tbuckley/cabot-search huggingface dataset:
Ectopia Lentis in Marfan's Syndrome
Authors: David R Lally, Julia Monsonego
Journal: New England Journal of Medicine (2014)

A 27-year-old woman with Marfan's syndrome presented with worsening vision and glare in each eye. Superotemporal partial subluxation of the lens was noted in each eye. Close inspection revealed a decrease in the number of zonules, with widened spaces between zonules.
Pulsed ATRA as single therapy restores long-term remission in PML-RARα-positive acute promyelocytic leukemia patients: real time quantification of minimal residual disease. A pilot study
Authors: G Visani, S Buonamici, M Malagola, A Isidori, PP Piccaluga, G Martinelli, E Ottaviani, T Grafone, M Baccarani, S Tura
Journal: Leukemia (2001)
Abstract 675: Effects of PBN and OKN007 in rodent glioma models assessed by 1H MR spectroscopy
Authors: Ting He, Sabrina Doblas, Debra Saunders, Rebba Casteel, Robert A. Floyd, Rheal A. Towner
Journal: Cancer Research (2011)

Abstract Gliomas are the most common and lethal primary brain tumors in the adult, with a median survival time of 12 to 15 months for grade IV gliomas, glioblastoma multiforme. PBN and OKN007 are nitrones which have demonstrated beneficial effects in many aging diseases. In this study, we evaluated the anti-tumor effects of PBN or OKN007 in several rodent glioma models (C6, RG2, and GL261) by assessing metabolite alterations with magnetic resonance spectroscopy (MRS). PBN or OKN007 was administered in drinking water prior to or post tumor formation. MRI and short echo time, single-voxel point-resolved spectroscopy (PRESS) were obtained to assess tumor morphology and metabolites, respectively, following therapy. Major metabolite ratios (Choline, N-acetyl aspartate (NAA), Lipid (methylene), and Lipid (methyl), all compared to Creatine) were assessed. Nitrones induced tumor metabolism changes that resulted in restoring major metabolite ratios close to their normal levels, in the glioma regression phase. Nitrones treatment decreased the Lipid (methylene) to Creatine ratio significantly, which can be a useful marker for evaluation of the efficacy of the treatments, and was found to be related with the reduction of necrosis. OKN007 was more effective than PBN when administered post-tumor formation in the C6 glioma model. OKN007 was able to inhibit angiogenic factors (VEGF, bFGF and HGF) and induce apoptosis (indicated by an increase of the apoptotic marker m30) in C6 gliomas, which might be potential mechanisms that are involved in the anti-glioma effects. In conclusion, OKN007 and PBN are effective in inhibiting the growth of several experimental gliomas and may be considered as potential therapeutics for a clinical trial in human gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 675. doi:10.1158/1538-7445.AM2011-675
Abstract 5243: The novel calcium-dependent direct binding of S100B to p90 ribosomal S6 kinase (RSK) decreases MAP kinase-mediated RSK activation in malignant melanoma.
Authors: Adam D. Pierce, Kira G. Hartman, David Weber
Journal: Cancer Research (2013)

Abstract S100B is an effective and extensively used prognostic marker for melanoma, with increasing serum S100B being predictive of disease stage, increased recurrence, and low overall patient survival. Establishing the mechanism by which S100B alters cell signaling provides insight into how it may facilitate the progression of melanoma and aid in developing new pharmacological drugs to inhibit cancer advancement. To evaluate specific roles for S100B in malignant melanoma, our S100B knock-down and over-expression studies established a correlation between S100B expression and cell viability. ERK phosphorylation was also found to correlate with S100B levels. We have discovered RSK, a downstream ERK target, as a novel binding partner of S100B. RSK is known to regulate MAPK signaling in melanoma but the mechanism is unclear. We observed an inverse relationship between activated and phosphorylated RSK and S100B levels. We used a Ca2+-binding mutant of S100B (E31A + E72A) to demonstrate that the S100B-RSK interaction was calcium-dependent. Pull-down experiments revealed the C-terminal domain of RSK to be necessary for S100B binding. In vitro, S100B was found to reduce ERK-dependent phosphorylation of RSK at Thr573. Our cellular fractionation and immuno-fluorescence studies showed that S100B protein prevented nuclear localization of phosphorylated RSK. These data are consistent with a mechanism in which elevated S100B binds directly to RSK in a calcium-dependent manner, preventing ERK-mediated phosphorylation of RSK and inhibiting RSK localization to the nucleus. We have identified the S100B-RSK interaction as a novel drug target in melanoma cells. We are currently screening compounds for inhibitors of the S100B-RSK interaction. Citation Format: Adam D. Pierce, Kira G. Hartman, David Weber. The novel calcium-dependent direct binding of S100B to p90 ribosomal S6 kinase (RSK) decreases MAP kinase-mediated RSK activation in malignant melanoma. [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 5243. doi:10.1158/1538-7445.AM2013-5243
Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program
Authors: Bradley A. Maron, Edward Hess, Thomas M. Maddox, Alexander R. Opotowsky, Ryan J. Tedford, Tim Lahm, Karen E. Joynt, Daniel J. Kass, Thomas Stephens, Maggie A. Stanislawski, Erik R. Swenson, Ronald H. Goldstein, Jane A. Leopold, Roham T. Zamanian, Jean M. Elwing, Mary E. Plomondon, Gary K. Grunwald, Anna E. Barón, John S. Rumsfeld, Gaurav Choudhary
Journal: Circulation (2016)

Background— Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP &lt;25 mm Hg to clinical outcome is unknown. Methods and Results— We analyzed retrospectively all US veterans undergoing right heart catheterization (2007–2012) in the Veterans Affairs healthcare system (n=21 727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004–1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (≤18 mm Hg; n=4 207); (2) borderline PH (19–24 mm Hg; n=5 030); and (3) PH (≥25 mm Hg; n=12 490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12–1.36; P &lt;0.0001) and PH (HR=2.16; 95% CI, 1.96–2.38; P &lt;0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01–1.12; P =0.0149) and PH (HR=1.15; 95% CI, 1.09–1.22; P &lt;0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure &gt;15 mm Hg; (2) pulmonary vascular resistance ≥3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. Conclusions— These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH.
The One Health approach for the management of an imported case of rabies in mainland Spain in 2013
Authors: A C Pérez de Diego, M Vigo, J Monsalve, A Escudero
Journal: Eurosurveillance (2015)

After more than 30 years without any reported cases of rabies in terrestrial carnivores in mainland Spain, an imported case was detected in June 2013 in Toledo. Although the infected dog was moved across different locations and had contact with humans and dogs, the incident was controlled within a few days. An epidemiological investigation was performed and rabies-free status in terrestrial carnivores in mainland Spain was restored six months after the incident. Key to the successful management of this case were the previous vaccination of susceptible animals in the affected area before the case was detected, the collaboration of different authorities in decision making, and the application of control measures according to national and international regulations and to the One Health concept.
Should the Age of Breast Cancer Screening for Ethnic Minorities Be Reduced?
Authors: S. Soumian, T. Sircar, L. Whisker, J. Skillman, N. Abbott, H. Winter, V. Kaur, O. Kearins, G. Lawrence
Journal: Cancer Research (2009)

Abstract IntroductionThe National Health Service Breast Screening Programme (NHSBSP) offers breast screening every three years for all women aged 50 and over in the United Kingdom (UK). Women aged between 50 and 70 are routinely invited. The NHSBSP will extend the age range of women invited for breast screening from ages 47 to 73 in the future. However, the ideal age for screening should take into consideration the relative risk of the population. The UK has a significant population of ethnic minority groups, mainly Asian and Afro-Caribbean, comprising of about 8% of the total population. The ethnic minority groups have remained geographically concentrated in specific regions especially London and West Midlands, where they comprise 30% and 14% of the population respectively. It has been reported that ethnic minorities present with relatively advanced breast cancer at a younger age. These groups could potentially benefit from early screening. We wanted to test this hypothesis by assessing the age and route of presentation of breast cancer across ethnic groups in the West Midlands region.MethodsThe West Midlands Cancer Intelligence Unit (WMCIU), a population based registry, collects prospective data on breast cancer diagnosed and treated in this region. Data on patients treated for breast cancer from 2001 to 2007 was obtained from the WMCIU. The age and route of presentation (screening or symptomatic) of Asian, Afro-Caribbean and Caucasian patients were analysed and compared.Results.A total of 27,444 female patients were diagnosed during this period. Data regarding ethnicity was available for 18,941 Caucasians, 528 Asians and 274 Afro-Caribbean's. Diagnosis through screening was 37%, 26% and 29% for Asian, Afro-Caribbean and the Caucasian population respectively. In the symptomatic group, 26.5% of Asians and 35% of Afro-Caribbeans presented below the age of 47 years compared to 13% of the Caucasian population. Furthermore, 13.5% of Asians, 16.5%of Afro-Caribbeans and 5.9% of Caucasians presented at or below the age of 40 years.ConclusionA significant percentage of breast cancers diagnosed within ethnic groups will still be missed despite revising the screening age to 47 years. Unless the participation of ethnic groups in screening is targeted, the benefits (detecting disease at an earlier stage and potentially reduced mortality) will be lost. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4008.
Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction
Authors: Glenn N. Levine, John A. Bittl
Journal: JAMA Cardiology (2016)

This Clinical Guidelines Synopsis describes the 2015 update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction.
Abstract 2733: Molecular markers for predicting progression of pure ductal carcinoma in situ of the breast
Authors: Carolina Sens Abuázar, Elisa Napolitano e Ferreira, Cynthia Aparecida Bueno de Toledo, Fernando Augusto Soares, Rafael Malagoli Rocha, Dirce Maria Carraro
Journal: Cancer Research (2010)

Abstract INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of tumors which has an uncertain and poorly understood evolution. For this reason, the identification of molecular factors necessary for progression to invasive disease is one of the main concerns of the scientific community. We previously identified, by a microarray assay, a group of genes potentially involved in progression of DCIS, which are differentially expressed between pure DCIS and in situ component of lesions with co-existing invasive ductal carcinoma (DCIS-IDC). For this experiment, only the in situ components of pure DCIS and DCIS-IDC lesions were isolated using laser microdissection technique. AIM: Seek novel molecular markers to predict invasiveness potential in a DCIS group of breast carcinomas by qRT-PCR and Immunohistochemistry (IHC). METHODS: For qRT-PCR, 18 genes were selected, for which there were available antibodies. The qRT-PCR reactions were performed in ABIPrism 7700 Sequence Detection System (Applied Biosystems, Foster City, CA, USA) and the criterion of gene expression difference was equal or greater than 2-fold change. IHC was performed in a tissue microarray (TMA), using a biotin-free polymeric system for visualization (Flex+, DAKOTM). The distribution of IHC markers was analyzed using the Chi-square test for trend or Fisher's exact test. RESULTS: The expression of 4 genes (ADFP, ARHGAP19, ANAPC13 and CLTCL1) was confirmed by qRT-PCR, in the initial sample set used in the microarray experiment, presenting higher expression in the pure DCIS group. IHC was conducted to evaluate the corresponding proteins, using an independent group of 47 pure DCIS and 35 DCIS-IDC samples arrayed in TMA. Two genes, ANAPC13 (p=0.0379) and CLCTL1 (p=0.0471), confirmed the expression at protein level, showing significant higher cytoplasm staining in the pure DCIS group. CONCLUSION: ANAPC13 and CLTCL1 may be involved in progression of DCIS, being good candidates for predicting invasion of pure DCIS. Financial support: CEPID and FAPESP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2733.
THU0186 Cardiac valve abnormalities in systemic lupus erythematosus (SLE) patients detected by transthoracic and transesophageal echocardiography (TTE and TEE)
Authors: L.S. Kholopov, O.I. Dyadyk, A.E. Bagriy, V.O. Gajdukov, O.V. Samojlova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SLE can affect all components of the heart, namely the pericardium, conduction system, myocardium, valves, and coronary arteries. Valvular heart disease is one of the most typical and prognostically significant cardiac lesions in SLE. <h3>Objectives</h3> The aim of our study was to evaluate cardiac valve lesions in SLE pts using TEE in combination with TTE. <h3>Methods</h3> TTE and TEE were performed in 76 consecutive pts (13M:63F, mean age 28 yrs) using Philips HDI 5000 with 2.0-4.0 MHz transducer and EnVisor C with multiplan 5 MHz TEE transducer. <h3>Results</h3> Cardiac valve lesions were detected by TTE in 54 patients. TEE reveled additional information about valvular structure/function in 16 of those pts and detected valve abnormalities in new 13 pts. Combined TTE+TEE evaluated valve lesions in 67 (88.2%) pts. Valve structure abnormalities were represented as thickness/stiffness of valve leaflets in 44.7% (mitral – 31.6%, aortic – 21.1%, tricuspid – 9.2%); valve masses/vegetations (Libman-Sacks) in 35.5% (mitral – 18.4%, aortic – 14.5%, tricuspid – 2.6%). Moderate-to-severe mitral regurgitation was detected in 26.3% pts, aortic regurgitation – in 7.9%, tricuspid regurgitation – in 3.9%). Mitral stenosis was found in only 5.3% and in all cases it was combined with mitral regurgitation. <h3>Conclusions</h3> We found high prevalence of cardiac valve lesions in studied cohort of SLE pts. Those lesions were represented as wide variety of valve structure and function abnormalities. TEE appears to be accurate diagnostic tool in SLE valve lesions. <h3>References</h3> Leonard Wei-Ren Lan, Cheng-Ting Tsai and Charles Jia-Yin Hou. The Valvular Involvement of Lupus: Congestive Heart Failure Can Be The Presenting Feature of Systemic Lupus Erythematosus/Acta Cardiol Sin 2005;21:111-115. Fluture A, Chaudhari S, Frishman WH. Valvular heart disease and systemic lupus erythematosus: therapeutic implications/Heart Dis. 2003 Sep-Oct;5(5):349-53. Roldan CA, Qualls CR, Sopko KS, Sibbitt WL Jr. Transthoracic versus transesophageal echocardiography for detection of Libman-Sacks endocarditis: a randomized controlled study/J Rheumatol. 2008 Feb;35(2):224-9. <h3>Disclosure of Interest</h3> None Declared
Minsters use veto to stop publication of register of risks posed by NHS changes
Authors: C. Dyer
Journal: BMJ (2012)

The official assessment of the risks that the UK government is running by its far reaching shake up of the NHS will not be released to the public, after the cabinet approved a rare use of the ministerial veto to stop publication.

The veto by the health secretary for England, Andrew Lansley, brings to an end a 19 month campaign by the opposition Labour Party and medical bodies to force the Tory led coalition government to publish the transition risk register for the Health and Social Care Act.

Ministers have been ordered twice, by the information commissioner and the information rights tribunal …
RELATIONSHIP BETWEEN REDUCTION OF SYSTOLIC BLOOD PRESSURE AND ATRIAL FIBRILLATION BURDEN AFTER RENAL DENERVATION AND PULMONARY VEIN ISOLATION
Authors: Evgeny Pokushalov, Alexander Romanov, Demosthenes Katritsis, Artem Strelnikov, Sergey Artyomenko, Denis Losik, Vera Baranova, Alexander Karaskov, Jonathan Steinberg, Dejan Risteski
Journal: Journal of the American College of Cardiology (2015)
Abstract 983: A dual inhibitor of MDR-1 and ABCG2,elacridar, enhances cytotoxic effects of sunitinib on RCC cell lines.
Authors: Hiromi Sato, Sana Siddig, Rina Suzuki, Miaki Uzu, Sayumi Suzuki, Yuki Nomura, Yuko Sekine, Tomoya Uehara, Yasushi Arano, Koichi Ueno
Journal: Cancer Research (2013)

Abstract Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor (TKI) and currently approved for use in advanced renal cell carcinoma (RCC). It is really attractive drug for patients who cannot have surgical treatment. However, it is reported that TKI might be substrates of ATP-binding cassette (ABC) transporters, which are able to mediate the efflux of anti-tumor drugs from the tumor cells. In this study, we suggested that inhibition of MDR transporters by elacridar (dual inhibitor of MDR-1 and ABCG2) might overcome sunitinib resistance in experimental RCC. We used 786-O and Caki-1 RCC cell lines. The cells were treated with sunitinib alone, elacridar alone or the combination, then cytotoxicity was measured by the MTT cytotoxicity method. The expression of MDR-1 and ABCG2 mRNA and their protein were detected by real time RT-PCR or Western blotting. Additionally, P-gp function was analyzed by using 99mTc-MIBI. MCF-7 cells were used as negative control for P-gp functional assay. Our results showed that elacridar significantly enhanced sunitinib cytotoxicity in RCC cells. High P-gp expression was especially observed in 786-O, though that of ABCG2 was almost the same among cells. Additionally P-gp assay revealed that the protein would be active and elacridar blocked its function in 786-O, where the accumulation of the 99mTc-MIBI increased 7 folds compared to the control (non-treatment group). These findings suggest that sunitinib resistance is partly mediated by gene and protein expression of MDR transporters. Therefore combination with elacridar could reverse its resistance in MDR sensitive cancer cells, as it did in 786-O. Citation Format: Hiromi Sato, Sana Siddig, Rina Suzuki, Miaki Uzu, Sayumi Suzuki, Yuki Nomura, Yuko Sekine, Tomoya Uehara, Yasushi Arano, Koichi Ueno. A dual inhibitor of MDR-1 and ABCG2,elacridar, enhances cytotoxic effects of sunitinib on RCC cell lines. [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 983. doi:10.1158/1538-7445.AM2013-983
AB0797 Impairment of coronary microcirculation in patients with diffuse systemic sclerosis:
Authors: F. Atzeni, L. Gianturco, P. Sarzi-Puttini, C. Ricci, L. Tommasoni, V. De Gennaro Colonna, P. Ferrario, O. Epis, M. Turiel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> An association between systemic autoimmune diseases (SADs) and atherosclerosis has been described in many connective tissue diseases, and is known to lead to increased cardiovascular (CV) morbidity and mortality. Systemic sclerosis (SSc) ischaracterised by multi-system organ inflammation, endothelial wall damage and vasculopathy (1). There are many markers of endothelial dysfunction and/or atherosclerotic risk, such as asymmetric dimethylarginine (ADMA), arterial stiffness parameters, carotid intima-media thickness (cIMT) and coronary flow reserve (CFR) assessed by means of trans-thoracic echocardiography (TTE). <h3>Objectives</h3> The aim of this pilot study was to use various endothelial and atherosclerosis markers to identify early CV involvement in a group of SSc patients. <h3>Methods</h3> The study involved 20 patients (two males, 18 females; mean age 52.96±12.51 years) with diffuse SSc but no signs or symptoms of CV disease (CVD), and 20 age- and gender-matched controls. All underwent a dipyridamole echocardiographic stress test which included a determination of CFR, and an evaluation of cIMT, arterial stiffness and plasma ADMA levels. <h3>Results</h3> All the arterial wall measurements of the diffuse SSc group were significantly different from those of controls and both right and left cIMT, pulse wave velocity (PWV), and stiffness index β were also all significantly elevated in SSc patients compared to healthy controls (Table 1). Moreover, in patients with diffuse SSc CFR was significantly lower (P=0.0033) and plasma ADMA levels higher (P&lt;0.0001) than in healthy controls (Table 1). <h3>Conclusions</h3> This study showed that those SSc patients without any clinical evidence of CVD had subclinical atherosclerosis, which was suggested by early impairment of coronary microcirculation and macrovascular involvement. <h3>Disclosure of Interest</h3> None Declared