tbuckley/cabot-search huggingface dataset:
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Authors: Zheng Zhang, Bin Gao, Fu‐Sheng Wang
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. We fully agree with the suggestions and comments from the letter entitled “Contribution of nonignorable environmental factor to impairing liver disease mortality reduction target in China” by Chao et al. in this issue of Hepatology, which emphasizes the environmental factors partially contributing to increased liver diseases, especially for liver cancer, in China. Frankly, we did not pay much attention to this issue when we were preparing the special article.1 Over the last two decades, exposures to environmental carcinogens of asbestos, arsenic, and in‐ and outdoor air pollution and water and soil pollution have been markedly increased as industrialization expands in China. These exposures have been found to be closely associated with increased liver diseases and are significant risk factors for clustered hepatocellular carcinoma (HCC) mortality in China as well. For example, in the Qidong area of China where HCC is highly prevalent, there are five risk factors associated with high HCC morbidity, such as history of hepatitis B virus infection, familial HCC history, types of drinking water, smoking history, and mental depression. Future studies should comprehensively address the epidemiology of these risk factors and ascertain which environmental factors are main carcinogens, especially in HCC. Occupational exposures are also significant risk factors related to live diseases in China. A number of modifiable occupational exposures have been associated with increased cancer risk, and this has been reflected in several empirical studies using various analytical methods.2 There are also several other exposures that carry a heavy risk for cancer outcomes, including silica, heavy metals, benzene, and diesel engine exhaust. Effects of those exposures have not been fully studied owing to varying country‐specific limitations, some of which include lack of resources and government support. A precise quantification of the burden of human HCC attributable to environmental and occupational exposures is uncertain. In addition, the increases of an aging population in China will also possibly lead to rising total HCC morbidity, even though HCC morbidity remains stable in young people. Taken together, although we have made great progress in the basic research on liver disease with the support of national and regional government funding, there is a long way to go to achieve effective and better management of liver diseases in China. Particularly, we should strengthen national and global collaborative research on “a real non‐neglectable approach of the entire society, involving multidisciplinary work of hepatologists, surgeons, industrialists, and environmentalists and, especially, effective and visionary governance, as well as enlightenment of patients’ awareness and public participation.”
PTH-054 Head to head comparative audit of peg vs rig: a single centre experience
Authors: N E Burch, V M Gordon, J A D Stewart, M Elabassy
Journal: Gut (2010)

<h3>Introduction</h3> Percutaneous endoscopic gastrostomy (PEG) placement has been a well recognised method for delivery of enteral nutrition for many years. A more recent and less invasive alternative has been radiologically inserted gastrostomy (RIG). Although both are accepted methods for enteral feeding, there is a lack of direct comparative data of the two techniques. Current practice is case dependent with lack of evidence based guidelines regarding appropriate choice of procedure. <h3>Methods</h3> A 1-year retrospective analysis of all PEG and RIG procedures undertaken within the University Hospitals Leicester NHS Trust between September 2007 and 2008. Patients were identified using endoscopy records; radiology records; and Nutrition Nurse files. Notes from all those identified were retrieved and reviewed. A patient satisfaction questionnaire was posted to all surviving patients to evaluate the patient experience. <h3>Results</h3> 129 PEGs and 49 RIGs were identified. Notes were reviewed in 75% PEGs (n=97), and 67% RIGs (n=33). Patient demographics were similar in both groups. Main indication for PEG was CVA or neurodegenerative disorders (46% all PEG procedures). In contrast, the most common indication for RIG placement was oesophageal carcinoma or ENT pathology (42% all RIG placement). 18% RIGs were inserted due to displacement of existing tube or blockage. Complications were more common in the RIG placement patients (48% vs 8% for PEG). Main complications in RIGs vs PEGs included displacement (12% vs 1%), unsuccessful placement (8% vs 2%), blocked tube (6% vs 0%), symptomatic hypotension (6% vs 0%), and abdominal pain/vomiting (4% vs 2%). 30-Day Mortality was 0.8% in the PEG cohort, and 2% in the RIG cohort. Patient Experience: Only 31% PEG (36/116) and 13% RIG (5/39) returned a completed questionnaire. Patients reported greater discomfort in the PEG group, with 17% indicating moderately severe/severe pain during the procedure. No responders in the RIG cohort indicated this level of discomfort but there was no indication of type or quantity of analgesia used. <h3>Conclusion</h3> There appears to be a greater risk of complication following RIG placement compared to PEG placement, with higher overall 30-day mortality. It is acknowledged that these groups are not directly comparable, and the higher mortality rate in the RIG group may reflect the underlying disease process. The high rates of displacement or blockage of RIG are also of concern, and further research should evaluate most effective type of RIG for placement. There is a need for a robust prospective randomised controlled trial evaluating PEG placement vs RIG placement for provision of nutritional support. This will be vital for subsequent generation of evidence based guidelines and enable patients to be fully informed regarding the options for feeding.
Elevated Cytosolic Cyclic AMP Inhibits Platelet Adhesion to Von Willebrand Factor by Disengaging the Glycoprotein Ib-IX-V Complex From Lipid Rafts
Authors: Adam D Munday, Rebecca A Penkala, Pavel D Davizon, Clyde J Pierce, William E Hobbs, John D Kulman, Wendy E Thomas, Jose A. Lopez
Journal: Blood (2010)
Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures
Authors: Yasin Şenbabaoğlu, Ron S. Gejman, Andrew G. Winer, Ming Liu, Eliezer M. Van Allen, Guillermo de Velasco, Diana Miao, Irina Ostrovnaya, Esther Drill, Augustin Luna, Nils Weinhold, William Lee, Brandon J. Manley, Danny N. Khalil, Samuel D. Kaffenberger, Yingbei Chen, Ludmila Danilova, Martin H. Voss, Jonathan A. Coleman, Paul Russo, Victor E. Reuter, Timothy A. Chan, Emily H. Cheng, David A. Scheinberg, Ming O. Li, Toni K. Choueiri, James J. Hsieh, Chris Sander, A. Ari Hakimi
Journal: Genome biology (2016)

Tumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types. We compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8+ T/Treg ratio are associated with improved survival, whereas Th2 cells and Tregs are associated with negative outcomes. Investigation of the association of immune infiltration patterns with the subclonal architecture of tumors shows that both APM and T cell levels are negatively associated with subclone number. Our analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC.
A Phase I Study of An Oral Hedgehog Pathway Antagonist, BMS-833923, in Patients with Relapsed or Refractory Multiple Myeloma,
Authors: Carol A. Huff, Swaminathan Padmanabhan, Kevin R. Kelly, George Somlo, Luis Camacho, Jeffrey Zonder, Bruce Fischer, Lixin Lang, Steven Zhang, Toni Gestone, Kelly L. Bennett
Journal: Blood (2011)
AB1095-HPR Evaluation of The Static Foot Function in Patients with Reduced Mobility in The Course of Rheumatic Diseases
Authors: A. Kuryliszyn-Moskal, K. Kaniewska, Z. Dzięcioł-Anikiej, P.A. Klimiuk
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatic diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA), constitute the most frequent pathological states leading to the development of foot deformities, which reduce the quality of life and cause disability. <h3>Objectives</h3> The aim of the present study was to compare the results of plantoconturographic examination, obtained by means of a computer podoscope, in OA and RA patients. Special attention was paid to the differences in the values of each parameter determining the level of foot function. <h3>Methods</h3> The study was conducted on 94 female patients divided into two groups according to the type of disease. There were 54 patients with RA and 40 with OA. The control group consisted of 34 healthy women. The plantographic assessment of static foot structure was carried out by means of a device for computer-aided foot examination. <h3>Results</h3> A fallen transverse arch of the right foot was statistically much more frequent in the RA patients than in OA patients or the control group. Significant differences in the values of the Wejsflog index were observed between RA patients and the control group. Similarly, there were statistically significant differences in the values of the hallux valgus angle (α) for the right foot between RA and OA patients vs. the control group, as well as between OA patients and the control group. <h3>Conclusions</h3> Rheumatic diseases predispose patients to the disturbances of static foot function. The obtained results highlight the importance of diagnosing foot statics disorders in the prevention of destructive changes affecting the functioning of OA and RA patients. <h3>Acknowledgement</h3> foot function, mobility, plantoconturography, RA patients, OA patients <h3>Disclosure of Interest</h3> None declared
Perifosine Plus Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients Previously Treated with Bortezomib: Final Results of a Phase I/II Trial
Authors: Paul G. Richardson, Jeffrey Lee Wolf, Andrzej J. Jakubowiak, Jeffrey A. Zonder, Sagar Lonial, David Irwin, John Densmore, Amrita Krishnan, Noopur S. Raje, Michael H. Bar, Robert Schlossman, Irene M. Ghobrial, Nikhil C. Munshi, Thomas Martin, Jacob P. Laubach, Jeffrey P Allerton, Teru Hideshima, Peter Sportelli, Lesa Gardner, Kenneth C. Anderson
Journal: Blood (2011)
CLAG±M (cladribine, cytarabine, granulocyte colony stimulating factor ± mitoxantrone) Results in High Response Rates in Older Patients with Secondary and Relapsed/Refractory Acute Myeloid Leukemia - a Single Institute Experience
Authors: Monica Reddy Muppidi, Craig W. Freyer, Laurie Ann Ford, Evelena P Ontiveros, James E. Thompson, Elizabeth A. Griffiths, Eunice S. Wang
Journal: Blood (2015)
Natural Killer-Like T (NKT) Cells with Specific T Cell Receptor (TCR) Sequences May Be Causally Implicated in the Pathogenesis of Paroxysmal Nocturnal Hemoglobinuria (PNH).
Authors: Lucia Gargiulo, Gianna Cerruti, Sonia Lastraioli, Daniele Reverberi, Simona Zupo, Lucio Luzzatto, Rosario Notaro
Journal: Blood (2004)
Pre-Transplant Rituximab Therapy Is Associated with Improved Progression-Free and Overall Survival in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma (DLBCL).
Authors: Timothy S. Fenske, Parameswaran Hari, Jeanette Carreras, Mei-Jie Zhang, Rammurti Kamble, J. Douglas Rizzo, Koen van Besien, Hillard M. Lazarus, Julie M. Vose
Journal: Blood (2007)
Ganglioside GM3: An anti-angiogenic molecule with therapeutic potential
Authors: Purna Mukherjee, Anthony Faber, Laura Shelton, Rena Baek, Jeremy Marsh, Thomas Chiles, Thomas Seyfried
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

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Gangliosides are sialic acid-containing glycosphingolipids that have long been associated with tumor malignancy and metastasis. Mounting evidence suggests that gangliosides also modulate tumor angiogenesis. Tumor cells shed gangliosides into the microenvironment, which then produce both autocrine and paracrine effects on tumor cells and tumor associated host cells (Liu et al., Cancer Res., 66: 10408-14, 2006; and Abate et al., J Neurochem, 98:1973-84, 2006). We previously showed that genetic changes in the ratio of the simple monosialo-ganglioside, GM3, to the complex disialo-ganglioside, GD1a, modulated angiogenesis in mouse brain tumors. In this study, we show that GM3 counteracts the pro-angiogenic effects of vascular endothelial growth factor (VEGF) and GD1a. GM3 significantly inhibited the action of VEGF and GD1a on the proliferation of human umbilical vein endothelial cells (HUVEC), and inhibited the migration of HUVEC towards VEGF as a chemoattractant. Enrichment of added GM3 in the HUVEC membrane also reduced phosphorylation of VEGF receptor 2 (VEGFR-2) and downstream Akt. Moreover, GM3 significantly reduced the pro-angiogenic effects of GD1a in the in vivo Matrigel plug assay. Inhibition of GM3 biosynthesis with glucosyl transferase inhibitor, N-butyldeoxynojirimycin (NB-DNJ), significantly increased HUVEC proliferation and VEGFR-2 and Akt phosphorylation suggesting that endogenous GM3 influences angiogenic signaling. Addition of GM3 reversed the effects of NB-DNJ in HUVEC. We conclude that GM3 has anti-angiogenic action and could have therapeutic potential for reducing tumor angiogenesis. (The research was supported from NIH grants (NS 055195 and CA102135), and the Boston College research expense fund).
Detection of lesions in dysplastic Barrett’s esophagus by community and expert endoscopists
Authors: Dirk Schölvinck, Kim van der Meulen, Jacques Bergman, Bas Weusten
Journal: Endoscopy (2016)

Background and aims Endoscopic treatment of Barrett's esophagus (BE) consists of endoscopic resection of visible lesions followed by radiofrequency ablation (RFA) for any remaining flat BE. Because RFA is only justified in flat BE, detection of neoplastic lesions (high grade dysplasia [HGD] and early adenocarcinoma [EAC]) is crucial. We hypothesized that the detection of visible lesions containing HGD or EAC would be superior in BE expert centers compared with community hospitals, thereby supporting centralization of therapy for BE-related neoplasia. Methods Patients referred with histologically proven HGD or EAC to two Dutch BE expert centers were included. Referral letters, and endoscopy and pathology reports were reviewed for the description of the BE, presence of lesions, and histopathological analysis of target and random tissue sampling. Primary outcome was the endoscopic detection rate of lesions containing histopathologically proven neoplasia (HGD and/or EAC) in community and expert centers. Results There were 198 patients referred from 37 community hospitals (median referral time 55 days [interquartile range 33 - 85]). Detection rates for visible lesions were 60 % in community centers (75 % in patients with a biopsy diagnosis of EAC, 47 % in HGD) and 87 % in expert centers (98 % in EAC, 75 % in HGD); P < 0.001. Even with HGD/EAC on random biopsies from the index endoscopy, the yield at repeat endoscopy was < 50 % in community hospitals. In 79 patients referred solely because of random biopsy results, a lesion requiring endoscopic resection or surgery was found in 76 % by the expert endoscopists. Conclusions Endoscopists at community hospitals detect neoplastic lesions at a significantly lower rate. These data support the value of BE expert centers for work-up and further treatment of BE.
A Novel Strategy to Circumvent Pre-Existing Humoral Immunity to AAV
Authors: Federico Mingozzi, Xavier M Anguela, Giulia Pavani, Yifeng Chen, Robert J Davidson, Daniel J. Hui, Christian J Hinderer, Armida Faella, Crolann Howard, Alex Tai, Gregory M Podsakoff, Margaret V. Ragni, Shangzhen Zhou, Etiena Basner-Tschakarjan, J. Fraser Wright, Katherine A. High
Journal: Blood (2012)
Hypoxia Activated Prodrug TH-302 for the Treatment of Multiple Myeloma.
Authors: Jinsong Hu, Damian R Handisides, Els Van Valckenborgh, Hendrik De Raeve, Eline Menu, Isabelle Vande Broek, Qian Liu, Jessica D Sun, Ben Van Camp, Charles Hart, Karin Vanderkerken
Journal: Blood (2009)
Prognostic Value of Pre-Transplant PET Scan in Patients with Diffuse Large B-Cell (DLBCL) Lymphoma Undergoing Autologous Stem Cell Transplantation (ASCT)
Authors: Allison M Winter, Lisa A. Rybicki, Shetal Shah, Deepa Jagadeesh, Aaron T. Gerds, Betty K. Hamilton, Hien Liu, Robert M. Dean, Ronald Sobecks, Brad Pohlman, Steven Andresen, Mitchell R. Smith, Matt Kalaycio, Brian J. Bolwell, Navneet S. Majhail, Brian T. Hill
Journal: Blood (2015)
Blood Hypercoagulation Assessed with Thrombodynamics Test Predicts Postoperative Venous Thrombosis in Patients at High Risk
Authors: Kirill Lobastov, Galina Dementieva, Natalia Soshitova, Victor Barinov, Leonid Laberko, Grigory Rodoman, Valeriy Boyarintsev
Journal: Blood (2015)
Diminished Vasculogenic Function of Bone Marrow-Derived CD133+ Endothelial Precursor Cells (EPC) Obtained from Advanced Aged Patients with Coronary Artery Disease
Authors: Nicholas J Greco, Marcie Finney, Laura Fanning Hammond, Margie Kozik, Matthew Joseph, Shyam Bhakta, Peter Haviernik, Mathew Lesniewski, Jonathan Goldberg, Paul Scheid, Aaron Victor, Vincent Pompili, Mary J Laughlin
Journal: Blood (2008)
FRI0169 Influence of Body Mass Index (BMI) on Serum Levels of Infliximab in Patients with Rheumatoid Arthritis (RA):
Authors: A. Villalba Yllan, M.V. Navarro Compan, C. Plasencia Rodriguez, D. Peiteado Lopez, G. Bonilla Hernan, L. Nuño Nuño, D. Pascual-Salcedo, E. Olariaga, A. Balsa Criado, E. Martin Mola
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Loss of response of TNFα inhibitors (TNFi) over time resulting in discontinuing of this therapy is a major issue in RA, but underlying reasons for this remains unknown. A few studies suggest the influence of BMI on serum levels of subcutaneous TNFi. However, there is no available data on the possible influence of BMI on infliximab (IFX) serum levels, which is intravenously administred and adjusteing the dose according to patient weight. <h3>Objectives</h3> To determine the possible influence of BMI on serum IFX levels in patients with RA. <h3>Methods</h3> Retrospective observational study incluiding 72 patients with RA treated with infliximab, at 3 mg/kg dose in a standard regimen, in our department between 2000 and 2015. Serum IFX levels were determined by ELISA in 3 visits: i)2 weeks, ii)six months and iii)one year after treatment onset. BMI (kg/m<sup>2</sup>) was classified in four categories: underweight (&lt;18,5), normal (≥18,5- &lt;25), overweight (≥25- &lt;30) and obesity (≥30). Descriptive analysis was used to compare drug levels between these four groups at each visit. To analyse the relationship between BMI and IFX drug levels, generalized estimation equation models adjusted for age, gender and concomitant treatment were employed. <h3>Results</h3> Characteristics of patients included in the study when initiating IFX therapy were: 88% female, median (range) age 52 (21–82) years, 71% RF+, 79% ACPA+, disease duration 10,4 (1,0–39,0) years, 79% with concomitant methotrexate and 57% with other DMARDs. Median (range) BMI was 25,5 (16,7–40,2) kg/m<sup>2</sup>. According to BMI, patients with underweight, normal, overweight and obesity were 2 (2,7%), 35 (48,6%), 23 (31,9%) and 12 (16,7%), respectively. Median (range) IFX serum levels, in ng/ml, for each of the four BMI categories,and for each of the visits, are presented in Table 1. In the longitudinal analysis, an inverse statistically significant relationship between BMI and drug serum levels was observed: β: -441,7; 95%CI (-829,7 to -53,8). This relationship remained despite of adjusting the model for potential confounders: β: -457,3; 95%CI (-858,8 to -55,8). <h3>Conclusions</h3> BMI influences serum IFX levels in patients with RA treated with infliximab. Higher BMI values are associated with lower serum drug levels. <h3>Acknowledgement</h3> Unrestricted grants from Pfizer <h3>Disclosure of Interest</h3> None declared
Targeting the Hedgehog Signaling Pathway By PF-04449913 Limits the Self-Renewal of MDS-Derived Induced Potent Stem Cells (iPSC): Molecular Mechanisms
Authors: Tetsuzo Tauchi, Seiichi Okabe, Seiichiro Katagiri, Yuko Tanaka, Kaoru Tohyama, Kazuma Ohyashiki
Journal: Blood (2015)
Management of Obesity
Authors: Naji Alamuddin, Zayna Bakizada, Thomas A. Wadden
Journal: Journal of Clinical Oncology (2016)

This review examines weight loss and accompanying improvements in obesity-related comorbidities produced by intensive lifestyle intervention, pharmacotherapy, and bariatric surgery. Obese individuals lose approximately 6 to 8 kg (approximately 6% to 8% of initial weight) with 6 months of participation in a high-intensity lifestyle intervention (≥ 14 treatment visits) consisting of diet, physical activity, and behavior therapy. Such losses reduce progression to type 2 diabetes in at-risk people and decrease blood pressure and triglyceride levels. All diets, regardless of macronutrient composition, can produce clinically meaningful weight loss (&gt; 5%) if they induce a deficit ≥ 500 kcal/d. Physical activity of 150 to 180 min/wk yields modest short-term weight loss compared with diet but contributes to improvements in obesity-related conditions. Gradual weight regain is common after lifestyle intervention but can be prevented by continued participation in monthly weight loss maintenance sessions, as well as by high levels of physical activity (ie, 200 to 300 min/wk). Patients unable to reduce satisfactorily with lifestyle intervention may be candidates for pharmacotherapy, recommended as an adjunct. Five medications have been approved by the US Food and Drug Administration for chronic weight management, and each has its own risk/benefit profile. The addition of these medications to lifestyle intervention increases mean weight loss by 2.5 to 8.9 kg compared with placebo. Patients with severe obesity who are unable to reduce successfully with lifestyle intervention and pharmacotherapy are eligible for bariatric surgery, including Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding. The first two procedures yield long-term (≥ 3 years) reductions of ≥ 20% of initial weight that are associated with decreases in morbidity and potentially mortality. Greater resources and dissemination efforts are needed to increase the availability of these three approaches for the millions of Americans who would benefit from them.
Prospective Oral Mucositis Audit (POMA): Occurrence and Consequences of Severe Oral Mucositis in High Dose Melphalan and BEAM Conditioning.
Authors: Nicole N.A. Blijlevens, Shaun McCann, Pam Bacon, Roisín Cinnéide, Barry Quinn, Ann Roosaar, Harry Schouten, Matthias Schwenkglenks, Rebecca Stone
Journal: Blood (2006)