tbuckley/cabot-search huggingface dataset:
A new mathematical formulation to integrate supply and demand within a choice-based optimization framework
Authors: Meritxell Pacheco, Shadi Sharif Azadeh, Michel Bierlaire
Journal: Eurosurveillance (2016)

Discrete choice models are the state-of-the-art for the mathematical modeling of demand. Based on the concept of random utility, they are able to predict the choice behavior of individuals. However, these models are highly non linear and non convex in the variables of interest, and therefore difficult to be included in mixed linear optimization models. Furthermore, these models are of great importance in transportation revenue management systems. In this research, we propose a new mathematical modeling framework to include general random utility assumption inside discrete optimization framework. In order to tackle the non-linearity and non-convexity imposed by choice-models, we rely on simulation to capture the probabilistic nature of demand. Since the formulation has been designed to be linear, the price to pay is the high dimensionality of the problem. We propose an alternative formulation aiming at reducing the size of the problem. We have performed some preliminary experiments for small instances in order to compare the performances of the two models. Note that regardless from the implemented formulation, additional techniques such as decomposition methods may be required for more general instances.
Abstract 742: A novel multidrug metronomic chemotherapy significantly delays tumor growth in mice
Authors: Maria Tagliamonte, Annacarmen Petrizzo, Maria Lina Tornesello, Antonio Luciano, Domenica Rea, Antonio Barbieri, Claudio Arra, Maria Napolitano, Gennaro Ciliberto, Franco M. Buonaguro, Luigi Buonaguro
Journal: Cancer Research (2016)

Abstract The tumor immunosuppressive microenvironment represents a major obstacle to an effective tumor-specific cellular immune response. We have previously shown that a novel multi-drug chemotherapy administered in a metronomic fashion was able to increase immune response to peptides. The chemotherapy consisted of a cocktail including taxanes (paclitaxel and docetaxel) and alkylating (cyclophosphamide) agents. The newly designed strategy was shown to be safe, well tolerated and significantly efficacious (Tagliamonte et al., CII 2015). In the present study, the effect on the immunosuppressive tumor microenvironment by the same multi-drug cocktail was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. Treated animals showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such an effect was directly correlated with CD4+ T cell reduction and CD8+ T cell increase. A significant reduction in the percentage of both CD25+FoxP3+ and CD25+CD127low regulatory T cell population was found in the spleens as well as in the tumor lesions. An intrinsic CD8+ T cell response specific to B16 naturally expressed Trp2 TAA was observed. The same metronomic chemotherapy combined to a vaccine based on mutated antigens, was subsequently shown to increase immune response to vaccine resulting in a significant delay of B16 tumor growth as well as animal survival. The novel multi-drug daily metronomic chemotherapy evaluated in the present study was very effective in counterbalancing the immunosuppressive tumor microenvironment and enhancing vaccine efficacy. Consequently, the intrinsic as well as vaccine-induced anti-tumor T cell immunity could exert its function containing tumor growth. Overall, the described metronomic chemotherapy may represent a promising adjuvant approach to enhance anti-tumor cellular immunity and amplify the biological effects of therapeutic cancer vaccines. Citation Format: Maria Tagliamonte, Annacarmen Petrizzo, Maria Lina Tornesello, Antonio Luciano, Domenica Rea, Antonio Barbieri, Claudio Arra, Maria Napolitano, Gennaro Ciliberto, Franco M. Buonaguro, Luigi Buonaguro. A novel multidrug metronomic chemotherapy significantly delays tumor growth in mice. [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 742.
Melanoma inhibitory activity (MIA) reflects chondrocyte anabolism in chronic inflammatory arthritis: Suppression by pro-inflammatory cytokines is reversed by targeted therapy
Authors: B. Vandooren, M. Van Lierop, T. Cantaert, L. De Rycke, E. Kruithof, E. M. Veys, F. De Keyser, E. Bos, A. Boots, D. Baeten
Journal: Annals of the Rheumatic Diseases (2006)
Abstract 1710: Novel syngeneic mouse gastric cancer models identified Sca-1 as a gastric cancer stem cell marker
Authors: Jun Won Park, Hark K. Kim
Journal: Cancer Research (2016)

Abstract Genetically well-defined syngeneic mouse models for gastric cancer are not available in the scientific community, but critical for the development of immunotherapeutic agents. We generated primary mouse gastric cancer cell line NCC-S1 (S1) established from a Villin-cre;Smad4F/F;Trp53F/F;Cdh1F/wt mouse and its metastatic variant cell line NCC-S1M (S1M). These cells closely recapitulated human diffuse type gastric cancers in histology and molecular profiles. S1M cells showed enhanced in vivo growth and metastatic potentials compared with S1 cells, and developed orthotopic and heterotopic tumors in immunocompetent mice in predictable manner. S1M allograft model was useful for testing the efficacy of an immunotherapeutic agent, anti-4-1BB. Sca-1 was overexpressed in S1M cells compared with S1 cells. Approximately 7% of gastric cancer cells in primary tumors expressed Sca-1. Sca-1high cells were more tumorigenic according to the in vivo limiting dilution assay, and more resistant to cisplatin and fluorouracil. Sca-1high cells overexpressed CD133, CD44, EPCAM and Bcl-xL. A chromatin immunoprecipitation analysis demonstrated that Sca-1 was a β-catenin/LEF1 target gene. Expression profiles of 85 genes overexpressed in Sca-1high S1 cells clustered 123 pretreatment gastric cancer patient samples according to the overall survival following cisplatin/fluorouracil chemotherapy. Thus, our novel metastatic gastric cancer cell lines are useful resources for drug development, and identified Sca-1 as a novel gastric cancer stem cell marker that mediates β-catenin signaling. Citation Format: Jun Won Park, Hark K. Kim. Novel syngeneic mouse gastric cancer models identified Sca-1 as a gastric cancer stem cell marker. [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 1710.
Well-differentiated grade 3 digestive neuroendocrine tumors: Myth or reality? The PRONET study group.
Authors: Jean-Yves Scoazec, Anne Couvelard, Genevieve Monges, Emmanuelle Leteurtre, Genevieve Belleannee, Serge Guyetant, Pierre Duvillard, Marie Danjoux, Xavier Parot, Come Lepage
Journal: Journal of Clinical Oncology (2012)

4129 Background: In contrast to the 2000 World Health Organization (WHO) classification of digestive neuroendocrine tumors (NET) in which morphologic differentiation was the first criterion, the 2010 WHO classification of NET is based mostly on histologic grade. NET are now classified into three main categories: NET G1 (mitotic count &lt;2/10 HPF and/or ≤2% Ki67 index), NET G2 (2-20/10 HPF and/or 3-20%), and neuroendocrine carcinoma (NEC) of small or large cell type. While NET G1 and G2 are well-differentiated tumors, NEC are considered poorly differentiated G3 tumors. We looked at the agreement between grade and differentiation to determine whether all NET can be readily classified according to the 2010 WHO classification. Methods: We designed a 1-year prospective, epidemiologic study to assess the characteristics of newly diagnosed NET, including diagnostic pathology. From August 2010 to July 2011, all pathology laboratories in France were invited to register all incident cases of gastroenteropancreatic (GEP) and thoracic NET, excluding small cell carcinoma. For GEP-NET, investigators were asked to indicate morphologic differentiation (according to WHO 2000) and elements of histologic grade (mitotic index, Ki67 index), according to ENETS. Results: Of 500 invited centers, 80 participated; 1417 incidental cases were included and 77 excluded (duplicates or exclusion criteria), totaling 1340 cases; 778 (58.1%) were GEP-NET; 660/778 (85%) were well differentiated, 72 (9%) poorly differentiated, and 46 (6%) adenocarcinoid, nonclassified, or not evaluable; 422 (54.2%) were G1, 220 (28%) G2, 104 (13.5%) G3, and 32 (4.1%) had missing grades. Of those deemed G3, 72 (69%) were described as poorly differentiated, 21 (20%) as well differentiated (mean Ki67 index 35%, range 25%-60%), and 11 (10.5%) as adenocarcinoid. Conclusions: In this prospective, epidemiologic study, overall agreement between grade and differentiation was good. However, a significant proportion of G3 NET were classified as well differentiated and thus unclassifiable by 2010 WHO classification. This group of tumor deserves to be included in future classifications to help the clinician decide whether they should be treated as NET G1/G2 or NEC G3.
Alternatives in Animal Testing
Authors: Isabelle Fabre
Journal: Environmental Health Perspectives (1996)

The use of alternative methods to animal testing are an integral part of the 3Rs concept (refine, reduce, replace) defined by Russel & Burch in 1959. These approaches include in silico methods (databases and computer models), in vitro physicochemical analysis, biological methods using bacteria or isolated cells, reconstructed enzyme systems, and reconstructed tissues. Emerging "omic" methods used in integrated approaches further help to reduce animal use, while stem cells offer promising approaches to toxicologic and pathophysiologic studies, along with organotypic cultures and bio-artificial organs. Only a few alternative methods can so far be used in stand-alone tests as substitutes for animal testing. The best way to use these methods is to integrate them in tiered testing strategies (ITS), in which animals are only used as a last resort.
RETRACTED: Role of HCP5-miR-139-RUNX1 Feedback Loop in Regulating Malignant Behavior of Glioma Cells
Authors: Hao Teng, Ping Wang, Yixue Xue, Xiaobai Liu, Jun Ma, Heng Cai, Zhuo Xi, Zhen Li, Yunhui Liu
Journal: Molecular Therapy (2016)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the editors. Molecular Therapy is retracting this article. After investigating concerns of image duplication raised by a reader, the editors identified evidence for image manipulation in altered fashion in Figures 3B, 6B, and 8B. This reuse (and in part misrepresentation) of data without appropriate attribution represents a severe abuse of the scientific publishing system. The authors have not agreed to retract the paper and maintain that the issues identified did not affect the major conclusions of the article. Retraction Notice to: Role of HCP5-miR-139-RUNX1 Feedback Loop in Regulating Malignant Behavior of Glioma CellsTeng et al.Molecular TherapyMay 23, 2022In Brief(Molecular Therapy 24, 1806–1822; October 2016) Full-Text PDF
Abstract 2286: Targeting the notch pathway: A potential therapeutic approach for desmoid tumors
Authors: Danielle Braggio, Hui Shang, Ya-Jung Lee, Ghadah A. Al-Sannaa, Chad J. Creighton, Svetlana Bolshakov, Alexander JF Lazar, Dina Lev, Raphael E. Pollock
Journal: Cancer Research (2016)

Abstract Desmoid tumors (DTs) are rare mesenchymal lesions that can recur repeatedly. When it is feasible, DTs are surgically resected; however, this often results in high recurrence rates. Recently, treatment with PF-03084014, a potent γ-secretase inhibitor, has been shown to have antitumor activity in several tumor types by affecting the WNT/β-catenin pathway. Consequently, Notch pathway inhibition by PF-03084014 might be a promising approach for DT treatment. The expression of Notch pathway components was analyzed in DT tissues and cell strains with immunohistochemistry and Western blotting, respectively. A panel of DT cell strains was exposed to PF-03084014 and evaluated for cell proliferation. Antitumor effects were assessed via cell cycle, apoptosis, and migration and invasion analysis. Cells treated with PF-03084014 were characterized with a gene array analysis combined with Ingenuity Pathway Analysis. The results showed that Notch pathway components were expressed at different levels in DTs. Hes1 (Hes Family BHLH Transcription Factor 1) was overexpressed in DT tumors versus dermal scar tissue, and PF-03084014 caused significant decreases in Notch intracellular domain and Hes1 expression in DT cell strains. PF-03084014 decreased DT cell migration and invasion and also caused cell growth inhibition in DT cell strains, most likely through cell cycle arrest. Gene array analysis combined with Ingenuity Pathway Analysis showed that Wnt1-inducible signaling pathway protein 2 possibly regulated Notch and WNT pathways after treatment with PF-03084014 through integrin. Our findings suggest that the Notch pathway is an important DT therapeutic target. Furthermore, PF-03084014 has significant antitumor activity against DTs, and it may be an alternative strategy for DT treatment. Citation Format: Danielle Braggio, Hui Shang, Ya-Jung Lee, Ghadah A. Al-Sannaa, Chad J. Creighton, Svetlana Bolshakov, Alexander JF Lazar, Dina Lev, Raphael E. Pollock. Targeting the notch pathway: A potential therapeutic approach for desmoid tumors. [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 2286.
Dasatinib (SPRYCEL®) 50mg or 70mg BID Versus 100mg or 140mg QD in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Resistant or Intolerant to Imatinib: Results of the CA180-034 Study.
Authors: Andreas Hochhaus, D.W. Kim, P. Rousselot, P.E. Dorlhiac-Llacer, J. Milone, S. Francis, E. Bleickardt, H. Kantarjian
Journal: Blood (2006)
Survival disparities in pediatric skin cancer: Analysis of population-based Florida cancer registry (1981-2009).
Authors: Erin Dunn, Kevin Joseph Moore, Feng Miao, Tulay Koru-Sengul
Journal: Journal of Clinical Oncology (2015)

e21033 Background: Pediatric melanoma is increasing in incidence, and differences in incidence rates between children and adolescents exist. We identified disparities in pediatric skin cancer survival in the Floridian population across sociodemographic groupings such as race, ethnicity, neighborhood poverty status (NPS), skin cancer type, and age. Methods: The Florida Cancer Data System (1981-2009) was linked with US census to explore median survival and 1-, 3-, 5-year survival rates by sociodemographics for pediatric population (0-9, 10-19). Survival was compared by gender, race, ethnicity, and NPS. Survival was modeled with multivariate Cox regression to calculate hazard ratio (HR) and 95% confidence interval (95%CI). Overall survival is calculated by the elapsed time from skin cancer diagnosis to death or last contact for living patients. Results: Of the 471 patients diagnosed with pediatric skin cancer, 60% had malignant melanoma (MM) and 17% had UV-related skin cancer. The majority was female (54%), White (92%), middle-high/highest NPS (63%), living in urban setting (96%) and had private insurance (48%). Overall 1-,3-,5-year survival rates were 94.3%, 76.4%, and 61.4%, respectively. Overall median survival was 6.2 yrs (95%CI:4.4-9.3) and varied between Blacks (17.2) and Whites (6.1), Hispanics (2.4), and non-Hispanics (6.2) and highest (13.0), middle-high (5.8), and middle-low (5.8) NPS. MM patients had longer median survival (7.9;5.8-13.0) compared to UV-related skin cancer (3.9;1.4-4.4). Children aged 0-9 had the shortest median survival (2.4;1.5-2.4) compared to aged 10-19 (7.7;5.3-9.4). UV-related cancer patients had worse survival compared to MM (HR = [2.5]; 95%CI:1.3-5.0). Those aged 10-19 had better survival than those aged 0-9 ([0.3];0.1-0.9). Conclusions: Multiple studies have found skin cancer to be on the rise in the pediatric population. It is important to elucidate variation in survival associated with different sociodemographic factors to identify groups with the greatest burden. Revealing differences in skin cancer survival across race, ethnicity, NPS, type, and age is important in the design and creation of pediatric skin cancer interventions.
The Outcome Of Allogeneic Hematopoietic Cell Transplantation In Children With FLT3/ITD-Positive Acute Myelogenous Leukemia
Authors: Tal Schechter, Adam Gassas, Heidi Chen, Jessica A. Pollard, Soheil Meshinchi, Zaidman Irina, Johann K. Hitzler, Mohamed M. Abdelhaleem, Richard H. Ho, Jennifer Domm, Ann E. Woolfrey, Haydar A Frangoul
Journal: Blood (2013)
The obstructive sleep apnoea syndrome in adolescents
Authors: Carole L Marcus, Brendan T Keenan, Jingtao Huang, Haibo Yuan, Swaroop Pinto, Ruth M Bradford, Christopher Kim, Sheila Bagchi, Francois-Louis Comyn, Stephen Wang, Ignacio E Tapia, Greg Maislin, Christopher M Cielo, Joel Traylor, Drew A Torigian, Richard J Schwab
Journal: Thorax (2016)

<h3>Background</h3> The obstructive sleep apnoea syndrome (OSAS) results from a combination of structural and neuromotor factors; however, the relative contributions of these factors have not been studied during the important developmental phase of adolescence. We hypothesised that adenotonsillar volume (ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway electromyographic response to subatmospheric pressure and the ventilatory response to CO<sub>2</sub> during sleep would be major predictors of OSAS risk. <h3>Methods</h3> 42 obese adolescents with OSAS and 37 weight-matched controls underwent upper airway MRI, measurements of Pcrit, genioglossal electromyography and ventilatory response to CO<sub>2</sub> during wakefulness and sleep. <h3>Results</h3> ATV, NPAV, activated and hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO<sub>2</sub> during sleep were all associated with OSAS risk. Multivariate models adjusted for age, gender, body mass index and race indicated that ATV, NPAV and activated Pcrit each independently affected apnoea risk in adolescents; genioglossal electromyography was independently associated in a reduced sample. There was significant interaction between NPAV and activated Pcrit (p=0.021), with activated Pcrit more strongly associated with OSAS in adolescents with larger NPAVs and NPAV more strongly associated with OSAS in adolescents with more negative activated closing pressure. <h3>Conclusions</h3> OSAS in adolescents is mediated by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated Pcrit). This may have important implications for the management of OSAS in adolescents.
Endoscopic submucosal dissection for curative resection of a superficial rectal lesion over a varix in a patient with cirrhosis
Authors: José Rodrigues, Pedro Barreiro, Rita Herculano, Liliana Carvalho, Susana Marques, Cristina Chagas
Journal: Endoscopy (2015)

A 70-year-old woman with a history of congestive heart failure and alcoholic liver disease was referred to our unit because of intermittent hematochezia. Colonoscopy was performed and showed multiple rectal varices. In addition, in the distal rectum, a 30-mm laterally spreading tumor of granular type could be seen with a central nodular component over a varix ([Fig. 1]). Following multidisciplinary evaluation, endoscopic submucosal dissection (ESD) was planned.
Abstract 2714: Inhibition of human telomerase by new purine analogs
Authors: Wilnelly M. Hernandez-Sanchez, Diane Baus, Anthony J. Berdis, Derek J. Taylor
Journal: Cancer Research (2016)

Abstract Telomeres are the end caps of linear chromosomes that help to ensure genomic stability. Because of the inability of DNA polymerases to synthesize the extreme ends of the lagging strand, telomeres get slightly shorter each time a cell divides. When telomeres get extremely short, a state of senescence is triggered which halts cell division. Some cells that require an extended lifespan (e.g. embryonic cells, germ lines and stem cells) use an enzyme called telomerase to maintain telomeres at a length that is sufficient to escape senescence. Whereas telomerase is undetectable, in adult somatic tissue, it is upregulated in 85-90% of all metastatic tumors; enabling cancer cells to divide indefinitely. Due to this unique property of cancer cells, targeting telomerase is a viable chemotherapeutic approach. Nucleotide analogs have been shown to inhibit telomerase activity (e.g. azidothymidine or AZT), albeit modestly, to promote telomere shortening in cancer cell lines. Also, most of these nucleotide analogs are limited by requirement of high dosage (e.g. The IC50 of AZT varies from 0.25 to 1.35 mM). Therefore, while promising, there is a need to develop other nucleotide analogs that are more potent in inhibiting telomerase activity. We have screened a series of new purines analogs using a direct in vitro telomerase assay. These nucleotide analogs were developed to have different chemical modifications around the indole group of the nucleobase. We have identified two purine analogs (5-MeCITP and 6-NITP) that inhibit telomerase activity in vitro. 5-MeCITP was measured to have an inhibition constant (ki) of ∼45μM, which is significantly efficient. Future efforts will include evaluation of the lead nucleoside analogs in telomerase positive cancer cell lines to determine their effect on telomere length and cell survival. Citation Format: Wilnelly M. Hernandez-Sanchez, Diane Baus, Anthony J. Berdis, Derek J. Taylor. Inhibition of human telomerase by new purine analogs. [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 2714.