV regurgitation, associated congenital heart disease, sex and the presence of trisomy 21.ResultspAVSD repair was performed on 430 children, 17.4% (75/430) were infants. Infants (mean age 0.5±0.3 years) had higher rates of LAVV regurgitation, heart failure and additional cardiac malformations than older children (mean age 4.7±3.5 years). At 30 years, survival for infants was 82.1% (95% CI 70.1% to 89.6%) compared with 95.7% (95% CI 91.3% to 97.9%) in older children (P<0.001).Propensity score matching yielded 52 well-matched pairs. Survival at 30 years was 87.9% (95% CI 75.0% to 94.4%) for infants compared with 98.1% (95% CI 87.1% to 99.7%) for older children (P=0.04). There was no significant difference in freedom from reoperation between the groups.ConclusionsDespite matching for risk factors, survival after repair of pAVSD during infancy is lower than that when repair is performed in older children, with no difference in reoperation rates. This suggests that elective repair of pAVSD should be deferred until after infancy.
Rewriting for sound and complete union, intersection and negation types
Authors: Pearce David J. 
Published: December 2017

Implementing the type system of a programming language is a critical task that is often done in an ad-hoc fashion. Whilst this makes it hard to ensure the system is sound, it also makes it difficult to extend as the language evolves. We are interested in describing type systems using declarative rewrite rules from which an implementation can be automatically generated. Whilst not all type systems are easily expressed in this manner, those involving unions, intersections and negations are well-suited for this.
In this paper, we consider a relatively complex type system involving unions, intersections and negations developed previously. This system was not developed with rewriting in mind, though clear parallels are immediately apparent from the original presentation. For example, the system presented required types be first converted into a variation on Disjunctive Normal Form. We identify that the original system can, for the most part, be reworked to enable a natural expression using declarative rewrite rules. We present an implementation of our rewrite rules in the Whiley Rewrite Language (WyRL), and report performance results compared with a hand-coded solution.
A Haskell compiler for signal transforms
Authors: Mainland Geoffrey , Johnson Jeremy 
Published: December 2017

Building a reusable, auto-tuning code generator from scratch is a challenging problem, requiring many careful design choices. We describe HSpiral, a Haskell compiler for signal transforms that builds on the foundational work of Spiral. Our design leverages many Haskell language features to ensure that our framework is reusable, flexible, and efficient. As well as describing the design of our system, we show how to extend it to support new classes of transforms, including the number-theoretic transform and a variant of the split-radix algorithm that results in reduced operation counts. We also show how to incorporate rewrite rules into our system to reproduce results from previous literature on code generation for the fast Fourier transform.
Although the Spiral project demonstrated significant advances in automatic code generation, it has not been widely used by other researchers. HSpiral is freely available under an MIT-style license, and we are actively working to turn it into a tool to further both our own research goals and to serve as a foundation for other research groups' work in developing new implementations of signal transform algorithms.
Abstract A01: Mechanisms of breast cancer risk in shift workers: Epigenetic changes in the circadian pathway
Authors: Zienolddiny Shan 
Published: December 2017

Abstract
Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm can increase breast cancer risk. Circadian disruption may also affect epigenetic factors such as 5-methyl cytosine methylation in DNA. DNA hypermethylation generally is associated with increased cancer risk, if it occurs in tumor suppressor genes. Some of the circadian genes are known to function as tumor suppressor genes. DNA methylation in cirdavdian genes and its association with breast cancer risk in shiftworkers is little investigated and the limited available data are inconclusive. We here investigated DNA methyalation at 5-meC sites in the promoter regions of core circadian and melatonin receptor genes as a potential mechanism for night work-related breast cancer risk. A nested breast cancer case-control study of nurses working night shifts comprising of seven-hundred breast cancer cases and matched controls was conducted. Methylation at 5-meC sites in a number of core circadian and melatonin receptor genes was in DNA from sputum samples obtained from cases and controls. Changes in methylation status of the 5-meC in DNA (methylation index) and the odds of breast cancer associated with DNA methylation was calculated in relation to the duration and intensity of night shiftwork. We demonstrate that generally the methylation of 5-meC is low for all the genes that were analyzed. However, we will present analyses of the effects of work schedules and duration, as number of consecutive night shifts, on epigenetic changes. The hypothesis is that increased breast cancer risk in workers with long periods of consecutive night shifts may be associated with changes in methylation status of the genes regulation the circadian rhythm.
Citation Format: Shan Zienolddiny. Mechanisms of breast cancer risk in shift workers: Epigenetic changes in the circadian pathway [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A01.
Abstract B08: Differential regulation of Protein Kinase D isoforms in oxidative stress conditions via tyrosine phosphorylation in the activation segment
Authors: Cobbaut Mathias , Derua Rita , Waelkens Etienne , Störz Peter , Janssens Veerle , Lint Johan Van 
Published: December 2017

Abstract
The protein kinase D (PKD) family of kinases belongs to the CAMK group and consists of three highly homologous enzymes. They play a versatile role in cancer cell signaling, primarily downstream of PKC isoforms. Classically PKDs are activated upon co-localization with PKC at DAG containing membranes, where PKC phosphorylates the PKD activation loop, generating active PKD. Besides this, PKDs are also activated in oxidative stress conditions, where PKD1 protects against cellular damage via signaling to NF-kB. While the three isoforms are highly homologous, they are not redundant in their biological function and oncogenic potential. A picture has emerged which associates PKD1 expression and activity with decreased migration and inhibition of epithelial mesenchymal transition (EMT). PKD2 and PKD3 on the other hand are upregulated in various cancers, and show oncogenic potential e.g. via enhanced ECM breakdown and potentiation of angiogenesis. While non-redundant biological roles continue to surface, the biochemical mechanisms behind these discrepant functions remain mostly elusive. Here, we identify an isoform specific regulation of PKD2 in oxidative stress conditions via the phosphorylation of a key Tyrosine residue in the substrate binding loop of the activation segment which is highly conserved in most Ser/Thr kinases. Phosphorylation of this residue selectively occurs in PKD2 (and not in PKD1). While wild-type PKD1 signals to NF-kB in oxidative stress, we could show that wild-type PKD2 signaling to NF-kB is impeded in these conditions. Substitution of the activation segment Tyr-717 in PKD2 with a non-phosphorylatable Phe restores signaling to NF-kB, indicating that Tyr-717 phosphorylation is a key determinant for the signaling outcome of PKDs in oxidative stress.
Note: This abstract was not presented at the conference.
Citation Format: Mathias Cobbaut, Rita Derua, Etienne Waelkens, Peter Störz, Veerle Janssens, Johan Van Lint. Differential regulation of Protein Kinase D isoforms in oxidative stress conditions via tyrosine phosphorylation in the activation segment [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B08.
Abstract B33: The role of WWOX in HNSCC through Wnt/beta-catenin pathway
Authors: Buyru Ayse Nur , Celebi Asuman , Seyhan Betul 
Published: December 2017

Abstract
The second most common fragile site in the human genome is the FRA16D region where the WWOX gene is localized which codes for a 414 amino acid protein. WWOX is a member of the WW-domain containing protein family consisting of 2000 members. It is a partner of several transcription factors and therefore functions in multiple physiological and pathological processes such as cell growth, differentiation and tumor suppression. Genomic alterations within the WWOX gene and its differential expression have been found in a variety of human tumors. Although some transcription factor partners of the WWOX protein have been identified its exact mechanism of action is not known. A recent study indicated that WWOX inhibits the Wnt/β-catenin pathway by preventing the nuclear import of the Dishvelled (Dvl) proteins. Dvl proteins are the main down-stream target of Wnt receptors (Frizzled- FRZ). Following binding of Wnt to its receptor alterations of β-catenin degradation lead to β-catenin accumulation in the cytoplasm. Accumulated β-catenin translocates into the nucleus and activates expression of target genes. Therefore dysregulation of the Wnt signaling pathway is a key oncogenic mechanism in many different cancers. Although Wnt and its receptor FRZ have been analyzed in head and neck squamous cell carcinoma (HNSCC) the intracellular components of the pathway have not been investigated. This is the first study in the literature reporting a role for β-catenin and Dvl mRNA level alterations in HNSCC. In our previous study we have identified that the WWOX gene is inactivated in HNSCC as a result of genetic and epigenetic alterations. To identify the mechanism of action of WWOX in HNSCC in this study we investigated its expression in association with Dvl-1, Dvl-2, Dvl-3 and β-catenin expression in 98 HNSCC samples. We observed down-regulation of the WWOX mRNA in 73.5% of the HNSCC tumor samples compared to their non-cancerous counterparts. Up-regulation of the Dvl-1, Dvl-2, Dvl-3 and β-catenin mRNAs were detected in 32.7%, 36%, 38.8% and 24.5% of the same tumor samples, respectively. We also detected a statistically significant correlation between the WWOX gene expression and mRNA levels of the intracellular components of the Wnt pathway genes. Our results indicate that WWOX acts as a tumor suppressor in the HNSCC development and progression by inhibiting the expression of the Dvl proteins.
Citation Format: Ayse Nur Buyru, Asuman Celebi, Betul Seyhan. The role of WWOX in HNSCC through Wnt/beta-catenin pathway [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B33.
Abstract B36: Contrasting views on the role of mesenchymal stem cells in tumor progression: A systematic review
Authors: Oloyo Ahmed Kolade , Pepper Michael Sean 
Published: December 2017

Abstract
The role of mesenchymal stem cells (MSCs) in the progression of tumor remains controversial. Strong experimental evidences support both inhibitory and stimulatory roles of MSCs on tumor growth. To assess factors responsible for contrasting effects of MSCs on tumor growth, we did a systematic review of existing literature on the effect of MSCs on tumor growth from 01/01/00 - 01/05/16. A total of 168 original research articles with 315 experiments were assessed. Factors considered in the complex relationship between MSCs and tumor growth include: type of experiments (in-vivo, in-vitro), experimental models for the in-vivo studies (syngeneic or xenogeneic), immune status of the experimental animal (competent or deficient), sources and types of cancer and MSCs, status of the MSCs (naïve or engineered), methods of inducing cancer as well as methods of administering the MSCs in vivo and methods used in the in vitro experiments (co-culture or conditioned media). 55% of the studies favor the stimulatory effect of MSCs on tumor growth. The type of experiment is divided almost evenly, as about 53% of all the experiments were conducted in-vitro with 60% of the cancer cells exposed to the MSCs via co-culture methods. 78% of the in-vivo experiments were xenogeneic and 63% of these were carried out in immunocompetent animals. About 80% of both MSCs and cancer cells were sourced from human and 86% of these MSCs were used in their naïve form while 14% were engineered to produce factors that could alter the activity of the MSC itself or that of the cancer cells. About 61% of the MSCs were derived from bone marrow while 15% each were derived from adipose tissues and umbilical cord the remaining 8% MSCs were derived from other various tissues. Tumor growth was inhibited in 86% of experiments that used engineered MSCs. Tumor growth was inhibited in 82% of experiment that used umbilical cord MSCs while tumor growth was promoted in 62% of experiment that employed bone marrow MSCs, but the effect of MSCs on tumor growth was about 57% and 43% stimulatory and inhibitory respectively when adipose tissue derived MSCs were used. Thus several factors determine what effect MSCs would have on the progression of tumor growth.
Note: This abstract was not presented at the conference.
Citation Format: Ahmed Kolade Oloyo, Michael Sean Pepper. Contrasting views on the role of mesenchymal stem cells in tumor progression: A systematic review [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B36.
Abstract IA1: Progress in scaling up cervical cancer prevention in health services of developing countries
Authors: Sankaranarayanan Rengaswamy 
Published: December 2017

Abstract
Cervical cancer is a major threat to women's health accounting for 528,000 new cases and 266,000 deaths annually around 2012, of which 85% occurred in low- and middle-income (LMICs). Substantial declines in cervical cancer incidence and mortality rates can be achieved by integrating HPV vaccination and cervical screening in public health services in LMICs. Since 2007, HPV vaccination has been introduced in national immunization programs in 73 countries, of which 33 are LMICs; in addition it has been introduced in pilot programs in another 17 countries, mostly in sub-Saharan Africa. It is particularly impressive that 7 out of 8 girls have access to HPV vaccination in Latin Region. So far, more than 270 million doses have been administered globally with excellent safety profile and high acceptance, despite the negative publicity surrounding HPV vaccination. The falling vaccine prices, possibility of new vaccines from China and India and the currently recommended two-dose schedule will make HPV vaccination more feasible. Screening is yet to be widely implemented in many LMICs and many of these countries lack the health care infrastructure and resources to introduce efficient screening programs. Screening has been sub-optimally performing in some LMICs for lack of adequate coverage, follow-up and quality assurance. A number of countries have introduced visual inspection (VIA) screening in their health services as opportunistic or pilot programs. HPV testing is the most effective cervical screening tool and HPV negative women are at very low risk for cervical cancer. Currently Mexico and Argentina have introduced HPV screening. The eventual availability of a simple, affordable, faster and accurate HPV tests will facilitate wider HPV screening in LMICs. Planned investments to implement HPV vaccination of single year cohorts of 9-13 year old girls and at least a single HPV screening of women between 30-59 will save many precious lives in developing countries.
Citation Format: Rengaswamy Sankaranarayanan. Progress in scaling up cervical cancer prevention in health services of developing countries [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA1.
Abstract IA14: Targeting human endogenous retroviruses for epigenetic therapy
Authors: Jones Peter A. 
Published: December 2017

Abstract
Vitamin C deficiency is found in patients with cancer and might complicate various therapy paradigms. Here we show how this deficiency may influence the use of DNA methyltransferase inhibitors (DNMTis) for treatment of hematological neoplasias. In vitro, when vitamin C is added at physiological levels to low doses of the DNMTi 5-aza-2'-deoxycytidine (5-aza-CdR), there is a synergistic inhibition of cancer-cell proliferation and increased apoptosis. These effects are associated with enhanced immune signals including increased expression of bidirectionally transcribed endogenous retrovirus (ERV) transcripts, increased cytosolic dsRNA, and activation of an IFN-inducing cellular response. This synergistic effect is likely the result of both passive DNA demethylation by DNMTi and active conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) enzymes at LTR regions of ERVs, because vitamin C acts as a cofactor for TET proteins. In addition, TET2 knockout reduces the synergy between the two compounds. Furthermore, we show that many patients with hematological neoplasia are markedly vitamin C deficient. Thus, our data suggest that correction of vitamin C deficiency in patients with hematological and other cancers may improve responses to epigenetic therapy with DNMTis.
Citation Format: Peter A. Jones. Targeting human endogenous retroviruses for epigenetic therapy [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA14.
Abstract IA17: New ways of targeting Ras
Authors: McCormick Frank 
Published: December 2017

Abstract
Activating K-Ras mutations occur frequently in many cancers, and account for about one million cancer deaths per year worldwide. Currently, no therapies exist that target K-Ras directly, and K-Ras cancers are very difficult to treat. Indeed, they are excluded from treatment with targeted agents such as tarceva and vemurafenib. The K-Ras protein is a member of a large family of related proteins, of which H-Ras and N-Ras are the closest relatives. Ablation of all three Ras genes is likely to be toxic, as these proteins are essential in most signaling transduction pathways. We therefore need to target the mutant oncoprotein itself, or target K-Ras, without affecting H-Ras or N-Ras. The striking similarity of these proteins makes this task challenging, together with the fact that the K-Ras gene expresses two splice variants, K-Ras 4A and K-Ras 4B, each of which can contribute to cancer. Nevertheless, differences do exist between these proteins, and ways in which these can be exploited will be discussed. One approach takes advantage of unique properties of K-Ras 4B, the other targets an amino acid that is shared between K-Ras isoforms, but is not present in H-Ras or N-Ras, or other members of the Ras family. K-Ras processing can be prevented by compounds that block the CAAX box cysteine. We have identified compounds that interact covalently with this cysteine and block prenylation by farnesyl transferase or geranylgeranyl transferase. These compounds reduce expression of K-Ras in cells and have specificity for K-Ras relative to H-Ras and N-Ras and represent another approach to targeting K-Ras specifically. We have also used new biophysical methods to target K-Ras, including second harmonic generation. This method detects small allosteric changes in proteins, and thus allows identification of small molecules that bind to K-Ras at novel allosteric sites. Drug resistance is likely to be a problem with Ras inhibitors, as it is for all types of cancer therapies. We have identified an approach to killing drug resistant cells that appears effective against a wide range of resistance mechanisms. This was achieved by targeting persister cells that survive targeted agents, but have unique properties that make them vulnerable to attack. The implications of this new strategy will be discussed.
Citation Format: Frank McCormick. New ways of targeting Ras [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA17.