tbuckley/cabot-search huggingface dataset:
PTH-028 Gastro-intestinal symptoms in candidates for bariatric surgery
Authors: K Alexandropoulou, H F Medina Lucena, M Reddy, A Wan, A Poullis, J Kang
Journal: Gut (2010)

<h3>Introduction</h3> Obesity and related medical conditions are an increasing problem in the West. British National Institute of Clinical Excellence guidelines recommend the use of bariatric surgery for morbidly obese patients with a body mass index (BMI) of 40 kg/m<sup>2</sup> or more, and for patients with a BMI 35–40 kg/m<sup>2</sup> who have complicating comorbidity that may be improved by weight loss. The prevalence of gastro- oesophageal reflux disease, Barrett9s oesophagus and oesophageal adenocarcinoma is increased in obese individuals. Obesity is also related to psychosocial morbidity and psychological problems which in turn predispose to functional gastrointestinal complaints. We investigated the prevalence of gastro-intestinal symptoms in candidates for bariatric surgery at the time of their pre-operative assessment and 3 months post bariatric surgery. <h3>Methods</h3> Bariatric surgery candidates were asked to complete a locally validated Rome II questionnaire and the Hospital Anxiety and Depression Scale (HAD) at the time of their pre-assessment. The same questionnaires were sent out by post to these patients 3 months after surgery. Their weight and any changes in medication were also recorded at that stage. Pearson9s χ<sup>2</sup> test and Fisher9s exact tests (SPSS V.16) were used for statistical analysis. <h3>Results</h3> Thirty-nine of 58 patients approached pre-operatively completed the study. There were 33 women and 6 men, mean age of 45 years (range 25–60). Thirty five patients (90%) underwent laparoscopic roux-en-Y gastric bypass, RYGB, (30F/5M), three (8%) had a sleeve gastrectomy (2F:1M) and one had intragastric balloon insertion (1F). Mean time of follow-up was 3.4 months. Thirty-eight patients who lost weight (mean 24.5 kg) were included in this analysis. Their mean BMI was 47 kg/m<sup>2</sup> preoperatively and 38.3 kg/m<sup>2</sup> on follow-up. There was a significant reduction in the frequency of heartburn, reported by 11 patients pre-op and only two post-operatively, p&lt;0.05 (RR 5.5, 95% CI 1.3 to 23.2). Post-operatively, significantly more patients reported dysphagia, dyspepsia and vomiting (p&lt;0.05). There was no difference pre and post operatively in frequency of IBS, constipation, diarrhoea, biliary or anorectal disorders. HAD scores for anxiety were similarly unchanged. Although the frequency of depression was reduced by half (from 10.5% to 5.3%) the difference did not reach statistical significance. <h3>Conclusion</h3> The frequency of heartburn was reduced post bariatric surgery. Dysphagia, dyspepsia and vomiting increased in the first 3 months post-operatively.
Herpesvirus-Associated Central Nervous System Diseases After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Qifa Liu, Meiqing Wu, Fen Huang, Zhiping Fan, Hongsheng Zhou, Qianli Jiang, Yu Zhang, Ke Zhao, Li Xuan, Xiao Zhai, Fuhua Zhang, Changxin Yin, Jing Sun, Ru Feng
Journal: Blood (2012)
Abstract LB-047: Single-cell genomics reveals the genesis of cancer: copy number variation precedes single nucleotide variation
Authors: Sunney Xie, Lei Huang, Fei Ma, Jingran Wang, Shigang Ding, Fang Gu, Wenjing Wang, Jing Zhang
Journal: Cancer Research (2015)

Abstract Recent advances in single cell whole genome amplification methods, such as MALBAC [1], have allowed accurate determination of copy number variation (CNV) as well as single nucleotide variation (SNV) of a single cancer cell [2]. In a bulk tissue sample at an early stage of cancer development, detection of abnormal CNV is often difficult, especially when the number of cells with abnormal CNV is small. Single cell genomic analysis is essential in evaluating the relation, if any, between CNV and SNV. We have carried out for the first time single cell genomic analyses of colonoscopy biopsy at different adenoma stages. Some single cells in the Stage II adenoma have CNVs in the tumor suppresser gene APC (the copy number loss reduced from two to one) as well as SNVs in numerous cancer related genes. Interestingly, we found that while some single cells exhibited CNV reduction in APC without SNVs, all single cells with SNVs in COSMIC genes showed the CNV reduction in APC. Moreover we did not see a single cell that has SNVs but not CNVs in an adenoma. These data indicates that the CNV of APC precedes the SNVs in colon cancer development. Furthermore, we found that the single cells from the same adenoma exhibited CNV patterns reproducible among all the cells, indicating that these cells were derived from the same stem cell, in which CNVs resulted from double strand breaks that could not be repaired perfectly. Thus, we have established for the first time a correlation between SNVs and CNVs and propose that SNVs are generated as a consequence of abnormal CNVs in the genome. Therefore, our results could have a significant implication on the genesis of cancer. References (1) Zong, et al. Science 338: 1622-1626 (2012). (2) Ni et al. PNAS 110, 21083 (2013). Note: This abstract was not presented at the meeting. Citation Format: Sunney Xie, Lei Huang, Fei Ma, Jingran Wang, Shigang Ding, Fang Gu, Wenjing Wang, Jing Zhang. Single-cell genomics reveals the genesis of cancer: copy number variation precedes single nucleotide variation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-047. doi:10.1158/1538-7445.AM2015-LB-047
90Y Ibritumomab Tiuxetan (Y2B8, Zevalin®) Radioimmunotherap (RIT) Is Highly Effective for Relapsed or Refractory Indolent B-Cell Non-Hodgkin’s Lymphoma (B-NHL) Pretreated with Rituximab-Containing Chemotherapy (R-Chemo): Japanese Multicenter Phase II Study.
Authors: Michinori Ogura, Yasuo Morishima, Takashi Watanabe, Tomomitsu Hotta, Kennichi Ishizawa, Kuniaki Itoh, Shinichiro Okamoto, Masafumi Taniwaki, Kengo Endo, Kensei Tobinai
Journal: Blood (2006)
Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis
Authors: Xavier Montalban, Stephen L Hauser, Ludwig Kappos, Douglas L Arnold, Amit Bar-Or, Giancarlo Comi, Jérôme de Seze, Gavin Giovannoni, Hans-Peter Hartung, Bernhard Hemmer, Fred Lublin, Kottil W Rammohan, Krzysztof Selmaj, Anthony Traboulsee, Annette Sauter, Donna Masterman, Paulo Fontoura, Shibeshih Belachew, Hideki Garren, Nicole Mairon, Peter Chin, Jerry S Wolinsky
Journal: New England Journal of Medicine (2016)

An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease.In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis.The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain-volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36-Item Short-Form Health Survey. Infusion-related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections.Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long-term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann-La Roche; ORATORIO ClinicalTrials.gov number, NCT01194570 .).
Abstract 841: SNP-FEMS: a method to identify DNA binding proteins interacting with enhancer elements
Authors: Gustavo A. Mendoza-Fandino, Nicholas Woods, Rebekah Baskin, Anxhela Gjyshi, Alvaro N. Monteiro
Journal: Cancer Research (2015)

Abstract An important goal of human genetics is to understand the etiology of genetic traits. In the past few years, genome-wide association studies (GWAS) have identified thousands of chromosomal loci associated with hundreds of traits. GWAS provide a list of variants (single nucleotide polymorphisms, SNP) that are statistically associated with a phenotype, but do not offer any direct evidence about the biological mechanism. Most GWAS cancer susceptibility loci are located in non-coding regions suggesting that they function by modifying tracsriptional regulatory elements, such as enhancers and promoters of target genes. Thus, methods to help identify transcription factors that interact with regulatory regions containing risk associated variants can reveal biological mechanisms. We developed a method, SNP-FEMS (FPLC, EMSA, Mass Spec) that combines liquid chromatography (FPLC), electrophoretic mobility shift assays (EMSAs), and mass spectrometry to identify transcription factors interacting with putative regulatory regions at the 8q24 ovarian cancer risk locus. Human embryonic kidney 293FT nuclear extract was subjected to Sepharose 6 10/300 GL size fractionation and all the fractions were screened for allele-specific binding proteins by EMSA using a probe containing a genome-wide significant SNP. Fractions with positive signal were combined, concentrated and further fractionated with an ion exchange column MonoQ 5/10 GL to further reduce the complexity of the fractions. Fractions were screened by EMSA with the same probe, and the positive fractions were combined, concentrated, subjected to PAGE, in-gel trypsin digestion, and analyzed by Mass Spectrometry to identify proteins in the fractions. Bioinformatics analysis predicted different transcription factors binding to the putative regulatory region and the only transcription factor that was also present in our experimental dataset was the Cyclin AMP-dependent transcription factor ATF-1. This data suggests that ATF1 is implicated in ovarian cancer susceptibility and demonstrate the utility of the SNP-FEMS method to identify regulatory factors involved in ovarian cancer risk. This technique is applicable to any predisposition loci mediated by changes in regulatory elements. Citation Format: Gustavo A. Mendoza-Fandino, Nicholas Woods, Rebekah Baskin, Anxhela Gjyshi, Alvaro N. Monteiro. SNP-FEMS: a method to identify DNA binding proteins interacting with enhancer elements. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 841. doi:10.1158/1538-7445.AM2015-841
Diagnosing liver fibrosis: a narrative review of current literature for dermatologists
Authors: J.R. Potts, C.M. Maybury, A. Salam, J.N. Barker, K. Agarwal, C.H. Smith
Journal: British Journal of Dermatology (2016)

Chronic liver disease is a growing problem worldwide due to obesity, alcohol-related liver disease and viral hepatitis. Liver fibrosis is generally asymptomatic and patients may not present until they have advanced cirrhosis, when the scope for reversibility is limited. Identification of asymptomatic individuals at an early stage is fundamental to reversing the rising toll of liver-related morbidity and mortality. Awareness of liver disease and the techniques for diagnosis is important for dermatologists, not only due to the burden of disease in the general population but also because some dermatology cohorts may have an elevated risk. For example, there is an increased prevalence of metabolic syndrome and excess alcohol use in those with psoriasis and hidradenitis suppurativa. In isolation, standard liver function tests lack sensitivity to detect advanced fibrosis and cirrhosis and are of limited value. Traditionally diagnosis has relied on liver biopsy, which remains the gold standard but is both costly and invasive. There have been several recent advances in the development of noninvasive alternatives. These include scoring systems combining clinical and conventional laboratory parameters for use as screening tools, direct serum biomarkers of fibrogenesis and tissue elastography using both ultrasound (Fibroscan) and magnetic resonance. This review summarizes current and future noninvasive diagnostic techniques for evaluation of liver fibrosis.
Gene Expression Profiling Distinguishes Essential Thrombocythemia from Polycythemia Vera Patients and Identifies a Common Expressed Set of Genes in Relation to JAK2V617F Status
Authors: Eulalia Puigdecanet, Blanca Espinet, Juan Jose Lozano, Lauro Sumoy, Beatriz Bellosillo, Miquel Granell, Alberto Alvarez-Larrán, Leonor Arenillas, Francesc Sole, Sergi Serrano, Francisco Cervantes, Carles Besses, Lourdes Florensa
Journal: Blood (2008)
Abstract 1807: Nuclear targeted gold nanoparticles for radiation enhancement
Authors: James F. Hainfeld, Henry M. Smilowitz
Journal: Cancer Research (2015)

Abstract Gold nanoparticles (AuNP) have been shown to enhance radiation dose (Hainfeld et al, 2004) resulting in significant improvement in tumor control (Hainfeld et al 2008, 2010, 2012). AuNPs that target nuclear DNA have the potential to greatly improve such radiation dose enhancement due to the utilization of the cascade of low energy Auger electrons that follow x-ray absorption. If the AuNP binds to the DNA, these high LET electrons should greatly augment double strand breaks and tumor cell killing. While positively charged peptides are known to take NP into the cell nucleus, they are expensive and subject to proteolytic degradation. We reasoned that just putting a positive charge on the AuNP might mimic enhanced cellular uptake, endothelial escape and nuclear translocation. Such three nm AuNPs had high cell uptake but were retained in the endosome with none getting into the nucleus whereas one nm positively charged AuNPs were found in the cell nucleus and nuclear membrane as well as the cytoplasm as evidenced by light and electron microscopy. Nuclear-localized positively charged AuNPs were found predominantly over regions of heterochromatin. Cells incubated with positively charged AuNPs in vitro and then irradiated showed an increased number of H2AX binding sites as evidenced by fluorescence. Cell metabolism assays using MTT, a surrogate for cell viability, performed one, two and three days following radiation therapy, showed that cells irradiated after loading with positively charged, nuclear targeted AuNPs manifested some decrease in cell viability. Citation Format: James F. Hainfeld, Henry M. Smilowitz. Nuclear targeted gold nanoparticles for radiation enhancement. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1807. doi:10.1158/1538-7445.AM2015-1807
Development of Patient-Reported Bortezomib-Induced Peripheral Neuropathyin Multiple Myeloma Patients Undergoing Induction Therapy
Authors: Xin Shelley Wang, Qiuling Shi, Charles S Cleeland, Tito R Mendoza, Lori Williams, Jacqueline Joy, Venus M Ilagan, Gary M Mobley, Katherine R Gilmore, Robert Z Orlowski
Journal: Blood (2011)
Brain natriuretic peptide usefulness in very elderly dyspnoeic patients: the BED study
Authors: Matthieu Plichart, Galdric Orvoën, Patrick Jourdain, Laurent Quinquis, Joël Coste, Michele Escande, Patrick Friocourt, Elena Paillaud, François-Xavier Chedhomme, Florian Labourée, Clémence Boully, Athanase Benetos, Jean-Jacques Domerego, Michel Komajda, Olivier Hanon
Journal: European Journal of Heart Failure (2016)
A New Microparticle Coagulant Activity Assay to Predict Venous Thromboembolism in Patients with Pancreatic Cancer
Authors: Nick van Es, Suzanne Bleker, Ankie Kleinjan, Rene Berckmans, J W Wilmink, Rienk Nieuwland, Saskia Middeldorp, Harry R Büller
Journal: Blood (2014)
NOD2 Regulates Hematopoietic Cell Function During Graft-Versus-Host Disease.
Authors: Olaf Penack, Odette M. Smith, Nury Yim, Uttam Rao, Arnab Ghosh, George F Murphy, Amanda M. Holland, Robert R. Jenq, Sydney X Lu, Il-Kang Na, Marcel R.M. van den Brink
Journal: Blood (2009)
Abstract 969: B-Raf activation loop phosphorylation is crucial for efficient MAPK signalling in vivo
Authors: Martin Koehler, Michael Roering, Sandra Braun, Tilman Brummer
Journal: Cancer Research (2015)

Abstract Raf proteins are evolutionary conserved protein serine/threonine kinases and represent the MAPKKKs of the ERK-pathway. This pathway plays a crucial role in embryogenesis and is deregulated in multiple diseases. B-Raf represents the most potent MEK kinase of the Raf family and mutations in B-Raf or its upstream activators (e.g. Ras) are well-described in malignancies. So far, targeting the kinase function directly is flawed by paradoxical ERK activation in presence of oncogenic Ras. Therefore, a better understanding of its activation and finding an alternative targeting strategy is crucial. Phosphorylation of the T599VKS602-motif within the B-Raf activation loop is essential for full in vitro kinase activity stimulated by oncogenic Ras and is mimicked by oncogenic mutations such as V600E. To validate the importance of activation loop phosphorylation in vivo, we established a novel conditional BrafAVKA knock-in mouse that, upon Cre-mediated recombination, expresses the B-RafAVKA protein in which T599 and S602 are replaced by alanine residues. Strikingly and in strong contrast to Braf knock-out mice, homozygous BrafAVKA mice are viable and show no early developmental defects suggesting that kinase impairment but not loss of the protein can be tolerated during embryogenesis. Additionally, these findings suggest that the B-RafAVKA mutant protein does not provoke a paradoxical ERK activation like the kinase dead B-RafD594A. However, neurological abnormalities such as ataxia or aberrant locomotion occur in older animals. This phenotype correlates with decreased MEK/ERK phosphorylation in total brain lysates. Also, signalling capacity of the ERK MAPK module, immediate early gene induction and proliferation are impaired in B-RafAVKA expressing MEFs. Our findings support the concept that T599VKS602-motif phosphorylation is necessary for full B-Raf kinase activity in vivo. Therefore, blocking activation loop phosphorylation could be used to suppress aberrant ERK-pathway activity, e.g. by oncogenic Ras or RTKs, and circumventing paradoxical ERK activation in vivo. Citation Format: Martin Koehler, Michael Roering, Sandra Braun, Tilman Brummer. B-Raf activation loop phosphorylation is crucial for efficient MAPK signalling in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 969. doi:10.1158/1538-7445.AM2015-969
Hematopoietic Stem Cell Defects in Novel Fanconi Anemia Mouse Models
Authors: Kalindi Parmar, Jung Min Kim, Akiko Shimamura, Anna Stuckert, Mary K DeLoach, Kaya Zhu, Peter M. Mauch, Jeffery Kutok, Jon Aster, Koichi Akashi, D. Gary Gilliland, Alan D. D’Andrea
Journal: Blood (2008)
SF3B1 Mutations in CLL Are Equivalent to p53/ATM Dysfunction and Cause Defective Puma Upregulation in Response to Chemotherapy
Authors: Doreen te Raa, Ingrid AM Derks, Dieuwertje M Luijks, Jacoline van Laar, Hanneke Monsuur, Ceri Oldreive, Alexander Jethwa, Jennifer Hüllein, Tatjana Stankovic, Thorsten Zenz, Marinus H.J. Van Oers, Arnon P. Kater, Eric Eldering
Journal: Blood (2012)
Mitochondrial function as a therapeutic target in heart failure
Authors: David A. Brown, Justin B. Perry, Mitchell E. Allen, Hani N. Sabbah, Brian L. Stauffer, Saame Raza Shaikh, John G. F. Cleland, Wilson S. Colucci, Javed Butler, Adriaan A. Voors, Stefan D. Anker, Bertram Pitt, Burkert Pieske, Gerasimos Filippatos, Stephen J. Greene, Mihai Gheorghiade
Journal: Nature Reviews Cardiology (2016)
Immunochemotherapy (R-MCP) Is Not Superior to Chemotherapy (MCP) Alone in Advanced Mantle Cell Lymphoma - 42 Months Follow Up Results of the OSHO 39 Study.
Authors: Michael Herold, Antje Haas, Stephanie Srock, Sabine Neser, Kathrin H. Al Ali, Andreas Neubauer, Gottfried Doelken, Ralph Naumann, Thomas Fietz, Mathias Freund, Robert Rohrberg, Klaus Hoeffken, Martin Mohren, Thomas H. Ittel, Erika Kettner
Journal: Blood (2007)
Abstract 4068: <i>In vivo</i> analysis of the residual disease uncovers early and late response of cytarabine-resistant cells in human acute myeloid leukemia
Authors: Jean-Emmanuel Sarry
Journal: Cancer Research (2015)

Abstract The major therapeutic barrier in acute myeloid leukemia (AML) is chemotherapeutic resistance. Resistant cells to conventional chemotherapy - which targets DNA synthesis - are thought to be rare and enriched in quiescent leukemic stem cells. In order to develop an improved understanding of chemotherapy resistance in AML, we analyzed the response to cytarabine (AraC) and disease regrowth in a xenograft model with 13 primary AML patient specimens. After demonstrating AML engraftment, mice are treated with AraC given IP daily for 5 days as a single agent at 60 mg/kg daily, which correlates with human dosing. In all mice treated with AraC, there was a strong cytoreductive effect at 1 week post-treatment with regrowth at 2-8 weeks post-treatment, demonstrating that there is a dose response relationship in the model in terms of nadir leukemic burden and time to relapse. While in vivo AraC increases in hypoxic CD34posCD38neg phenotype, this treatment does not induce any significant changes in cell cycle progression and kills both cycling and quiescent cells in AML-engrafted mice. We also observed that AraC decreases the frequency of leukemia-initiating cells. Furthermore, transcriptomic analysis of residual leukemic cells from three patients-derived xenografts during disease progression (1-2-4 weeks post-AraC) reveals that the AraC resistance is associated with enrichment in genes involved into the apoptosis regulation, inflammatory and metabolism at early stage (1 week), and in stem cell markers with adverse prognosis at the onset of the tumor regrowth (2 week). Altogether, these results suggest a novel model for cytarabine resistance in AML. Citation Format: Jean-Emmanuel Sarry. In vivo analysis of the residual disease uncovers early and late response of cytarabine-resistant cells in human acute myeloid leukemia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4068. doi:10.1158/1538-7445.AM2015-4068