bluuebunny/crossref_metadata_2025_split huggingface dataset:
Description of an incidence-based model for Assessing comorbidity patterns in disease natural history
Authors: Kiri Victor A 
Published: July 2016

BackgroundPatients with a chronic disease often suffer from other diseases called comorbidities, which can be important factors in the assessment of risks associated with the disease and its management. However, comorbidities can pose important methodological issues because factors such as time, age, duration and the disease can influence their impact on the risk of interest.MethodsTo identify comorbidities of a chronic disease, it is common practice to construct 2 separate cohorts of patients—a set with the disease and another as a random sample of patients free of the disease—and compare the event rates for each candidate's comorbidity over a specific period between the 2, while accounting for factors which may confound the results. We describe an incidence-based alternative approach that exploits the longitudinal properties of observational databases to track incident event rates along the natural history of the chronic disease. We illustrate it in a retrospective cohort of patients with chronic obstructive pulmonary disease (COPD) aged 50 and above—each patient with COPD was matched with another without COPD on certain confounding factors.ResultsWe obtained 24 079 matched pairs. We found that chronic conditions such as lung cancer, asthma, fracture and osteoporosis were more common in patients with COPD. We also found evidence of time-varying associations.ConclusionsOur findings in COPD suggest that time is an important factor and comorbidity studies which are based on information in a single fixed period (such as first year postdiagnosis of COPD) are more likely to report spurious associations.
Epstein–Barr virus and regulatory T cells in Egyptian paediatric patients with acute B lymphoblastic leukaemia
Authors: Ateyah Mohamed E , Hashem Mona E , Abdelsalam Mohamed 
Published: July 2016

ObjectiveAcute B lymphoblastic leukaemia (B-ALL) is the most common type of childhood malignancy worldwide but little is known of its origin. Recently, many studies showed both a high incidence of Epstein–Barr virus (EBV) infection and high levels of CD4+CD25+Foxp3+(Treg cells) in children with B-ALL. In our study, we investigated the possible relationship between EBV infection and the onset of B-ALL, and its relation to expression of CD4+, CD25high+Foxp3+ T regulatory cells.Subject and methodsWe analysed expression and mean fluorescence intensity (MFI) of Treg cells in peripheral blood of 45 children with B-ALL and in 40 apparently healthy children as a control, using flow cytometry. Serum anti-EBV viral capsid antigen (VCA) IgG, anti-EBV nuclear antigen (EBNA) IgG (for latent infection) and anti-EBV VCA IgM (for acute infection) were investigated using ELISA.ResultsAnalysis of the Treg cells population in patients and controls revealed that expression of CD4+CD25high+T lymphocytes was higher in patients than in controls (mean±SD 15.7±4.1 and 10.61±2.6 in patients and controls, respectively, and MFI of Foxp3 was 30.1±7.1 and 16.7±3.7 in patients and controls, respectively (p<0.001)). There was a high incidence of latent EBV infection in patients (31%) compared with controls (10%) while the incidence of acute infection was 12% in patients and 0% in the control group. To study the role of latent EBV infection in the pathogenesis of acute B-ALL, OR was calculated (OR=4.06, coefficient index 1.2–13.6).ConclusionsThese findings suggest a possible role for Treg cells and EBV in the pathogenesis of B-ALL. Further studies are needed on the possible mechanisms of tumour genesis related to Treg cells and EBV in children with B-ALL.
Sacroplasty procedural extravasation with high viscosity bone cement: comparing the intraoperative long-axis versus short-axis techniques in osteoporotic cadavers
Authors: Miller Jeffrey W , Diani Art , Docsa Steve , Ashton Kristi , Sciamanna Michele 
Published: July 2016

IntroductionPercutaneous sacroplasty involves image-guided injection of bone cement for sacral insufficiency fractures to alleviate pain and facilitate mobility. Correct sacral placement of the cement and the risk of cement extravasation present procedural challenges. This study compares the occurrence, number, location, and surface area of high viscosity radiopaque bone cement extravasation via biplane fluoroscopy with Dyna CT between the fluoroscopically-guided intraoperative long-axis and short-axis sacroplasty techniques in osteoporotic cadavers.MethodsTen osteoporotic cadavers underwent bilateral percutaneous instillation of VertaPlex HV High Viscosity Radiopaque Bone Cement. Long- and short-axis sacroplasty techniques were randomly assigned to zone 1 of the left or right sacral ala of each cadaver. Cement extravasation data were summarized by technique (long-axis vs short-axis) and time period (15-min and 3-hour post-procedure syngo DynaCT scan) in the form of point and CI estimates for the true proportions of cement extravasation.ResultsNo procedural sacral extravasation differences were observed between the long-axis and short-axis sacroplasty techniques. There were no occurrences of intra-procedural or post-procedural cement extravasation at 15 min or 3 hours in association with either the long-axis sacroplasty technique or the short-axis sacroplasty technique.ConclusionsThe long- and short-axis sacroplasty techniques, using high viscosity cement with careful post-procedural positioning, result in no occurrence of cement extravasation in porous osteoporotic cadaver bone.
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism
Authors: Jia Min , Andreassen Trygve , Jensen Lasse , Bathen Tone Frost , Sinha Indranil , Gao Hui , Zhao Chunyan , Haldosen Lars-Arne , Cao Yihai , Girnita Leonard , Moestue Siver Andreas , Dahlman-Wright Karin 
Published: July 2016

AbstractEstrogen receptor α (ERα) is a key regulator of breast growth and breast cancer development. Here, we report how ERα impacts these processes by reprogramming metabolism in malignant breast cells. We employed an integrated approach, combining genome-wide mapping of chromatin-bound ERα with estrogen-induced transcript and metabolic profiling, to demonstrate that ERα reprograms metabolism upon estrogen stimulation, including changes in aerobic glycolysis, nucleotide and amino acid synthesis, and choline (Cho) metabolism. Cho phosphotransferase CHPT1, identified as a direct ERα-regulated gene, was required for estrogen-induced effects on Cho metabolism, including increased phosphatidylcholine synthesis. CHPT1 silencing inhibited anchorage-independent growth and cell proliferation, also suppressing early-stage metastasis of tamoxifen-resistant breast cancer cells in a zebrafish xenograft model. Our results showed that ERα promotes metabolic alterations in breast cancer cells mediated by its target CHPT1, which this study implicates as a candidate therapeutic target. Cancer Res; 76(19); 5634–46. ©2016 AACR.
Oncolytic Adenovirus Expressing Monoclonal Antibody Trastuzumab for Treatment of HER2-Positive Cancer
Authors: Liikanen Ilkka , Tähtinen Siri , Guse Kilian , Gutmann Theresia , Savola Paula , Oksanen Minna , Kanerva Anna , Hemminki Akseli 
Published: July 2016

AbstractMonoclonal anti-HER2 antibody trastuzumab has significantly improved the survival of patients with HER2-overexpressing tumors. Nevertheless, systemic antibody therapy is expensive, limited in efficacy due to physical tumor barriers, and carries the risk of severe side effects such as cardiomyopathy. Oncolytic viruses mediate cancer-selective transgene expression, kill infected cancer cells while mounting antitumor immune responses, and have recently demonstrated promising efficacy in combination treatments. Here, we armed an oncolytic adenovirus with full-length trastuzumab to achieve effective in situ antibody production coupled with progressive oncolytic cancer cell killing. We constructed an infectivity-enhanced serotype 5 oncolytic adenovirus, Ad5/3-Δ24-tras, coding for human trastuzumab antibody heavy- and light-chain genes, connected by an internal ribosome entry site. Infected cancer cells were able to assemble full-length functional antibody, as confirmed by Western blot, ELISA, and antibody-dependent cell-mediated cytotoxicity assay. Importantly, oncolysis was required for release of the antibody into tumors, providing additional spatial selectivity. Ad5/3-Δ24-tras showed potent in vitro cytotoxicity and enhanced antitumor efficacy over oncolytic control virus Ad5/3-Δ24 or commercial trastuzumab in HER2-positive cancer models in vivo (both P &lt; 0.05). Furthermore, Ad5/3-Δ24-tras resulted in significantly higher tumor-to-systemic antibody concentrations (P &lt; 0.001) over conventional delivery. Immunological analyses revealed dendritic cell activation and natural killer cell accumulation in tumor-draining lymph nodes. Thus, Ad5/3-Δ24-tras is an attractive anticancer approach combining oncolytic immunotherapy with local trastuzumab production, resulting in improved in vivo efficacy and immune cell activation in HER2-positive cancer. Moreover, the finding that tumor cells can produce functional antibody as directed by oncolytic virus could lead to many valuable antitumor approaches. Mol Cancer Ther; 15(9); 2259–69. ©2016 AACR.
Abstract 1000: The long non-coding RNA HIF1A-AS2 regulates mesenchymal glioma stem cell tumorigenicity
Authors: Mineo Marco , Ricklefs Franz , Rooj Arun , Lyons Shawn M. , Ivanov Pavel , Chiocca Ennio A. , Godlewski Jakub , Bronisz Agnieszka 
Published: July 2016

Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, which initiation and progression is driven by a subset of self-renewing GBM stem-like cells (GSCs). Long-non coding RNAs (lncRNAs) have been recently shown to play important roles in regulating numerous biological processes both in physiologic and pathologic condition. Identification of functional lncRNAs important for GBM initiation and progression may shed new light on understanding pathophysiology of the disease. We used a custom made lncRNA Nanostring platform to profile the expression of lncRNAs in subtype-characterized collection of patient-derived GSCs. We demonstrated that lncRNA signature may distinguish between GSC subtypes. Out of 73 lncRNAs we found 7 that were overexpressed specifically in the most aggressive mesenchymal (M) GSC subtype. Among them, HIF1A-AS2 was the most differentially expressed lncRNA. HIF1A-AS2 was reported to be overexpressed in many types of cancers; however its biological function and its role in GBM progression are unknown. Knockdown of HIF1A-AS2 in M GSCs resulted in reduced growth, increased cytotoxicity, and it strongly inhibited their neurosphere formation capability. Using more global approach we found out that knockdown of HIF1A-AS2 in M GSCs caused deregulation of several out of 730 cancer-related genes. Functional bioinformatic analysis revealed that these differentially expressed mRNAs are closely related to proliferation, transcriptional regulation and cell division. RNA pull-down assay showed that HIF1A-AS2 may exert its effects through specific binding of RNA helicase DHX9, a multifunctional protein with important roles in transcription, pre-mRNA processing and translation. We also demonstrated that HMGA1, a gene known to be regulated by DHX9, was specifically down-regulated in HIF1A-AS2 knockdown cells both at mRNA and protein level. Finally, we showed that silencing of HIF1A-AS2 blocked M GSC tumor growth in vivo resulting in significant survival benefits. Taken together, our results suggest HIF1A-AS2 as an important lncRNA in pathophysiology of GBM.
Citation Format: Marco Mineo, Franz Ricklefs, Arun Rooj, Shawn M. Lyons, Pavel Ivanov, Ennio A. Chiocca, Jakub Godlewski, Agnieszka Bronisz. The long non-coding RNA HIF1A-AS2 regulates mesenchymal glioma stem cell tumorigenicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1000.
Abstract 1008: Leptin-induced NILCO in endometrial cancer is linked to obesity
Authors: Daley-Brown Danielle , Oprea-Ilies Gabriela , Vann Kiara T. , Pattillo Roland , Lillard James , Gonzalez-Perez Ruben Rene 
Published: July 2016

Abstract
Background: Endometrial cancer (EmCa) Type I is estrogen dependent whereas Type II is estrogen independent and usually associated with endometrial atrophy. Type II is the more aggressive form with a poor prognosis. Obesity is a growing epidemic and is a major risk factor for EmCa. African-American women have higher incidence of obesity, and are more likely to die from EmCa even though the risk of developing EmCa is lower in Caucasian women. Obesity is characterized by high serum leptin levels, which are associated cancer incidence, metastasis and poor prognosis. Leptin's effects in breast cancer are related to the induction of a crosstalk between Notch, IL-1 and leptin (NILCO). It is hypothesize that there is a positive correlation between Type II EmCa, NILCO and obesity.
Methods: The expression of NILCO components was determined by immunohistochemistry in Type I vs Type II EmCa biopsies from obese African American and lean tissue array from Chinese patients. Additionally, the effects of leptin on cell proliferation and NILCO expression were determined in cell lines derived from Type I and Type II EmCa (Ishikawa, Hec1a, An3ca and KLE), respectively.
Results: NILCO components were expressed higher in Type II EmCa, more advanced disease, and correlated with obesity. Also, leptin induction of NILCO was more prominent in Type II EmCa cells.
Conclusions: Obesity signals (i.e., leptin) could induce NILCO in EmCa. Leptin could play a significant role in EmCa progression, especially in Type II EmCa. Therefore, NILCO could represent a novel biomarker for the more aggressive Type II EmCa. These observations could be more relevant for obese EmCa patients.
Citation Format: Danielle Daley-Brown, Gabriela Oprea-Ilies, Kiara T. Vann, Roland Pattillo, James Lillard, Ruben Rene Gonzalez-Perez. Leptin-induced NILCO in endometrial cancer is linked to obesity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1008.
Abstract 1026: PEG-LPrA2 is a non-toxic adjuvant for triple negative breast cancer
Authors: Dill Courtney D. , Harbuzariu Adriana , Rampoldi Antonio , Lipsey Crystal C. , Lanier Viola , Harmon Tia , Daley-Brown Danielle , Tchio Cynthia , Candelaria Pierre , Gonzalez-Perez Ruben Rene 
Published: July 2016

Abstract
Background: Triple Negative Breast Cancer (TNBC) is an aggressive cancer with poor prognosis and is difficult to treat. Current standard therapy for the disease includes a combination of chemotherapeutic drugs: doxorubicin (DOX), paclitaxel (TAX), and cyclophosphamide (CTX). These drugs are ineffective as they exhibit shortcomings and several side effects. TNBC patients develop chemoresistance that may be enhanced by leptin, which affects survival, proliferation, and angiogenesis. Our lab developed and tested a novel and specific inhibitor of leptin signaling, LPrA2. A pegylated derivative of LPrA2 (PEG-LPrA2), with enhanced bioavailability, was successfully used in mouse breast cancer models. Preliminary data showed that PEG-LPrA2 was non-toxic in vitro. Therefore, it is hypothesized that PEG-LPrA2 is not toxic in vivo.
Methods: To determine potential toxicity of PEG-LPrA2, in vitro and in vivo assays were performed. In vitro toxicity of PEG-LPrA2 was tested in a human non-malignant mammary epithelial cell line (MCF-10A). MCF-10A cells were cultured in 96 well plates (5,000 cells/ well) and grown to 70-80% confluence. Cells were treated with PEG-LPrA2 for 24 hrs and viability was determined via MTT assay. In vivo toxicity studies were performed in obese mice. Fifty-seven, eight week old C57BL/6J mice (Charles River Laboratories) were divided into 6 groups. Control mice were fed a low fat diet (10% Kcal from fat) and the rest of the mice were fed a high fat diet (60% Kcal from fat) for 11 weeks. Obesity was characterized as body weight (BW) ≥ 25% BW of control mice. Obese mice were divided into six groups (n = 7/each). Mice were injected with 50 μL of either Sc-PEG-LPrA2 (scramble control) or active inhibitor, PEG-LPrA2, (0.1 mM, 1 mM, or 5 mM) two times a week, for eight weeks. Blood chemistries were analyzed. Additionally, heart, liver, and kidney tissue were harvested and examined to determine toxicity. The tissues were probed for OB-R via immuno histochemistry.
Results: The results showed no changes in BW or food intake. Additionally, no evident changes in blood parameters and organ histology were found.
Conclusions: PEG-LPrA2 is non-toxic and could serve as an adjuvant therapy for standard TNBC chemotherapeutics.
Citation Format: Courtney D. Dill, Adriana Harbuzariu, Antonio Rampoldi, Crystal C. Lipsey, Viola Lanier, Tia Harmon, Danielle Daley-Brown, Cynthia Tchio, Pierre Candelaria, Ruben Rene Gonzalez-Perez. PEG-LPrA2 is a non-toxic adjuvant for triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1026.
Abstract 105: Bioinformatic analysis of RNA-Seq data to search for novel diagnostic/prognostic biomarkers of pancreatic ductal adenocarcinoma
Authors: Sosa Omar J. , Paixão Vinícius F. , Setubal João C. , Reis Eduardo M. 
Published: July 2016

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly human malignancies. The only curative treatment available is the surgical removal of the tumor in early stages of the disease. Current methods for early detection and treatment are poor, justifying more studies in this field. We aim to generate a high-resolution catalog of the PDAC transcriptome, to reveal transcriptional alterations associated with the malignant phenotype of PDAC. To that end 28 patient matched samples of PDAC and nontumor adjacent pancreatic tissue were processed for the production of rRNA subtracted cDNAs libraries and subsequently sequenced in the Illumina HiSeq platform producing 17 million 100 nt paired-end reads per sample on average. We are implementing an informatics pipeline to detect and evaluate the differential expression in PDAC of well-annotated genes, including long noncoding RNAs (lncRNAs). In addition, we will search for novel lncRNAs and alternative splicing isoforms of protein-coding genes expressed in pancreatic tissues. Following the initial quality control (FastQC) and trimming of low quality regions (Trimmomatic), reads from each sample were aligned to the human genome (TopHat2) and a count table with the number of reads per gene for each sample was created (HTSeq). For evidence of changes across experimental conditions we use DESeq2, identifying 310 genes up-regulated and 354 down-regulated (p-adjusted&lt;0.001 and lfc&lt;|3.3|), including 156 lncRNAs. The differentially expressed genes detected are involved in pathways related to cancer, regulation of cell cycle process, membrane and secreted proteins. De novo transcript assembly (Trinity) revealed a number of yet unannotated transcripts and isoforms expressed in pancreatic tissues. Altogether, the transcript catalog generated herein provides a valuable resource for the identification of novel putative candidate biomarkers to improve the early detection or evaluation of therapeutic response in PDAC.
Work supported by FAPESP, CNPq and CAPES.
Citation Format: Omar J. Sosa, Vinícius F. Paixão, João C. Setubal, Eduardo M. Reis. Bioinformatic analysis of RNA-Seq data to search for novel diagnostic/prognostic biomarkers of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 105.
Abstract 106: Transcriptionnal profiling of upper-tumor urothelial carcinomas
Authors: Malouf Gabriel , Mouawad Roger , Su Xiaoping , Yao Hui , Comperat Eva , Roupret Morgan , Spano Jean-Philippe , Khayat David 
Published: July 2016

Abstract
Background: Upper-tumor urothelial carcinomas (UTUC) represent 5% among all urothelial tumors. The most frequent histological variant is transitional cell carcinomas (TCC). UTUC might arise within renal pelvis or ureters. Several studies suggested aggressive behavior of tumors arising within the ureter as compared to those which develop within renal pelvis. However, whether there is a biological basis of this difference remains unknown.
Methods: We performed RNAsequencing on fourteen UTUC including 6 cases arising in the ureter and 8 in renal pelvis. Library prep followed by next-generation sequencing were done using Illumina Hiseq platform. Unsupervised clustering using differentially expressed genes was used to identify cancer subtypes. Identified subtypes were correlated with clinico-pathological features. Pathway analysis was performed using Gene Set Enrichment Analysis (GSEA).
Results: Unsupervised clustering of gene expression revealed two clusters. Surprisingly, all tumors (n = 5/5) encompassing C1 were located in the ureters as compared to only one (n = 1/9) in C2 cluster (p = 0.003). No difference was observed between C1 and C2 clusters according to age, gender, grade, muscle-invasion status and stage. Using stringer cut-off (fold change ≥ or ≤-2 and FDR&lt;0.05), 34 genes were found to be differentially expressed between the 2 clusters. GSEA revealed negative enrichment of several pathways related to B and T-cell activation in C1 relative to C2 cluster. This was the case for NAIVE_TCELL_VS_DC_UP (p = 0.01; FDR = 0.16) and NAIVE_BCELL_VS_NEUTROPHIL_UP (p = 0.002; FDR = 0.12). Among the most overexpressed genes in C1 cluster, we identified the serine/threonine-protein kinase gene SGK2 (Fold change = 17; FDR = 0.004) as a putative therapeutic target. Of note, AIM2 which is part of the inflammasome with a key role in tumorigenic reversion was one of the most down-regulated genes (fold change = -24; FDR = 0.02) in C1 cluster.
Conclusion: Our report suggests that transcriptional profiling of UTUC arising in the ureters and renal pelvis might be distinct. The observed difference might be related to immune response. Validation of these data in a larger independent cohort with analysis of the immune infiltrate is required.
Citation Format: Gabriel Malouf, Roger Mouawad, Xiaoping Su, Hui Yao, Eva Comperat, Morgan Roupret, Jean-Philippe Spano, David Khayat. Transcriptionnal profiling of upper-tumor urothelial carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 106.