tbuckley/cabot-search huggingface dataset:
Hematologically and Genetically Distinct Forms of Sickle Cell Anemia in Africa
Authors: Ronald L. Nagel, Mary E. Fabry, Josee Pagnier, Isidore Zohoun, Henri Wajcman, Veronique Baudin, Dominique Labie
Journal: New England Journal of Medicine (1985)

Patients with sickle cell anemia vary in the hematologic and clinical features of their disease, in part because of variability in the presence of linked and unlinked genes that modify the expression of the disease. The hemoglobin S gene is strongly linked to three different haplotypes of polymorphic endonuclease-restriction sites of the beta-like gene cluster (genes in the vicinity of the beta-globin gene) — one prevalent in Atlantic West Africa, another in central West Africa, and yet another in Bantu-speaking Africa (equatorial, East, and southern Africa). We have studied the differences in the hematologic characteristics of patients with sickle cell anemia from the first two geographical areas. We find that the Senegalese (Atlantic West Africa) patients have higher levels of hemoglobin F, a preponderance of Gγ chains in hemoglobin F, a lower proportion of very dense red cells, and a lower percentage of irreversibly sickled cells than those from Benin (central West Africa). We interpret these data to mean that the gamma-chain composition and the hemoglobin F level are haplotype linked and that the decrease in the percentage of dense cells and irreversibly sickled cells is secondary to the elevation in the hemoglobin F level. Patients with sickle cell anemia in the New World probably correspond to various combinations of these types, in addition to the still hematologically undefined haplotype associated with sickle cell anemia in the Bantu-speaking areas of Africa. (N Engl J Med 1985; 312:880–4.)
CLINICAL RELEVANT EXTRACARDIAC FINDINGS ON NON-CONTRAST ENHANCED CARDIAC COMPUTED TOMOGRAPHY IN THE GENERAL POPULATION: THE HEINZ NIXDORF RECALL STUDY
Authors: Ercan Tezgah, Amir Mahabadi, Marcus Bauer, Kaffer Kara, Iryna Dykun, Susanne Moebus, Karl-Heinz Jöckel, Raimund Erbel, Hagen Kälsch
Journal: Journal of the American College of Cardiology (2015)
National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma
Authors: Pierce K. H. Chow, Su Pin Choo, David C. E. Ng, Richard H. G. Lo, Michael L. C. Wang, Han Chong Toh, David W. M. Tai, Brian K. P. Goh, Jen San Wong, Kiang Hiong Tay, Anthony S. W. Goh, Sean X. Yan, Kelvin S. H. Loke, Sue Ping Thang, Apoorva Gogna, Chow Wei Too, Farah Gillian Irani, Sum Leong, Kiat Hon Lim, Choon Hua Thng
Journal: Liver Cancer (2016)

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26&lt;sup&gt;th&lt;/sup&gt; September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.
Abstract 4473: Urinary biomarkers of exposure to 1,3-Butadiene and its bioactivation to DNA-reactive metabolites
Authors: Srikanth Kotapati, Dewakar Sangaraju, Vernon E. Walker, James A. Swenberg, Natalia Y. Tretyakova
Journal: Cancer Research (2012)

Abstract 1,3-butadiene (BD) is one of the most potent and abundant carcinogens present in cigarette smoke. BD is metabolically activated to 3,4-epoxy-1-butene (EB), 1,2,3,4-diepoxy butane (DEB), hydroxymethylvinylketone (HMVK), and 3,4-epoxy-1,2-butanediol (EBD), which can react with DNA nucleobases and proteins to form promutagenic adducts. Alternatively, these electrophilic metabolites can be detoxified via hydrolysis or conjugation with glutathione. The glutathione conjugates of these metabolites are ultimately excreted in urine as 1-hydroxy 2-(N-acetylcysteinyl)-3-butene (MHBMA), 1,4-bis-(N-acetylcysteinyl)butane-2,3-diol (bis-BDMA), 1,2-dihydroxy-4-(N-acetylcysteinyl)-butane (DHBMA), and 1,2,3-trihydroxy-4-(N-acetylcysteinyl)-butane (THBMA), respectively. Since epoxide metabolites of BD are thought to be responsible for its adverse health effects, it is important to develop specific biomarkers of their formation in vivo to be used in molecular epidemiology studies. While MHBMA, DHBMA, THBMA have been previously detected in smoker's urine, bis-BDMA has not been reported. In the present study, novel stable isotope dilution HPLC-ESI-MS/MS methods for accurate and precise quantification of MHBMA, DHBMA, THBMA, and bis-BDMA in urine have been developed. Dose dependent formation of all BD-mercapturic acids including bis-BDMA was observed in urine samples from male and female F344 rats exposed to 0, 62.5 and 200 ppm of BD for 2 weeks by inhalation. The relative amounts of MHBMA, DHBMA, THBMA, and bis-BDMA in rat urine were 20:50:50:1. Furthermore, MHBMA, DHBMA, and THBMA were detected in urine samples from known smokers and non-smokers, with significantly higher concentrations observed in smokers. The mean levels of these BD-mercapturic acids in smokers were 3, 340, and 27 ng/mg creatinine, respectively. In contrast, bis-BDMA could not be detected in human urine samples, probably a result of the inefficient DEB formation in humans. These methods are now being applied to a multi-ethnic cohort study to identify any differences in metabolism that contribute to ethnic and inter-individual differences in lung cancer incidence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4473. doi:1538-7445.AM2012-4473
Abstract 4767: Reaction of singlet oxygen with hydrazone prodrugs for the photochemical release of N-nitrosoamine drugs
Authors: Ashwini A. Ghogare
Journal: Cancer Research (2012)

Abstract Very few visible-light activated photocleavable groups are available for drug delivery applications. Our research was interested in assessing the visible-light photolability of hydrazone C=N bonds via a Type II (singlet oxygen) dye-sensitized oxygenation reaction. We have explored the photooxidized cleavage of N-nitrosoamine by-products from N-methylbenzophenone phenylhydrazone and methylenehydrazine model compounds. The former was studied by gas chromatography mass spectrometry and the latter by density functional theory calculations (DFT). We quantified benzophenone that arose from the phenylhydrazone photooxidation. The DFT calculations predicted a low energy route to C=N bond fragmentation via a [2+2] pathway and an 1,2,3-dioxazetidine reactive intermediate. The reaction was predicted to occur in stepwise process via zwitterionic intermediates prior to forming the dioxazetidine, and cleavage to the nitrosamine product. Further studies are underway regarding the photolytic and hydrolytic stability of the hydrazone C=N bond to give better insight including structure-activity relationships, of singlet oxygen triggered photo-release of nitrosoamines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4767. doi:1538-7445.AM2012-4767
PTU-156 Hepatocyte Nuclear Factor 4 Alpha (hnf4a) Is Demonstrated In Barrett’s Metaplasia, But Not In Normal Human Oesophagus
Authors: LP Griffiths, Z Burke, JM Farrant, B Colleypriest, D Tosh
Journal: Gut (2014)

<h3>Introduction</h3> Barrett’s metaplasia (BM) is the main risk factor for oesophageal adenocarcinoma, a cancer which carries a mortality of &gt;50% at 12 months. Refluxate containing gastric and bile acids seems to be causative for inflammation at the lower oesophagus, but it is not known how this induces replacement of stratified squamous epithelium (SSQE) with columnar epithelium at a molecular level.There is likely to be a progenitor cell population replacing denuded epithelium, although the origin of these cells has not been proven. Genes that play a role in gut tissue patterning during embryogenesis have received attention. One such ‘master switch’ our laboratory is investigating encodes the hepatocyte nuclear factor 4 alpha (HNF4α) transcription factor. <h3>Methods</h3> We optimised an immunohistochemistry protocol for demonstrating HFN4α on formalin-fixed paraffin-embedded slides of human tissue. This protocol was applied to forceps biopsy specimens of normal oesophagus, gastro-oesophageal junction (GOJ), stomach, ileum, colon and BM (UK REC reference: 13/YH/0197). Tissues were examined from at least 3 different patients per anatomical site. <h3>Results</h3> In healthy tissues, nuclear HNF4α positive immunostaining was demonstrated in stomach, ileum and colonic epithelium, but not in normal SSQE in the oesophagus. At the GOJ, there was clear delineation between HNF4α positive nuclei in the columnar gastric cardia mucosa, and negative HNF4α staining of SSQE. In contrast, the columnar epithelial nuclei in BM were consistently positive. <h3>Conclusion</h3> HNF4α transcription factor is demonstrable in BM, but not SSQE. We are not aware that this HNF4α gastrointestinal distribution has been previously published. HNF4α is likely to be a key transcription factor in the pathogenesis of BM. Previous work in our laboratory with a mouse explant tissue culture model has shown that another candidate transcription factor responsible for BM (Cdx2) was insufficient to induce an intestinal phenotype, whereas HNF4α induced villin, K18, trefoil factor 3 and mucin 5AC. We propose a 2-hit hypothesis for the development of BM: induction of HNF4α (which initially converts the oesophageal SSQE to columnar epithelium) and Cdx2 (which causes intestinalisation of the columnar epithelium). Demonstration of HNF4α in BM but not SSQE is supportive of this theory. <h3>Disclosure of Interest</h3> None Declared.
Milestones in the Staging, Classification, and Biology of Merkel Cell Carcinoma
Authors: Ata S. Moshiri, Paul Nghiem
Journal: Journal of the National Comprehensive Cancer Network (2014)

Merkel cell carcinoma (MCC) is an aggressive skin cancer that is causally associated with ultraviolet light exposure and a recently discovered polyomavirus. Before 2010, MCC was staged using any of 5 unique systems in active use. In 2010, a consensus staging system for MCC was adopted worldwide and replaced these systems. This consensus system includes substages that reflect prognostic differences based on whether nodal evaluation was performed by pathologic analysis or clinical assessment alone. MCC-specific disease classification in ICD-9, to be expanded in the upcoming ICD-10, has improved the ability to track and manage this malignancy. Several biomarkers and histopathologic features have been identified that improve understanding of this cancer and may lead to future refinement of the current staging system. In 2008, the Merkel cell polyomavirus was discovered and is now thought to be a critical mechanism of transformation in at least 80% of MCCs. In patients who produce antibodies to the viral T-antigen oncoprotein, the titer increases and decreases with MCC disease burden and can be a clinically useful marker of recurrence. Diverse studies link CD8-positive T-cell function with outcomes in MCC and serve as the rational basis for ongoing trials of therapies to augment cellular immunity. This article reviews basic and translational research insights that will lead to improved staging, prognostic accuracy, and mechanism-based therapy for this often-lethal skin cancer.
THU0176 12 Week Period May be too Short to Evaluate Clinical Response to Etanercept in RA Patients
Authors: A. Pchelintseva, E. Panasyuk, L. Denisov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Etanercept (ETN) is a fully human TNF-α receptor that is approved for the treatment of rheumatoid arthritis (RA). Several double-blind, placebo-controlled studies demonstrated that ETN was efficacious and safe in treatment RA patients who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs). In some countries guidelines for the antiTNF treatment consider 12 weeks as timepoint to stop or continue therapy. <h3>Objectives</h3> to evaluate time of clinical response to ETN treatment in the patients with RA and optimal timepoint to make a decision to continue or change ETN therapy. <h3>Methods</h3> 188 subjects aging ≥18 years with moderate-to-severe RA despite stable doses of conventional DMARDs received ETN 50 mg weekly subcutaneously for 24 weeks. The mean age was 47,9±13,3; 80,3% (151) were females; the median disease duration was 8,5±7,7 years; 64,9% (122) used methotrexate, 19,1% (36)-leflunomide, 16% (30)-other DMARDs. 44,7% (84) administred low dose of corticosteroids (≤10 mg/day). 31,9% (60) had used another biologics prior to start of ETN.Baseline disease characteristics were (M±SD) : patient pain, VAS (mm): 60,1±18,2; patient disease activity, VAS (mm) : 59,6±18,1; physician disease activity, VAS (mm) : 57,6±13,5; tender joint count 68: 20,7±9,5; swollen joint count 66: 11,9±5,5; tender joint count 28: 13,9±5,5; swollen joint count 28: 9,7±4,1; HAQ: 1,50±0,60; ESR, MM/h: 43,04±22,83; DAS28: 6,26±0,89; CR-P, Mg/l: (Md [Q<sub>25-75</sub>]) 21,3[9,8-37,9]; Disease characteristics evaluated were swollen/tender joint counts (68/66 joints), patient pain and disease activity visual analog scale (VAS), physician disease activity VAS, Health Assessment Questionnarie (HAQ), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) at weeks 0,2,4,12,25. Response was defined as achievement of low disease activity (DAS28≤3.2) or remission (DAS28&lt;2.6) at week 12 and 25; the rate of ACR 20/50/70 responders at weeks 12 and 25 was determined. <h3>Results</h3> Response according to ACR 20/50/70 and EULAR to weeks 12 and 25 <h3>Conclusions</h3> some RA patients had delayed clinical response; they became responders after 3 months of ETN treatment. Although clinicians usually expect rapid effect with biologics, 12 week period may be too short to make a treatment decision about continue or change therapy of ETN. <h3>Disclosure of Interest</h3> None Declared
SAT0264 Impact of uveitis on the phenotype of patients with recent inflammatory back pain. Data from the desir cohort:
Authors: D. Wendling, C. Prati, C. Demattei, C. Miceli-Richard, J.-P. Daures, M. Dougados
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Influence of uveitis on clinical, epidemiological and imaging features in patients with inflammatory back pain (IBP) related to spondyloarthritis (SpA) needs to be known. <h3>Objectives</h3> To determine the prevalence of uveitis in patients with recent IBP suggestive of SpA, and to investigate the influence of uveitis on the overall features of patients presenting with recent IBP. <h3>Methods</h3> The DESIR cohort is a prospective, multicenter French cohort of patients with early IBP (Calin or Berlin criteria) (&gt;3 months and &lt;3 years of duration) suggestive of SpA according to the investigator, including 708 patients (mean age 33.8 years, 53.8% female, 57.3% HLA B27 positive). Uveitis was defined by an ophthalmological episode diagnosed as uveitis by an ophthalmologist, or a painful red eye episode of at least 48 hours duration and/or necessitating local steroids. Data on the baseline demographic characteristics, functional status and quality of life, imaging features (standard X-Rays, MRI, Ultrasounds), BMD, and blood tests were compared in patients with and without uveitis. Both the date of the first symptom of IBP and the symptoms of uveitis were recorded, as well as the date of the visit. Factors associated with the presence of uveitis were identified both by uni and multivariate analysis (logistic regression). <h3>Results</h3> The prevalence of uveitis in the DESIR cohort was 8.47% [95%CI 6.58-10.83] (n=60/708 patients). Uveitis occurred after the first symptoms of IBP in 45%, before in 37%, and simultaneously (±1month) in 18% of the cases. Presence of uveitis was significantly associated in univariate analysis with pain in cervical spine, infection preceding (less than 3 months) inflammatory disease, previous diagnosis of inflammatory bowel disease, some dimensions of SF36 (mental and physical health, relation), presence of Achilles enthesitis, elevated leukocyte count, serum creatinin levels, radiological hip involvement, and chronic sacro iliac MRI lesions. Uveitis is not associated with fulfilment of diagnosis criteria, HLA-B27, BASDAI, BASFI, ASDAS, BMD. A stepwise multivariate analysis found an association between uveitis and: pain in cervical spine, infection preceding inflammatory disease, previous diagnosis of inflammatory bowel disease, physical health limitation of SF36 (Table). <h3>Conclusions</h3> In recent IBP suggestive of SpA, uveitis is associated with some particular rheumatologic and extra rheumatologic features. Our data, and in particular the association with IBD and infection might suggest a role of environmental factors in the incidence of uveitis in SpA. <h3>Disclosure of Interest</h3> None Declared
Congress Focuses on Mammography and Health Care Reform Legislation
Authors: D. A. Tisevich
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Congress Focuses on Mammography and Health Care Reform Legislation Get access Dorothy A. Tisevich Dorothy A. Tisevich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 14, 20 July 1994, Pages 1050–1052, https://doi.org/10.1093/jnci/86.14.1050 Published: 20 July 1994
Pharmacogenomic Modeling in Pancreatic Cancer—Letter
Authors: Amir Avan, Abolfazl Avan, Mina Maftouh, Majid Ghayour Mobarhan, Sharareh Gholamin
Journal: Clinical Cancer Research (2015)

Yu and colleagues ([1][1]) assessed the pharmacogenomics profiling (PGx) of circulating tumorigenic and invasive cells to stratify/predict treatment response in pancreatic ductal adenocarcinoma (PDAC). They suggested the PGx assay as an appropriate tool for choosing a potentially effective targeted
COMPARISON OF PLATINUM CHROMIUM ALLOY AND COBALT CHROMIUM ALLOY EVEROLIMUS-ELUTING STENT IN PATIENTS WITH DE NOVO CORONARY ARTERY LESION: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Shaopeng Xu, Harris Ngow Abdullah, Jae Joong Lee, Sunki Lee, Ji Bak Kim, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2015)
Global Epidemiology — Stocktaking at WHO
Authors: Maxwell Finland
Journal: New England Journal of Medicine (1972)

Each year the President of the United States delivers to the Congress, a message on the State of the Union, reviewing the accomplishments of the government during the preceding year, the major problems old and new that confront the nation, and the status of the various programs designed to cope with those problems. He then presents his proposals for new programs or for improvements in old ones. In spite of his attempts to buoy up our spirits, to impress us with our accomplishments and to instill high hope for the near future, these messages almost always leave many of us . . .
SAT0483 Denosumab Compared with Alendronate in Osteoporotic Postmenopausal Women Previously Treated with Alendronate
Authors: M. Bernad, M. Garcés, E. Martín Mola
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Denosumab is the first biological treatment for osteoporosis in postmenopausal women at high risk of fracture or who have failed, or are intolerant to other osteoporosis treatment. <h3>Objectives</h3> To compare the effect of the treatment with denosumab to alendronate in postmenopausal women with osteoporosis and at high risk of fractures with regard to the variation of bone mineral density (BMD) and the incidence of new fractures. <h3>Methods</h3> This is a longitudinal and prospective study conducted at an outpatient rheumatology division of La Paz University Hospital, Madrid, Spain. Between 126 postmenopausal women ≥65 of age, with severe osteoporosis and history of fractures in most of them, who received 70mg alendronato (ALN) every week for more than two years, 75 patients suspended ALN for different reasons and they signed an informed consent to continue treatment with 60mg denosumab subcutaneously every 6 months. The other patients (n=51) decided to continue with 70 mg ALN every week. All patients received supplements of calcium and vitamin D, according to the individual levels. End points included percentage change from the beginning of the study in lumbar spine (LS) and femoral neck (FN) BMD at month 12 and new fractures incidence by dorsolumbar x-ray and clinic history. <h3>Results</h3> Denosumab-treated women and ALN-treated women were similar age: 73.8±7.1 and 71.7±6.0 years old, respectively. At month 12, significantly greater BMD increase from baseline were observed with denosumab compared with alendronate at LS (6.2±5.7% compared with 3.5±1.6%; p&lt;0.001) and FN (4.3±4.9% compared with 1.9±1.5%; p=0.028). Reasons for ALN suspension were: 41.3% by lack of effectiveness in BMD increasing, 28% by intolerance gastroesophageal, 18.7% for new vertebral fractures, and 12% by decision of the patient. At basal time 62.7% of denosumab-treated women had suffered one or more osteoporotic fractures, after one year were not detected new fractures, all them received 2 doses of denosumab. At baseline, 58.8% ALN-treated women had fractures and after one year one vertebral and two Colles fractures were occurred and 87% of them completed treatment. Poor tolerance to subcutaneous injection or adverse events in any of the two treatment groups were not observed. Denosumab treated women expressed pleasure facility involving the semiannual administration of treatment. <h3>Conclusions</h3> In postmenopausal women with severe osteoporosis previously treated with alendronate, denosumab treatment resulted in greater BMD increases in lumbar spine and femoral neck than alendronate, probably associated with the better adherence due to the highest degree of satisfaction of the patients manifest to receive a six-monthly injection treatment. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2881