tbuckley/cabot-search huggingface dataset:
Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy
Authors: Eric J. Velazquez, Kerry L. Lee, Robert H. Jones, Hussein R. Al-Khalidi, James A. Hill, Julio A. Panza, Robert E. Michler, Robert O. Bonow, Torsten Doenst, Mark C. Petrie, Jae K. Oh, Lilin She, Vanessa L. Moore, Patrice Desvigne-Nickens, George Sopko, Jean L. Rouleau
Journal: New England Journal of Medicine (2016)

The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear.
Abstract 4319: Lupus antibody-based cancer therapy.
Authors: James E. Hansen, Grace Chan, Yanfeng Liu, Denise C. Hegan, Shibani Dalal, Eloise Dray, Youngho Kwon, Yuanyuan Xu, Xiaohua Xu, Elizabeth Peterson-Roth, Erik Geiger, Yilun Liu, Joseph Gera, Joann B. Sweasy, Patrick Sung, Sara Rockwell, Robert N. Nishimura, Richard H. Weisbart, Peter M. Glazer
Journal: Cancer Research (2013)

Abstract A subset of autoantibodies produced by patients with systemic lupus erythematosus (SLE) penetrates into cell nuclei and binds DNA, and we believe that such antibodies may have applications in cancer therapy. We have discovered that the cell-penetrating, nuclear-localizing anti-DNA lupus antibody 3E10 inhibits key steps in DNA single- and double-strand break repair and has potential for development as a targeted therapy for tumors harboring deficiencies in DNA repair. 3E10 preferentially binds DNA substrates with free single-strand tails and interferes with both base excision repair and homology-directed repair (HDR) in vitro, and HDR efficiency is reduced in cells treated with 3E10 as measured in the chromosome-based DR-GFP fluorescent reporter assay. The binding of 3E10 to DNA can be directly visualized under electron microscopy (EM), and EM studies confirmed that 3E10 interferes with RAD51 filament formation, which is a critical step in HDR. The 3E10 single chain variable fragment penetrates into human tumor xenografts in nude mice, and 3E10 sensitizes cancer cells and tumors to DNA-damaging therapy. In addition, 3E10, by itself, is toxic to BRCA2-deficient cancer cells but not to repair-proficient cells, and when combined with a DNA-damaging agent, 3E10 has a very large cytotoxic effect on BRCA2-deficient cancer cells. The synthetically lethal effect of 3E10 on BRCA2-deficient cancer cells is consistent with our finding that 3E10 inhibits DNA repair, and it suggests that 3E10 has potential as a targeted therapy for tumors harboring deficiencies in DNA repair, such as certain breast, ovarian, and prostate cancers. Of note, patients with SLE have lower than expected incidence rates of breast, ovarian, and prostate cancers, and it is tempting to speculate that the circulating cell-penetrating anti-DNA autoantibodies provide patients with SLE some protection against the development of DNA repair-deficient tumors. In summary, our work with the 3E10 antibody has provided proof of principle for the development of a lupus antibody as a cancer therapy and opened up new avenues for exploration into the biology of lupus antibodies. Citation Format: James E. Hansen, Grace Chan, Yanfeng Liu, Denise C. Hegan, Shibani Dalal, Eloise Dray, Youngho Kwon, Yuanyuan Xu, Xiaohua Xu, Elizabeth Peterson-Roth, Erik Geiger, Yilun Liu, Joseph Gera, Joann B. Sweasy, Patrick Sung, Sara Rockwell, Robert N. Nishimura, Richard H. Weisbart, Peter M. Glazer. Lupus antibody-based cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4319. doi:10.1158/1538-7445.AM2013-4319
P100 The Feasibility Of Using Commercial Multiple Breath Nitrogen Washout Devices In School-aged Children
Authors: E. Raywood, J. Duncan, S. Legg, P. Aurora, J. Stocks
Journal: Thorax (2014)

<h3>Background</h3> Multiple breath inert-gas washout (MBW) using sulphur hexafluoride (SF<sub>6</sub>) measured by mass spectrometry (MS), is sensitive to early lung disease in children with Cystic Fibrosis (CF)<sup>1</sup> but is not widely available. To increase the accessibility of MBW, commercial devices have been adapted using nitrogenwashout (N<sub>2</sub>-MBW). Our aim was to assess the feasibility of two commercial N<sub>2</sub>-MBW devices as supplied by the manufacturers compared to a custom-built MS system in school-aged children. <h3>Methods</h3> Patients with CF and controls performed MBW on three devices; the Exhalyzer<sup>®</sup>D (ECO MEDICS AG); the EasyOne Pro<sup>®</sup>LAB (ndd Medizintechnik AG) and the MS system (AMIS 2000, Innovision ApS) on the same test occasion (order randomised). Attempts were made to obtain 3 technically acceptable runs/device (maximum 8 attempts on each). During testing children watched a DVD and were encouraged to breathe normally. Data were analysed using the ‘clinical application’ setting for both commercial devices, and customised software for the MS. Quality control was in accordance with the ATS/ERS consensus statement<sup>1</sup> and manufacturers’ guidelines. <h3>Results</h3> 14 control (mean[range]age: 15.0[12.5–16.7]yrs) and 18 children with CF (13.5[7.8–17.4]yrs) were assessed. The median (range) number of runs attempted were: MS 3(3–8), Exhalyzer<sup>®</sup>D 4(3–6), EasyOne Pro<sup>®</sup>LAB 4(3–8). Average calibration time was shorter for EasyOne Pro<sup>®</sup>LAB (5 min) than either MS (11 mins) or Exhalyzer<sup>®</sup>D (12 min). Total test duration was similar between devices and dependent on disease severity. 3 acceptable MBW runs were achieved in all children using the MS, 75% with the EasyOne Pro<sup>®</sup>LAB, and 47% on the Exhalyzer<sup>®</sup>D system (see Table). Reasons for failure with Exhalyzer<sup>®</sup>D were usually due to technical/equipment problems, whereas for the EasyOne Pro<sup>®</sup>LAB these were generally associated with marked changes of breathing pattern at commencement of washout, leading to exclusion of one or more runs. <h3>Discussion</h3> Despite use in an experienced MBW centre, our initial attempts to implement commercial MBW devices according to manufacturers’ guidelines resulted in a relatively low success rate in schoolchildren when compared to MS. Subsequent feedback to manufacturers has led to further adaptations which should improve feasibility in future, although this has yet to be assessed in very young children. <h3>Reference</h3> Robinson <i>et al</i>. <i>Eur Resp J</i> 2013
AB0344 Total elbow replacement coonrad-morrey in patients with rheumatoid arthritis
Authors: A. Roskidaylo, A. Logunov, S. Makarov, V. Amirdjanova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> to evaluate effectiveness, the clinical outcomes and quality of life before and after total elbow arthroplasty using semiconstrained prostheses Coonrad-Morrey in patients with rheumatoid elbow. <h3>Methods</h3> Total elbow arthroplasty of 19 elbow was performed on in 18 patients with RA with radiographic changes of Larsen grade 5 or 6 (osteolytic destruction or ankylosis elbow). Patients had severe pain and instability, or absense of moution. We evaluated range of motion and pain. The Mayo Elbow Performance Score and Oxford Elbow Score was used to assess total elbow function; EQ-5D, HAQ – for evaluation quality of life. <h3>Results</h3> The average age of patients was 44,4±14,61 years (20 to 72 years) and there was a 16 female and 2 male (8:1). There were 66,7% seropositive patients. The mean of follow up was 18.5±5,2 months (ranging from 6 months to 3 years). The average duration of RA was 15,0±6,06 years. The average duration elbow complains 8?88±5,23 years. There were pain in 100% patients, synovitis and contrarture of elbow joint. The average increase in flexion was from 102,77±19,75° preoperatively to 116,67°±9,62° and extension was from 51,66±37,04° preoperatively to 24,33°±12,81° at short term follow up (p&lt; 0.05). The average increase in Mayo Elbow Score 37,77/82,2 and Oxford Elbow Score 20,44/39,3 on long term follow up (p &lt; 0.05). The mean EQ-5D (index) score improved from 0,36 to 0,72, HAQ from 1,67 to 1,22; VAS from 48 to 22. There was no neurovascular complication and infection, but in 6 cases (28,57%) were recurrent synovitis. Complications included 2 cases loosening of ulnar component, two cases of ulnar nerve palsy/neurapraxia and 2 cases elbow stiffnes. <h3>Conclusions</h3> Good function can be achieved in the short term with the Coonrad-Morrey-semiconstrained total elbow replacement prosthesis in patients with RA with severe elbow destruction <h3>References</h3> rheumatoid arthritis, elbow arthroplasty <h3>Disclosure of Interest</h3> None Declared
Hyperglucagonemia in Laennec's Cirrhosis
Authors: Robert Sherwin, Prakash Joshi, Rosa Hendler, Philip Felig, Harold O. Conn
Journal: New England Journal of Medicine (1974)

Plasma pancreatic glucagon concentrations were determined in 18 cirrhotic patients in the basal state and after the infusion of alanine, 0.15 g per kilogram of body weight in two to four minutes. In the cirrhotic patients, basal concentrations of glucagon were two to five times normal, and the glucagon response to alanine administration was three to 13 times greater than in 11 control subjects. Glucagon levels were highest in four patients with portacaval anastomosis, were less elevated in 10 cirrhotic patients with spontaneous portal-systemic shunting and were normal in four cirrhotic patients without portal-systemic shunting. Glucagon concentrations correlated closely in all three groups with the degree of ammonia intolerance. Elevations of plasma tyrosine, methionine and phenylalanine were observed in the cirrhotic group, whereas the levels of branched chain amino acids (valine, leucine and isoleucine) were reduced. Hyperglucagonemia may contribute to the glucose intolerance observed in cirrhosis. (N Engl J Med 290:239–242, 1974)
Intraductal papillary mucinous neoplasia with malignant biliary stricture in pancreas divisum
Authors: Angelo Ferrari, Erika Macedo, Fernanda Martins, Maris Souza, Gustavo de Paulo
Journal: Endoscopy (2014)

A 72-year-old man was evaluated because of epigastric abdominal pain and jaundice. His medical history included partial gastrectomy performed for peptic ulcer disease. Physical examination revealed jaundice and an epigastric mass, with tenderness of the upper abdomen. Magnetic resonance imaging revealed a large, mixed cystic and solid mass at the level of the pancreatic head measuring 6.8 × 5.4 cm. The mass resulted in superior mesenteric vein retraction and superior mesenteric artery distortion. There were also multiple pancreatic cysts, suggesting intraductal papillary mucinous neoplasia. In addition, various hepatic nodules were present, as well as enlarged peripancreatic lymph nodes. A positron emission tomography–computed tomography scan revealed uptake by the pancreatic mass, lymph nodes, and multiple hepatic masses ([Fig. 1]). An abdominal ultrasound-guided biopsy of a liver mass confirmed metastatic adenocarcinoma. Because of diffuse disease the patient was referred for palliative biliary endoscopic drainage.
Ortner's Syndrome
Authors: Oscar Prada-Delgado, Eduardo Barge-Caballero
Journal: New England Journal of Medicine (2011)

A 62-year-old woman presented with a 2-year history of progressive vocal hoarseness. She had had mitral-valve replacement for rheumatic mitral stenosis 21 years earlier, but her severe pulmonary hypertension had not resolved, and progressive clinical manifestations had developed.
PMO-255 The expression of interleukin 2 receptor in intestinal resection specimens from patients with Crohn's disease as assessed by immunohistochemistry
Authors: E Russo, G Petts, T Lloyd, R Goldin, P Matthews, T Orchard
Journal: Gut (2012)

<h3>Introduction</h3> Interleukin-2 (IL-2) is a key cytokine in inflammatory pathways involving T-cells. Several studies assess the potential of IL-2 scintigraphy to quantify T-cell infiltrates in conditions such as diabetes, coeliac and Crohn9s Disease (CD). To assess the potential utility of IL-2-based Positron Emission Tomography (PET) radio-ligands that target the IL-2 receptor (IL-2R) in Crohn9s disease imaging, we examined the differential expression of the α-subunit of the IL-2R (CD25) in intestinal resection specimens from patients with CD. <h3>Methods</h3> Stored, formalin-fixed paraffin-embedded blocks from Crohn9s intestinal resection specimens were retrieved. Four 1μm-thick consecutive sections from each block were stained with H&amp;E and CD25 (CD25 1:100, Leica NCL-CD25:305). A pathologist carried out a semi-quantitative grading of acute and chronic inflammation from H&amp;E stained slides attributing a score of 0–3 for each of the two components. Their sum represented the Global Inflammatory Score (GIS). Specimens were subcategorised on the basis of GIS into Group A (GIS 0–1, no or mild inflammation), Group B (GIS 2–4, moderate) and Group C (GIS 5–6, severe). While blinded to the GIS, the pathologist quantified CD25 expression by counting CD25+ve cells in 1mm-wide full thickness regions of bowel wall on slides containing complete, well-orientated mucosa, submucosa and muscularis propria. Results were expressed as CD25+ve cells/mm<sup>2</sup>. Groups were compared using the Mann–Whitney test. In addition, qualitative co-localisation studies of CD25 and CD3 (CD3 1:50 Leica NCL-L-CD3-565) or CD45 (CD45 1:100 Dako M0701) were performed on a sub-selection of six slides. <h3>Results</h3> 12 sets of slides were produced from five resection specimens. A median of 3 (range 2–6) 1 mm wide well orientated bowel wall regions were scored on each slide (total 41). Of these, 15 (37%) were in Group A, 12 (29%) in Group B and 14 (34%) in Group C (see above). Median CD25+ve cell count per mm<sup>2</sup> was 2.04 (range 0.32–6.94), 2.74 (range 0.97–13.86) and 8.89 (range 2.14–59.66) respectively. CD25 was significantly more abundant in Group C than in Group A (p=0.0005) and Group B (p=0.019). The difference in CD25 expression between Groups A and B did not reach statistical significance (p=0.08). Co-localisation studies of CD25 and CD3 or CD45 suggest that the majority, but not all CD25 expression occurs on leucocytes (CD45 positive cells) and specifically T-lymphocytes (CD3 positive cells). <h3>Conclusion</h3> IL2R was significantly more abundant in areas with a severe inflammatory infiltrate, therefore 18F-IL2 PET scanning could be useful in delineating such areas. CD25 appears predominantly but not exclusively expressed on T-cells. <h3>Competing interests</h3> None declared.
VALORACIÓN ENDOSCÓPICA DE LESIONES ANALES EN PACIENTES COINFECTADOS VIH + VPH EN VARONES HSH
Authors: C Alegria-Motte, M López De Hierro Ruíz, C González-Artacho, C Gil Anguita, C Hidalgo Tenorio, J De Teresa Galván
Journal: Endoscopy (2013)

Introducción: El virus papiloma humano (VPH) favorece la displasia y cáncer endoanal. Alta prevalencia en pacientes VIH, HSH. La recto/anuscopia detecta precozmente dichas lesiones y es útil en su seguimiento. Objetivo: Analizar el papel de la recto/anuscopia en el diagnóstico precoz y seguimiento de lesiones endoanales, en HSH, VIH+VPH. Estudio prospectivo observacional. Material y Métodos: Revisamos recto/anuscopias realizadas con endoscopio flexible desde 2009 a pacientes HSH VIH+ con VPH-AR o displasia. Se sometieron a recto/anuscopia con instilación de ácido acético, toma de citología del canal anal y biopsias de lesiones papilomatosas y en los 4 cuadrantes del canal. Resultados: Revisamos 89 pacientes con edad media de 36 años. Tiempo medio de evolución del VIH hasta primera rectoscopia: 63 meses. Colonización de mucosa endoanal por VPH previa anuscopia: 87%, genotipo alto riesgo 72% y solo genotipos de bajo riesgo 22%. Lesiones papilomatosas en primera recto/anuscopia 47%. La citología de recto/anuscopia: negativa en 60%, L-SIL 34% (30) de los cuales 12 sin lesiones endoscópicas y H-SIL en 6% (6) todos con lesiones papilomatosas. Biopsias: negativas 29 (32.6%), AIN1 44(49.4%), AIN2 12(13.5%), AIN3 11(12.4%) y mucosa rectal 2(2.2%). En 23 pacientes realizamos recto/anuscopias copias de control, 6 presentaron mejoría, 12 se mantuvieron estables y 5 progresión de la displasia. De los 89 pacientes: displasia de alto grado CIS 16(18%). El tiempo medio entre el diagnóstico del VIH y la aparición de displasia severa: 52+/-13 meses. Se intervinieron 100%, coincidiendo 87.5% la anatomía patológica de la pieza quirúrgica con la recto/anuscopia. Revisión posterior a cirugía: media de 6 meses: recidiva con displasia 11(68.7%) (2 pendientes de revisión). Reintervenidos 6(54.5%) por persistir displasia de alto grado. Conclusiones: – La toma de biopsias aleatorias y dirigidas durante la recto/anuscopia tiene mayor rentabilidad que la citología por cepillado para la detección de displasia y lesiones de alto grado de malignidad.
Abstract 1587: AMPK-mTOR axis as key target for chemoprevention of UV-induced skin cancer by the bioflavonoid apigenin
Authors: Xin Tong, Bryan B. Bridgeman, Kimberly A. Smith, Michael J. Avram, Jill C. Pelling
Journal: Cancer Research (2012)

Abstract Over two million new cases of UV-induced non-melanoma skin cancer are diagnosed yearly in the USA, making it the most common form of cancer in this country. Apigenin, a nonmutagenic, naturally occurring flavonoid found in a variety of fruits and leafy vegetables, inhibits UV-induced skin cancer in mice. Our laboratory and others have shown that apigenin treatment of cells results in a wide variety of antitumorigenic and chemopreventive actions, including suppression of COX-2 expression, enhancement of p53 expression, and induction of cell cycle arrest and apoptosis. However, the primary target(s) responsible for apigenin's chemopreventive function remains elusive. For the first time, we have demonstrated that apigenin activated AMP-activated protein kinase (AMPK) in keratinocytes (mouse and human keratinocyte cell lines, primary normal human epidermal keratinocytes (NHEKs) and mouse epidermis in vivo). The activation of AMPK resulted in inhibition of mTOR signaling, which relieved the block to the autophagy pathway, further inducing autophagy in human keratinocytes. At early stages of tumorigenesis, autophagy acts as a tumor suppressor by removing damaged organelles, proteins, reducing chromosome instability, and inducing type II programmed cell death. Therefore, pharmacological induction of autophagy provides a new strategy for cancer chemoprevention. We have further demonstrated that UV radiation also induced moderate AMPK activation, suggesting that there is a protective cellular response after UV radiation alone, providing limited protection through modest AMPK activation. More intriguingly, pretreatment of keratinocytes or skin with apigenin prior to UV radiation induced AMPK activation dramatically (both in vitro and in vivo). In addition, UV markedly increased mTOR phosphorylation in SKH-1 mice epidermis, and apigenin completely inhibited UV-mediated mTOR activation. Taken together, our results demonstrate that the AMPK/mTOR axis is involved in chemoprevention of UV-induced skin cancer by apigenin, and mechanistically the activation of AMPK further induces autophagy to suppress UV-induced tumorigenesis. Identifying AMPK-mTOR axis as a key target of apigenin and targeting the autophagy pathway for cancer chemoprevention would provide a new target and strategy for the development of better treatment and prevention of skin cancer. 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 1587. doi:1538-7445.AM2012-1587
Endoscopic continuity-preserving therapy for esophageal stenosis and perforation following colliquative necrosis
Authors: Florian Kuehn, Ernst Klar, Frank Schwandner, Guido Alsfasser, Michael Gock, Leif Schiffmann
Journal: Endoscopy (2014)

Colliquative necrosis after ingestion of an alkaline solution is a very rare and life-threatening clinical picture, which in adults is mainly caused by ingestion either accidentally or with suicidal intent. In cases where severe corrosive injury with transmural necrosis has occurred, esophageal resection may be inevitable. If esophageal salvage is possible, consecutive stenosing scar formation can become a long-term complication. Therefore, timely bouginage is recommended but is also associated with an increased risk of esophageal perforation.
Polypectomy via the Fiberoptic Colonoscope
Authors: William I. Wolff, Hiromi Shinya
Journal: New England Journal of Medicine (1973)

Abstract Polyps of the colon and rectosigmoid, potentially precancerous lesions, have heretofore required laparotomy and colotomy for removal. Against a background experience of 1600 fiberoptic colonoscopies without complication a program in endoscopic removal of colonic polyps from all parts of the colon was undertaken. Three hundred and three polyps, 0.5 to 5.0 cm in diameter, were safely removed by this technic. Bleeding, controlled by transfusion therapy, occurred, in one patient, and minor bleeding in four others.
Priorities for Future IARC Monographs on the Evaluation of Carcinogenic Risks to Humans.
Authors: H Vainio, E Heseltine, J Wilbourn
Journal: Environmental Health Perspectives (1994)

The International Agency for Research on Cancer (IARC) selects chemicals, groups of chemicals, mixtures, physical and biological agents, and exposure circumstances for evaluation in its series L4RC Monographs on the Evaluation of Carcinogenic Risks to Humans on the basis of advice given to them by international groups of scientists.To date, 58 volumes of monographs have been published, providing evluations of 770 agents
Green Tea and the Risk of Gastric Cancer in Japan
Authors: Yoshitaka Tsubono, Yoshikazu Nishino, Shoko Komatsu, Chung-Cheng Hsieh, Seiki Kanemura, Ichiro Tsuji, Haruo Nakatsuka, Akira Fukao, Hiroshi Satoh, Shigeru Hisamichi
Journal: New England Journal of Medicine (2001)

Although laboratory experiments and case-control studies have suggested that the consumption of green tea provides protection against gastric cancer, few prospective studies have been performed.In January 1984, a total of 26,311 residents in three municipalities of Miyagi Prefecture, in northern Japan (11,902 men and 14,409 women 40 years of age or older), completed a self-administered questionnaire that included questions about the frequency of consumption of green tea. During 199,748 person-years of follow-up, through December 1992, we identified 419 cases of gastric cancer (in 296 men and 123 women). We used Cox regression to estimate the relative risk of gastric cancer according to the consumption of green tea.Green-tea consumption was not associated with the risk of gastric cancer. After adjustment for sex, age, presence or absence of a history of peptic ulcer smoking status, alcohol consumption, other dietary elements, and type of health insurance, the relative risks associated with drinking one or two, three or four, and five or more cups of green tea per day, as compared with less than one cup per day, were 1.1 (95 percent confidence interval, 0.8 to 1.6), 1.0 (95 percent confidence interval, 0.7 to 1.4), and 1.2 (95 percent confidence interval, 0.9 to 1.6), respectively (P for trend=0.13). The results were similar after the 117 cases of gastric cancer that were diagnosed in the first three years of follow-up had been excluded, with respective relative risks of 1.2 (95 percent confidence interval, 0.8 to 1.8) 1.0 (95 percent confidence interval, 0.7 to 1.5), and 1.4 (95 percent confidence interval, 1.0 to 1.9) (P for trend=0.07).In a population-based, prospective cohort study in Japan, we found no association between green-tea consumption and the risk of gastric cancer.