tbuckley/cabot-search huggingface dataset:
PWE-005 Outcomes from the first uk bowel cancer screening programme (bcsp) site: screening and surveillance experience since 2006
Authors: H Padmanabhan, MJ Brookes, B McKaig, A Murugananthan, M Mangalika, M Widlak, L Ford, A Veitch
Journal: Gut (2015)

<h3>Introduction</h3> National BCSP screening for all 60–69 year olds commenced in 2006, and was extended to 60–74 year olds in 2010. The first site open was in Wolverhampton in July 2006. Previous trials had demonstrated the efficacy of population screening with the use of faecal occult blood test. We have previously shown that in the first two years of the BCSP downstaging of colorectal cancer in the screened group was demonstrated (45.3% Dukes A and 21.7% Dukes B).<sup>1</sup> <h3>Method</h3> Retrospective analysis of data from the first 7 years of the programme (August 2006 to December 2013) included demographics, screening outcomes (neoplasia and adenoma detection), pathological staging of cancers and colonoscopy quality indicators. Surveillance outcomes were reported on those patients eligible in the study period. <h3>Results</h3> During the study period (2006–13) 4506 colonoscopies were undertaken (63.4% Male; n = 2855). Mean caecal intubation rate was 97.1% and mean withdrawal time for normal procedures was 7.3 min. 355 cancers were detected (65.3% Male; n = 232). 62.5% of cancers were ‘early’ (23% Dukes A, 31.5% Dukes B) and 71.5% were left-sided (28% rectal, 37.4% sigmoid). 3699 adenomas were detected and the mean number of adenomas per procedure was 0.82. 37% (n = 1366) of these were 1 cm. The mean adenoma detection rate per colonoscopist was 43.25%. The high risk (n = 420) and intermediate risk (n = 768) adenomas were surveyed as per national guidance. In those high risk surveillance cases (n = 420) the detection of adenoma was seen in 31.4% (n = 132) of which 13.6% (n = 18) of them had adenomas greater than 1 cm. 0.47% (n = 3) of surveillance cases were found to have cancer suggestive of a potential post colonoscopy missed cancer. <h3>Conclusion</h3> These data confirm that a high quality screening colonoscopy service has been maintained since inception of the BCSP. Despite high quality indicators for endoscopic performance, surveillance has demonstrated missed adenoma and cancer still occur. Cancer staging data suggest a diminished benefit in the latter 5 years of the BCSP. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Ellul P, Fogden E, Simpson CL, <i>et al</i>. Downstaging of colorectal cancer by the national bowel cancer screening programme in England: first round data from the first centre. Colorectal Dis. 12:420–422
Calcineurin Orchestrates Lateral Transfer of <i>Aspergillus fumigatus</i> during Macrophage Cell Death
Authors: Anand Shah, Shichina Kannambath, Susanne Herbst, Andrew Rogers, Simona Soresi, Martin Carby, Anna Reed, Serge Mostowy, Matthew C. Fisher, Sunil Shaunak, Darius P. Armstrong-James
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis.Objectives: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants.Methods: We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies.Measurements and Main Results: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell–cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape.Conclusions: These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.
Secukinumab long-term safety experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis
Authors: Peter C.M. van de Kerkhof, Christopher E.M. Griffiths, Kristian Reich, Craig L. Leonardi, Andrew Blauvelt, Tsen-Fang Tsai, Yankun Gong, Jiaqing Huang, Charis Papavassilis, Todd Fox
Journal: Journal of the American Academy of Dermatology (2016)
Reduction in Responsiveness of Thymocytes to Phytohemagglutinin During Bladder Tumor Induction and Restorative Effects of Thymosin Fraction 5 in Rats
Authors: Seiji Wada, Yoshihiro Kinoshita
 4, Yukichi Ozaki, Shoichi Nishio, Shuhei Kimura, Masanobu Maekawa
Journal: JNCI Journal of the National Cancer Institute (1987)

Urinary bladder tumors were induced in female Wistar rats by oral administration of N-butyl-N-(4-hydroxybutyl) nitrosamine [(BBN) CAS: 3817-11-6]. Hypertrophy or vascular formation was observed in the bladder membrane 8 weeks after BBN administration, and tumors became visible at the 15th week. At the 20th week, approximately 95% of these rats had bladder tumors. The response of thymus lymphocytes to phytohemagglutinin (PHA) in these BBN-treated rats began to decrease from the 10th week and decreased significantly from the 18th week as compared with that in untreated rats. This reduced response to PHA was slower in comparison with the reduced response to concanavalin A. When thymus lymphocytes were preincubated with thymosin fraction 5 in vitro, the response to PHA improved between the 8th week and the 20th week. Furthermore, when the thymus small lymphocyte population was separated into 3 subpopulations by discontinuous density gradient centrifugation and an adhesion column, the restorative effect of the thymus hormonal product was greater in the intermediate and heavier subpopulations.
Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy
Authors: Vijay G. Bhoj, Dimitrios Arhontoulis, Gerald Wertheim, James Capobianchi, Colleen A. Callahan, Christoph T. Ellebrecht, Amrom E. Obstfeld, Simon F. Lacey, Jan J. Melenhorst, Farzana Nazimuddin, Wei-Ting Hwang, Shannon L. Maude, Mariusz A. Wasik, Adam Bagg, Stephen Schuster, Michael D. Feldman, David L. Porter, Stephen A. Grupp, Carl H. June, Michael C. Milone
Journal: Blood (2016)
Abstract 658: Suppressed Hypoxic Pulmonary Vasoconstriction in Malonyl-CoA-Decarboxylase Knock-Out Mice
Authors: Gopinath Sutendra, Sebastien Bonnet, Alois Haromy, Gary Lopaschuk, Jason Dyck, Evangelos D Michelakis
Journal: Circulation (2007)

Background : Hypoxic pulmonary vasoconstriction (HPV) is intrinsic to the pulmonary artery smooth muscle cells (PASMC). A recently proposed mechanism for HPV suggests that hypoxia is sensed within the mitochondria, altering the production of activated oxygen species (AOS) in response to changes in PO 2 . Decreased AOS (like H 2 O 2 ) inhibit Kv channels, depolarize PASMC, increase influx of Ca ++ , causing PASMC contraction. Malonyl-CoA-Decarboxylase (MCD) is a metabolic enzyme, that when inhibited suppresses the mitochondrial-based fatty acid oxidation, promoting glucose oxidation. We have shown that knockout mice lacking MCD (KO-MCD) are resistant to chronic-hypoxia-induced pulmonary hypertension (CH-PHT) but they have a normal phenotype in normoxia. We hypothesized that KO-MCD mice have suppressed HPV. Methods and Results : We compared KO-MCD to wild mice (W-MCD) using PASMC patch clamping, intracellular Ca ++ (fura-2), mitochondrial membrane potential (ΔΨm, using TMRM and confocal microscopy), mitochondrial AOS production (mitosox and confocal microscopy) and isolated intact resistance PA rings; we also studied exercise tolerance (distance covered in a treadmill) during normoxia and acute hypoxia (n =7–10 mice/group for all studies). As expected, in W-MCD mice acute hypoxia inhibited K + current (Ik), increased intracellular Ca ++ and mitochondrial ΔΨm, decreased mitochondrial AOS production, increased PA tone and decreased exercise tolerance (due to the rapid increase in PA pressure and decrease in cardiac output). In contrast, KO-MCD showed an impressive lack of response to acute hypoxia in all the parameters studied (table ). Conclusions : Our data show that acute hypoxia is not sensed in W-MCD mice and might offer at least a partial explanation for the resistance to CH-PHT in these mice. They also offer a novel insight into the metabolic basis of pulmonary vascular reactivity and HPV.
Lorenzo Tomatis 1929–2007
Authors: James Huff, Ronald Melnick
Journal: Environmental Health Perspectives (2008)

in Lyon, France, we lost a great human being, a staunch advocate for public health, a thorough and delving scientist, and a humanitarian par excellence.Lorenzo Tomatis, MD, above all, was a learned teacher and creative innovator.His accomplishments are legion, and his far-reaching impact on human health, including the well-being of future generations, will be impossible to replace.Tomatis was clearly a true pioneer and admired leader in primary disease prevention.He stands tall among other giants and trailblazers of environmental health science and public health advocacy including Cesare Maltoni, Norton Nelson,
A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases
Authors: Buhm Han, Jennie G Pouget, Kamil Slowikowski, Eli Stahl, Cue Hyunkyu Lee, Dorothee Diogo, Xinli Hu, Yu Rang Park, Eunji Kim, Peter K Gregersen, Solbritt Rantapää Dahlqvist, Jane Worthington, Javier Martin, Steve Eyre, Lars Klareskog, Tom Huizinga, Wei-Min Chen, Suna Onengut-Gumuscu, Stephen S Rich, Naomi R Wray, Soumya Raychaudhuri
Journal: Nature Genetics (2016)
Clinical Patterns of Palbociclib Associated Neutropenia in the Paloma-1/Trio-18 Trial
Authors: R. Finn, J. Crown, J. Ettl, T. Pinter, M. Schmidt, C. Huang-Bartlett, P. Schnell, S. Kim, S. Randolph, K. Wang, D.J. Slamon
Journal: Annals of Oncology (2014)
Phase 2 Trial of Gemcitabine Plus Uft in Oxaliplatin, Irinotecan and Fluoropyrimidine-Refractory Colorectal Cancer
Authors: Keun-Wook Lee, Yu Jung Kim, Sae-Won Han, Tae-Yong Kim, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, In Sil Choi, Jee Hyun Kim
Journal: Annals of Oncology (2014)
A Phase I Dose Escalation Study Of Oral Bexarotene In Combination With Intravenous Decitabine In Patients With AML
Authors: John Welch, Haixa Niu, Geoffrey L. Uy, Peter Westervelt, Camille N. Abboud, Ravi Vij, Keith E. Stockerl-Goldstein, Meagan Jacoby, Iskra Pusic, Mark A. Schroeder, John F. Dipersio, Amanda F Cashen
Journal: Blood (2013)
Academic calls for MPs to investigate “weekend effect” in view of conflicting evidence
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The House of Commons health select committee is expected to consider holding an investigation into whether patients admitted to hospital at weekends face a greater risk of death than those admitted during the week, after an academic called for a review earlier this week.

The government has argued that evidence of such a “weekend effect” exists and has used this as the basis of its argument for a “seven day” NHS, one of the key issues in its protracted dispute with junior doctors in England over their new contract. In particular, the health secretary for England, Jeremy Hunt, has cited a paper published in The BMJ to push for changes. The paper, by Nick Freemantle of University College London and colleagues, found that 11 000 more people died each year within 30 days of admission to hospital if they were admitted on a Friday, Saturday, Sunday, or Monday than if they were admitted on other days of the week.1 However, this analysis did …
PTU-108 A UK single centre experience of management of hepatitis C virus genotype 4 infection with pegylated-interferon and ribavirin
Authors: N Selvapatt, M Habibi, A Brown
Journal: Gut (2015)

<h3>Introduction</h3> New direct acting antiviral agents are revolutionising hepatitis C virus (HCV) treatment. However, to date published phase 3 clinical trial data in genotype 4 (GT4) HCV patients is limited. GT4 HCV is more common in Africa, the Middle East and Asia. In the UK, the mainstay of treatment has been pegylated interferon and ribavirin but limited data exists on outcomes in patients treated in Europe. We report the first “real-life’ sustained virological response (SVR) outcomes using pegylated interferon and ribavirin for HCV GT4 in the UK, and the largest European single centre cohort. <h3>Method</h3> HCV GT4 patients treated at a London, UK centre between 2002 and 2014 were assessed for SVR outcomes. Patient age, sex, region of origin, co-infection with HIV, pre-treatment liver biopsy histological assessment, genotype subtyping, treatment duration and dose reductions were compared against SVR outcomes on univariate analysis. Multivariate analysis was performed on results with P &lt; 0.1. <h3>Results</h3> During the study period 219 patients were diagnosed with HCV GT4. Of these 118 (54%) were treated with pegylated interferon and ribavirin and 57 achieved SVR (48%). The median age at the start of treatment was 48 years (range 6 to 66 years) and 72% were male. Six patients were intolerant, 25 were non responders, 3 developed breakthrough, 18 were relapsers, 3 are currently undergoing treatment and 6 lost to follow-up. Five out of 6 patients with acute HCV and HIV co-infection achieved SVR. Three HCV monoinfected patients were treated while on renal dialysis, with 2 achieving SVR. On univariate analysis age ≥ 45 (P &lt; 0.0001), high viral load (P &lt; 0.0001), Ishak staging 5–6 (P &lt; 0.0001) and non-Egyptian Africans (P = 0.0059) were all negatively associated with SVR. Eastern Europeans appeared to have higher rates of SVR (P &lt; 0.0001). Using multivariate correlation viral load (P = 0.0005); Ishak staging (P = 0.0031) and age (P = 0.0003) were associated with SVR but not country of origin (P = 0.0645). <h3>Conclusion</h3> Outcomes with pegylated interferon and ribavirin for HCV GT4 in this “real-life” setting were sub-optimal especially in the context of newer regimens. Patients with older age, high viral loads and advanced disease need prioritisation for alternative treatments. <h3>Disclosure of interest</h3> N. Selvapatt Conflict with: Gilead, BMS, M. Habibi: None Declared, A. Brown Speaker Bureau of: Abbvie, BMS, Gilead, Janssen, Merck.
Abstract P064: Weight Loss Induced by Healthy Diets Reduces Atherogenic Lipoproteins that Contain ApoC-III Independent of Dietary Macronutrient Content
Authors: Jeremy Furtado, Vincent Carey, George Bray, Frank Sacks
Journal: Circulation (2013)

Background: Weight-loss improves lipid risk factors for cardiovascular disease risk. However, the effect of weight loss on VLDL, LDL and HDL subtypes that contain apoC-III, newly emerging as important predictors of CVD, is not known. Further, the effects of dietary macronutrient composition on changes in apoC-III-containing lipoproteins in the presence of weight loss have not been studied. Methods: The Pounds Lost Trial randomized 811 overweight and obese subjects to four healthful diets that varied in emphasis of unsaturated fat, protein, and carbohydrate for 24 months. A random 50% subsample was selected for analysis of lipoprotein subfractions (~100 per study diet). Plasma samples were collected at baseline and after 24 months and stored at -80C to await analysis. Whole plasma was fractionated first by apoC-III content and then by density (VLDL, IDL+LDL, HDL) to produce 6 subfractions: VLDL with apoC-III, VLDL without apoC-III, IDL+LDL with apoC-III, IDL+LDL without apoC-III, HDL with apoC-III, HDL without apoC-III. Apolipoprotein and lipid concentrations were measured in these subfractions. The primary aim was to determine whether macronutrient content of diets for weight loss influenced changes after weight loss in concentrations and compositions of the 6 lipoprotein subfractions. A secondary analysis determined the relation between amount of weight-loss and change in the lipoproteins, adjusted for baseline BMI, age, race, and sex. Results: On average, the study population had lost 5% of their body weight at 2 years regardless of randomized diet group. Changes in lipoprotein subfractions from baseline to 2 years were similar among the 4 diet groups. Multiple regression analysis determined that degree of weight loss significantly predicted reductions in apoC-III in VLDL, LDL and HDL. For example, a 5% weight loss corresponded to reductions in apoC-III in VLDL of 14% (95% CI: 8.0%, 19.8%), LDL of 5.5% (0.3%, 8.6%), and HDL of 2.2% (0.1%, 4.4%). Weight loss notably predicted a decrease in the apoB concentration of LDL with apoC-III. The concentration of LDL with apoC-III was the strongest predictor of CVD in several cohorts. In contrast, weight loss predicted increases in apoE in VLDL and LDL. ApoE increases the clearance from plasma of VLDL and LDL and reduces the formation of LDL from VLDL. Conclusion: Weight loss achieved through healthful diets reduces apoC-III and atherogenic LDL with apoC-III but increases apoE in apoB-lipoproteins regardless of macronutrient emphasis. These effects on lipoprotein subfractions represent a novel mechanism by which weight loss may reduce cardiovascular disease risk.
Case 36-1963
Authors: Langdon Parsons, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of CaseA fifty-seven-year-old woman was admitted to the hospital because of pain in the groin.The patient's health had always been good, although she had been bothered for many years by distention of the abdomen. Three weeks before entry she experienced the onset of pain in the left lower quadrant of the abdomen and groin; the pain was sharp, intermittent and shooting in character and was not accompanied by numbness or leg weakness. Her physician informed her after an x-ray examination that she had a calcified tumor in the abdomen.The menstrual periods had been normal, and the . . .
An automated practice-based intervention for case management of abnormal mammograms
Authors: M. M. Eberl, C. H. Fox, G. Broffman, J. Pomerantz, J. Serghany, M. Reinhardt, N. Watroba, S. B. Edge
Journal: Journal of Clinical Oncology (2007)

6563 Background: Failure to obtain follow-up (f/u) of abnormal mammograms may delay cancer diagnosis and impact outcome; studies show up to 20% of women do not get recommended f/u. Our group previously established that administrative claims linked to medical records accurately identify care for management of abnormal mammograms. We are testing a case management system linking claims data to mammogram information to assist physicians in assuring appropriate f/u for abnormal mammograms. Methods: Electronic medical records in a staff model practice affiliated with a single payer are scanned to identify the BI-RADS code for all mammograms. The practice performs about 8,000 mammograms with about 500 abnormal mammograms annually. Physicians are notified of each abnormal mammogram and provided with a standardized care pathway for management. For each BI-RADS 0, 3, 4 or 5 mammogram, claims are searched for f/u breast procedures (imaging, biopsy, surgery). If recommended f/u (additional imaging for BI-RADS 0, biopsy by 2 months for BI-RADS 4 and 5, f/u imaging by 8 months for BI-RADS 3) is not observed, the ordering physician is alerted. Results: From 01/01/2001 to 12/31/2003, we observed that among women eligible for f/u, 189 (16%) did not receive BI-RADS recommended f/u care. In the prospective intervention from 1/1/06 - 6/30/06, 166 BI-RADS 0, 21 BI-RADS 4, and 3 BI-RADS 5 mammograms had 98.2%, 76.2%, and 100% appropriate f/u, respectively. From the alerts, all but one patient who refused biopsy received appropriate care. Conclusions: A practice intervention utilizing BI- RADS data linked to claims accurately identified missed f/u in a time frame when appropriate care can be delivered. This practice-based intervention has potential to improve the management of other cancers and chronic diseases. This intervention is being expanded on a community wide level. No significant financial relationships to disclose.
Effect of Reducing Agents and Oxygen on Plating Efficiency of Some Mammalian Cells in Culture
Authors: William G. Taylor, Katherine K. Sanford, Alan Richter, Miriam L. Hursey, Virginia J. Evans
Journal: JNCI Journal of the National Cancer Institute (1974)

In previous studies on factors influencing clonal growth in vitro, a gas phase containing 1% O2 , compared with atmospheric O2 (20%), enhanced plating efficiency (PE). To evaluate whether the lowered PE at 20% O2 could be alleviated by reducing agents, cysteine or thioglycolate was added to the plating medium. A low concentration of cysteine·HCI·H2O (1 mg/100 ml) slightly enhanced clonal growth but was toxic at higher concentrations. With 1% O2 and controlled pH, this cytotoxicity was reduced. In a second culture system widely used for quantitative chemical carcinogenesis in vitro, sodium thioglycolate failed to enhance PEa However, in this system, 1% O2 compared with atmospheric O2 significantly increased the PE of control and benzo[a]pyrene-treated hamster embryo cells plated on an irradiated feeder layer. We conclude that the cytotoxicity or clonal growth inhibition produced by atmospheric O2 cannot be alleviated by addition of either reducing agent to the plating medium.
A Phase 1 Study of Necitumumab (Anti-Egfr Monoclonal Antibody) in Japanese Patients with Advanced Solid Tumors
Authors: Hiroshi Nokihara, Noboru Yamamoto, Yosuke Tamura, Yuko Tanabe, Kazunori Honda, Hajime Asahina, Sotaro Enatu, Raffael Kurek, Yasuhide Yamada, Tomohide Tamura
Journal: Annals of Oncology (2014)
Mitochondrial Metabolism in Aging Heart
Authors: Edward J. Lesnefsky, Qun Chen, Charles L. Hoppel
Journal: Circulation Research (2016)

Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area, there is ≈50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction.