tbuckley/cabot-search huggingface dataset:
NMR studies of cisplatin and oxaliplatin 1,2-d(GG) intrastrand cross-links and undamaged DNA in the AGG sequence context
Authors: Yibing Wu, Jody Havener, Sharon Campbell, Stephen G. Chaney
Journal: Cancer Research (2004)

1894  Oxaliplatin (OX), a second-generation platinum drug recently approved by the FDA for the treatment of colorectal cancer, differs from cisplatin (CP) by addition of a cyclohexane ring to the amines of CP to form a diaminocyclohexane (DACH) ring. We have recently determined the three-dimensional solution structure of the OX-GG adduct in the AGG sequence context by 2D NMR and have reported (Proc. AACR, 44: 83, 2003) that the structure of the OX-GG adduct was different from all previous solution structures of the CP-GG adduct. However, the previous solution structures of the CP-GG adduct were in the CGG and TGG sequence contexts, and Pt-GG adducts in the AGG sequence context are known to be more mutagenic than in other sequence contexts. Thus, it was not clear whether the differences observed were due to differences between OX-GG and CP-GG adducts or to differences in sequence context. Therefore, we have also characterized by 2D NMR undamaged DNA and DNA with the CP-GG adduct in the same d(CCTCAGGCCTCC)•d(GGAGGCCTGAGG) dodecamer duplex used for the OX-GG adduct. Sequential proton assignments are complete for both the CP-GG and undamaged DNA duplexes and 85-90% of the protons have been assigned for the CP-GG adduct. Several significant differences are observed between the OX-GG adduct and CP-GG adduct, and between the CP-GG adduct in the AGG sequence context and the data reported for CP-GG adducts in other sequence contexts. From the temperature dependence of the H1-imino peak volume, it can be concluded that the G6 H1 exchanges with water much more rapidly than the G7 H1 for both the CP-GG and OX-GG adducts, and that both the G6 H1 and G7 H1 protons exchange with water more rapidly for the OX-GG adduct than the CP-GG adduct. A number of chemical shift differences are observed for protons of the central four base pairs between the CP-GG and OX-GG adducts and between our CP-GG adduct and CP-GG adducts in other sequence contexts. For the CP-GG adduct strong H1-H2′ and weak H1′-H2“ DQF-COSY cross peaks were observed for both A5 and G6, consistent with the sugar in the N conformation for both nucleotides and consistent with the reported CP-GG structures in other sequence contexts. In contrast, N sugar pucker was observed for only the G6 sugar in the OX-GG structure. Finally, significant differences were observed between CP-GG and OX-GG adducts in the 1H-31P Hetcor spectra. These data suggest that the conformation of Pt-GG adducts is likely to be influenced by both the nature of the adduct (CP vs OX) and the sequence context. The possible significance of these differences for the cytotoxicity and mutagenicity of CP and OX will be discussed. (Supported by NIH grant CA84480).
LesionTracker: Extensible Open-Source Zero-Footprint Web Viewer for Cancer Imaging Research and Clinical Trials
Authors: Trinity Urban, Erik Ziegler, Rob Lewis, Chris Hafey, Cheryl Sadow, Annick D. Van den Abbeele, Gordon J. Harris
Journal: Cancer Research (2017)

Abstract Oncology clinical trials have become increasingly dependent upon image-based surrogate endpoints for determining patient eligibility and treatment efficacy. As therapeutics have evolved and multiplied in number, the tumor metrics criteria used to characterize therapeutic response have become progressively more varied and complex. The growing intricacies of image-based response evaluation, together with rising expectations for rapid and consistent results reporting, make it difficult for site radiologists to adequately address local and multicenter imaging demands. These challenges demonstrate the need for advanced cancer imaging informatics tools that can help ensure protocol-compliant image evaluation while simultaneously promoting reviewer efficiency. LesionTracker is a quantitative imaging package optimized for oncology clinical trial workflows. The goal of the project is to create an open source zero-footprint viewer for image analysis that is designed to be extensible as well as capable of being integrated into third-party systems for advanced imaging tools and clinical trials informatics platforms. Cancer Res; 77(21); e119–22. ©2017 AACR.
Abstract 14271: Patiromer Controls Hyperkalemia in Resistant Hypertensive Patients on RAASi, With Diabetic Kidney Disease
Authors: Murray Epstein, Martha Mayo, Dahlia Garza, Yuri Stasiv, Rezi Zawadski, Lance Berman, Dan Wilson, George Bakris
Journal: Circulation (2015)

Introduction: Emerging treatments for hyperkalemia (HK) may have favorable effects on the risk:benefit ratio for pts with HTN and diabetic kidney disease (DKD) treated with RAASi. HK develops in ~7-14% of pts with HTN and DKD, which can limit RAASi dosing and potential cardio-renal benefit. Hypothesis: This post hoc analysis from the 52-wk AMETHYST-DN study examined the K + -lowering effect of patiromer, an investigational potassium binding polymer, in resistant HTN (RTN) pts with HK and DKD. Methods: Hypertensive pts with mild (&gt;5.0-5.5 mEq/L) and moderate (&gt;5.5-&lt;6.0 mEq/L) HK and DKD on RAASi were treated with patiromer in an 8-wk treatment initiation phase (TIP), followed by a 44-wk long-term maintenance phase (LTMP). Safety and efficacy were assessed/analyzed in a RTN cohort (defined at baseline [BL], as a SBP &gt;140 mmHg on ≥4 classes of antihypertensive medication including a diuretic). Results: In AMETHYST-DN, 79/306 pts (67+7 yrs, 51% male) - 64 with mild HK, mean (±SEM) s-K + 5.18 (0.03) mEq/l, and 15 with moderate HK s-K + 5.77 (0.04) mEq/l - had RTN on RAASI. Mean (±SD) HR and SBP/DBP were 73 (10) bpm and 156 (10) mmHg / 83 (12) mmHg at BL. At BL stage ≥3b CKD was present in 51/79 pts (65%). Significant reductions in s-K + from BL occurred at each time point over the 52 wks /end of therapy (ET) (Figure). Investigators could add/modify non-RAASi antihypertensive medications, without known effect on s-K + , for BP control. Similar to the BP changes observed in the intent-to-treat population, at ET the change in mean (±SD) SBP/DBP was -18 (17) mmHg/ -9.0 (13) mmHg in the RTN group. Mean (±SD) change in eGFR from BL was –2.1 (12) mL/min/1.73m 2 . A total of 5/79 withdrew from study due to a patiromer related AE (hypokalemia 3, constipation 2). Doubling of serum Cr occurred in 7 pts; 1 death occurred during LTMP. Conclusions: Patiromer effectively controlled HK throughout a 52-wk period in a high-risk cohort of RTN pts, which enabled these pts to continue to use RAASi to control BP.
La mortalidad en Portugal asociada a la ola de calor de agosto de 2003 : estimación preliminar del efecto, usando un método rápido
Authors: P J Nogueira, J M Falcão, M T Contreiras, E Paixão, J Brandão, I Batista
Journal: Eurosurveillance (2005)

Durante las dos primeras semanas de agosto de 2003, Portugal fue afectado por una intensa ola de calor. 
Tras la identificacion en ese pais de la influencia de las olas de calor sobre la mortalidad en 1981 y 1991 (con un exceso estimado aproximado de 1.900 y 1.000 defunciones, respectivamente), el Observatorio Nacional de Saude (ONSA) - Instituto Nacional de Saude Dr. Ricardo Jorge, en collaboracion con Vigilância Previsao e Informacao - Instituto de Meteorologia, creo un sistema de vigilancia llamado ICARO, que funciona desde 1999. El sistema identifica las olas de calor con efectos potenciales sobre la mortalidad [1].
Antes del final de la ola de calor de 2003, el ONSA habia publicado una estimacion preliminar de sus efectos sobre la mortalidad. Los resultados, basados en el numero de defunciones diarias entre el 1 de junio y el 12 de agosto de 2003, fueron presentados en cuatro dias laborables. Los datos fueron recogidos de los 31 Registros nacionales civiles, que cubren las capitales regionales de las 18 regiones de Portugal continental y representan el 40% de la mortalidad en el continente. 
El numero de defunciones registrado durante el periodo del 30 julio al 12 agosto se comparo con los registrados durante tres periodos de comparacion (de 2003) : 1-14 julio, 1-28 julio, y 15-28 julio. Para el periodo entre el 15 y el 28 de julio, el mas parecido a la ola de calor por su duracion y sus caracteristicas, se estimo una tasa de mortalidad un 37,7% superior al valor esperado en condiciones climaticas normales. A partir de este valor, se obtuvo una estimacion de 1.316 defunciones en exceso para Portugal continental. El principal objetivo de este articulo es presentar el metodo utilizado para la identificacion y evaluacion del exceso de mortalidad durante la ola de calor del verano de 2003.
Risk Factors Associated with Asthma Development and Control in Children. Mouse Infestation, Antipyretics, Respiratory Viruses, and Allergic Sensitization
Authors: Mark Wurth, Christina M. Papantonakis, Rebekah J. Nevel, Caroline S. Thomas, Andrew G. Sokolow, Paul E. Moore, Christian Rosas-Salazar
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
TCT-730 Five-year risk of target lesion revascularization in patients with and without an acute coronary syndrome treated with drug-eluting stents: a pooled analysis of individual participant data from three randomized SORT OUT trials
Authors: Manan Pareek, Evald Christiansen, Lisette Okkels Jensen, Bent Raungaard, Steen Dalby Kristensen, Svend Eggert Jensen, Henrik Hansen, Anders Junker, Karsten Veien, Morten Madsen, Michael Maeng
Journal: Journal of the American College of Cardiology (2017)
Brote de norovirus detectado en un hotel del oeste de Irlanda, 2006
Authors: A Michel, R FitzGerald, D Whyte, A Fitzgerald, E Beggan, N O’Connell, T Greally
Journal: Eurosurveillance (2007)

En Octubre de 2006 se desencadeno un brote de gastroenteritis (nauseas, vomitos y diarrea) entre los invitados a una boda, el personal y otros huespedes de un hotel del occidente de Irlanda.
New presentation of autoimmune hepatitis with erythema multiforme
Authors: Tatyana Kushner, Kanade Shinkai, Lindy Fox, David Ying, Andrew Gross, Dana Balitzer, Ryan Gill, Danielle Brandman
Journal: Hepatology (2017)

Kushner, Tatyana; Shinkai, Kanade; Fox, Lindy; Ying, David; Gross, Andrew; Balitzer, Dana; Gill, Ryan; Brandman, Danielle Author Information
Multiplex immunohistochemical characterization of Aurora A and Aurora B in breast, ovarian, non-small cell lung, and colon cancer
Authors: Christopher Kerfoot, Sherif Girees, Lisa Dauffenbach
Journal: Cancer Research (2007)

4361   Aurora A and Aurora B are frequently over-expressed in a variety of cancers, and their inhibition has been demonstrated to cause selective apoptosis of tumor cells. Many investigation drugs target one or both of these molecules, and clinical trials are in progress to determine efficacy. The present study used an Aurora A / Aurora B / ki67 multiplex immunohistochemistry (IHC) assay to study expression of the Auroras in breast, ovarian, non-small cell lung, and colon cancer in addition to normal tissues. Unsynchronized and nocodazole-treated HeLa cells were analyzed to demonstrate assay specificity, and increased expression of Aurora A and Aurora B was observed in nocodazole treated cells. Stained samples of cancer and normal tissue were imaged using multispectral imaging, and quantitative grayscale images for each analyte were created by spectral unmixing. The quantitative grayscale images were analyzed using image analysis software to determine the overall expression levels of Aurora A and Aurora B expression and the relationship between the two was evaluated using a 2-D scatterplot. The relationship between Aurora staining and ki67 was also evaluated. Evaluation and classification of cancers by multiplex Aurora analysis may provide critical insight into factors that predict response to Aurora kinase inhibitors in the clinic.
Clinical Outcomes and Cost-Effectiveness of Fractional Flow Reserve–Guided Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease
Authors: William F. Fearon, Takeshi Nishi, Bernard De Bruyne, Derek B. Boothroyd, Emanuele Barbato, Pim Tonino, Peter Jüni, Nico H.J. Pijls, Mark A. Hlatky
Journal: Circulation (2017)

Background: Previous studies found that percutaneous coronary intervention (PCI) does not improve outcome compared with medical therapy (MT) in patients with stable coronary artery disease, but PCI was guided by angiography alone. FAME 2 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) compared PCI guided by fractional flow reserve with best MT in patients with stable coronary artery disease to assess clinical outcomes and cost-effectiveness. Methods: A total of 888 patients with stable single-vessel or multivessel coronary artery disease with reduced fractional flow reserve were randomly assigned to PCI plus MT (n=447) or MT alone (n=441). Major adverse cardiac events included death, myocardial infarction, and urgent revascularization. Costs were calculated on the basis of resource use and Medicare reimbursement rates. Changes in quality-adjusted life-years were assessed with utilities determined by the European Quality of Life–5 Dimensions health survey at baseline and over follow-up. Results: Major adverse cardiac events at 3 years were significantly lower in the PCI group compared with the MT group (10.1% versus 22.0%; P &lt;0.001), primarily as a result of a lower rate of urgent revascularization (4.3% versus 17.2%; P &lt;0.001). Death and myocardial infarction were numerically lower in the PCI group (8.3% versus 10.4%; P =0.28). Angina was significantly less severe in the PCI group at all follow-up points to 3 years. Mean initial costs were higher in the PCI group ($9944 versus $4440; P &lt;0.001) but by 3 years were similar between the 2 groups ($16 792 versus $16 737; P =0.94). The incremental cost-effectiveness ratio for PCI compared with MT was $17 300 per quality-adjusted life-year at 2 years and $1600 per quality-adjusted life-year at 3 years. The above findings were robust in sensitivity analyses. ConclusionS: PCI of lesions with reduced fractional flow reserve improves long-term outcome and is economically attractive compared with MT alone in patients with stable coronary artery disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01132495.
Lay Workers Can Ease Distress in Women Exposed to Violence
Authors: Anita Slomski
Journal: JAMA (2017)

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Nova variante da doença de Creutzfeldt-Jakob
Authors: D Dormont
Journal: Eurosurveillance (2000)

Trabalhos de patologia experimental efectuados ao longo de 10 anos indicam que as propriedades biologicas do agente da BSE, responsavel pela nova variante da doenca de Creutzfeldt-Jakob (nvDCJ), sao especificas. Em contraste com a situacao observada na outra forma da DCJ, a distribuicao do agente responsavel pela nvDCJ e em grande parte periferica nos humanos. Isto exige uma reconsideracao sobre o grau de seguranca dos transplantes, dos farmacos de origem humana ou bovina e das transfusoes.
Can we increase response rate (RR) and overall survival (OS) by individualizing chemotherapy in ovarian cancer (OC): The role of a new chemotherapy (CT) induced apoptosis assay.
Authors: E. M. Salom, M. Penalver, H. D. Homesley, C. A. Presant, J. Rutledge, M. O. Burrell, A. P. Garrett, A. Hallquist, M. Perree
Journal: Journal of Clinical Oncology (2010)

5112 Background: In order to develop an assay to improve OS of OC pts, we tested pt tumor cells (TC) using a novel CT- induced in vitro apoptotic assay (the Microculture Kinetic [MiCK] assay). This was a prospective blinded trial in which physicians selected CT without knowledge of MiCK assay results. Methods: TC obtained at surgery were prepared and cultured with drugs as previously described (Lab Invest 74: 557, 1996). TC apoptosis from single drugs or combination regimens was measured over 48 hours. Assay results were compared to OS and RR following CT. The assay results were measured as kinetic units of apoptosis (KU) with > or = 1.7 KU defined highly active vs less active < 1.7 KU. The best CT was defined as apoptosis > 0.57 KU (> 1 measurement s.d.) higher than other drugs. Results: A total 128 pts were evaluable for MiCK results. Combination paclitaxel (Pac) + carboplatin (C) gave significantly more apoptosis 2.6 KU vs. single agent Pac 1.8 KU or C 1.4 KU (p < 0.0001). However, single drug Pac or C was more effective than Pac+C in 28% and was equal to Pac+C in 9% of pts. In 46% of pts, another drug or combination produced more apoptosis compared to Pac+C. When comparing CT for all stages, OS was significantly better at 24 months in 92% pts who received best CT vs. only 76% in pts who received a non-best assay predicted CT (p = 0.01). There was a significantly higher overall RR 82% in pts who received the best CT in the assay vs. 54% in pts who received a non-best assay predicted CT (p = 0.04). In stage 3 or 4 (54/90) OC pts treated with highly active CT by assay had a significantly increased OS (94% alive at 24 mo) compared those with less active CT (77% alive; p = 0.02). The hazard ratio for death in pts receiving highly active CT was 0.17 (95% CI 0.03- 0.92). The CR, PR, SD, and nonrelapse rate was 85% for pts with highly active CT, compared to 57% for those pts receiving less active CT (p = 0.03). Conclusions: The drug induced apoptosis MiCK assay is useful in predicting which CT will result in increased OS and increased RR in this study. This assay can help oncologists to select the best CT for individual pts. The assay may help develop new CT regimens and select responsive pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration DiaTech Oncology DiaTech Oncology DiaTech Oncology DiaTech Oncology
T-cell–mediated immune response to pneumococcal conjugate vaccine (PCV-13) and tetanus toxoid vaccine in patients with moderate-to-severe psoriasis during tofacitinib treatment
Authors: Kevin L. Winthrop, Neil Korman, William Abramovits, Scott T. Rottinghaus, Huaming Tan, Annie Gardner, Geoffrey Mukwaya, Mandeep Kaur, Hernan Valdez
Journal: Journal of the American Academy of Dermatology (2018)
Subjective Complaints as the Main Reason for Biosimilar Discontinuation After Open‐Label Transition From Reference Infliximab to Biosimilar Infliximab
Authors: Lieke Tweehuysen, Bart J. F. van den Bemt, Iris L. van Ingen, Alphons J. L. de Jong, Willemijn H. van der Laan, Frank H. J. van den Hoogen, Alfons A. den Broeder
Journal: Arthritis & Rheumatology (2017)

Objective To evaluate drug survival, effectiveness, pharmacokinetics, immunogenicity, and safety in daily practice after transitioning treatment from original reference infliximab (Remicade [ REM ]) to a biosimilar infliximab ( CT ‐P13 [Remsima; Inflectra]) in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. Methods Of the initial 222 REM ‐treated patients, 192 agreed to transition to CT ‐P13 and were included in this multicenter prospective cohort study. Changes in the Disease Activity Score in 28 joints using the C‐reactive protein level ( DAS 28‐ CRP ) and the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) and changes in the CRP levels, infliximab trough levels, and anti‐infliximab antibody levels were assessed after 6 months, and adverse events ( AE s) were documented. Drug survival and prognostic factors were analyzed using Kaplan‐Meier and Cox regression analyses. Results During 6 months follow‐up, 24% of the patients (n = 47) discontinued CT ‐P13. Thirty‐seven patients restarted REM , 7 switched to another biologic drug, and 3 continued without a biologic drug. The DAS 28‐ CRP remained stable from baseline to month 6, with a mean ± SD score of 2.2 ± 0.9 at baseline to 2.2 ± 0.8 at 6 months (difference of 0.0 [95% confidence interval (95% CI ) –0.1, 0.2]). The BASDAI increased from a mean ± SD of 3.8 ± 2.0 at baseline to 4.3 ± 2.1 at 6 months (difference of +0.5 [95% CI 0.1, 0.9]). The CRP levels, infliximab trough levels, and anti‐infliximab antibody levels did not change. Just prior to CT ‐P13 discontinuation, the DAS 28‐ CRP components tender joint count and patient's global assessment of disease activity, as well as the BASDAI were increased compared to baseline. The most frequently reported AE s were arthralgia, fatigue, pruritus, and myalgia. A shorter REM infusion interval (hazard ratio: 0.77 [95% CI 0.62, 0.95]) at baseline was predictive of discontinuing CT ‐P13. Conclusion In our cohort, one‐fourth of patients discontinued CT ‐P13 during 6 months of follow‐up, mainly due to an increase in the subjective features of the tender joint count and the patient's global assessment of disease activity and/or subjective AE s, possibly explained by nocebo effects and/or incorrect causal attribution effects.
Anaesthetist is jailed after stealing codeine from hospital where he no longer worked
Authors: Clare Dyer
Journal: BMJ (2017)

A doctor who repeatedly used his old hospital pass after his employment ended to enter the hospital and steal codeine tablets has been jailed for eight months.

Paul Wilkinson, 30, worked for two years in anaesthetics at Aintree University Hospital in Liverpool, but when his contract ended he retained his pass. Over an eight month period he used it to enter the hospital on 75 occasions, wearing medical scrubs and stealing 2558 tablets worth £3360 (€3770; $4430) to feed his painkiller addiction.

Sentencing him at Liverpool Crown Court, Judge …