tbuckley/cabot-search huggingface dataset:
P1-05-06: Hypermethilation 14-3-3- Sigma Promoter as a Biomarker to Screening for Metastasis and Potencial Prognostic Factor in Breast Cancer Patients.
Authors: J Martinez-Galan, B Torres-Torres, A González-Vicente, J Ruiz-Vozmediano, JR Delgado-Pérez
Journal: Cancer Research (2011)

Abstract Background: 14-3-3sigma is an epithelial marker whose expression is induced by DNA damage through a p53-dependent pathway. 14-3-3sigma functions sequesters cyclin B1-CDC2 complexes outside the nucleus and thereby contributes to a G2 arrest. Epigenetic silencing by CpG methylation, p53 inactivation, and proteasome-dependent proteolysis leads to loss of 14-3-3sigma and is often observed in precancerous lesions and likely to be causally linked to the onset of cancer Objetive: To correlation methylation levels of promoter 14-3-3 sigma with association prognostic factors in breast cancer and their correlation with phenotype luminal. Material and Methods: This is a prospective study we quantified methylation levels of promoter 14-3-3 sigma gene in 107 women with breast cancer and 108 control subjects by Real Time QMS-PCR SYBR green (methylation-specific PCR) and analyzed association with prognostics factor in breast cancer. Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement N0; 63%,N1;30%,N2;7%), tumor size (T1;58%,T2;35%,T3;4%,T4;4%) and grade G1; 20%,G2;37%,G3;30%). Significant differences between breast cancer patients (pts) and healthy controls in relative serum levels of methylated gene promoters 14-3-3s (p=0.0047) were detected. Presence of methylated 14-3-3-s in serum of breast cancer patients was associated with T3-4 stage (OMS) (p&amp;lt;0.05) and nodal positive status (p&amp;lt; 0.05). With a median follow up 6 years we saw more probability of developing distance metastasis in patients with methylation 14-3-3 sigma (p&amp;gt;0.05). Conclusions: Hypermethylation of the 14-3-3 sigma promoter is an early and frequent event in breast neoplastic transformation, leading to the suggestion that silencing of 14-3-3 sigma may be an important event in tumor progression and particularly in breast carcinogenesis. This study identifies the presence of variations in global levels of methylation promoters genes in patients breast cancer with different phenotype classes and shows that these differences have clinical significance. Perhaps in the detection of CpG methylation of 14-3-3sigma may be used for diagnostic and prognostic purposes. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-05-06.
Case 31-2003
Authors: Lawrence D. Kaplan, Nadeem A. Afridi, Godtfred Holmvang, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 44-year-old man was seen in the clinic because of a right atrial mass.Six years earlier, the patient had been found to have Pneumocystis carinii pneumonia and human immunodeficiency virus (HIV) infection. He had returned to a satisfactory state of health with the use of highly active antiretroviral therapy. He did not have severe disabling symptoms from either the HIV infection or its management.Ten months before being seen in the clinic, he had an episode of substernal pain that lasted nine hours. An exercise stress test performed at another hospital did not provoke chest pain . . .
Substantial Increase in Myocardial FDG Uptake on Interim PET/CT May Be an Early Sign of Adriamycin-Induced Cardiotoxicity
Authors: Arun Kumar Reddy Gorla, Ashwani Sood, Gaurav Prakash, Madan Parmar, Bhagwant Rai Mittal
Journal: Clinical Nuclear Medicine (2016)

Cumulative cardiotoxicity is a well-established adverse effect of Adriamycin therapy. Although dose dependent, cardiotoxicity has been recently reported to occur even at lower doses than usually proposed. Conventional imaging detection and/or clinical manifestation of the deterioration in cardiac function occur late in the process; thus, it is desirable to have noninvasive markers to detect toxicity at an early stage. Several biochemical markers including troponin and atrial natriuretic peptide were explored for this purpose. The present case depicts that a significant increase in myocardial FDG uptake on posttherapy PET/CT can be a potential imaging biomarker of Adriamycin-induced cardiotoxicity.
Abstract 5237: Development of organ-selective neuroblastoma cell lines to identify genes mediating bone marrow and liver colonization
Authors: Zillan Neiron, Kacper Jankowski, Jayne Murray, Sophia Champion, Murray D. Norris, Michelle Haber, Jamie I. Fletcher
Journal: Cancer Research (2011)

Abstract Neuroblastoma is a pediatric tumor with a high propensity for metastasis to bone marrow, cortical bone and liver, and almost 50% of patients have metastatic disease at diagnosis. This study aims to identify genes contributing to neuroblastoma colonization of the bone marrow and liver through a combination of in vivo cell selection techniques and gene expression analyses. Ultimately, it aims to identify potential therapeutic targets for this disease. When the human neuroblastoma cell line SK-N-BE(2) is xenografted into immunodeficient mice, metastases arise in the adrenal medulla, liver and bone marrow. In contrast, an established subclone forms metastases limited to the bone marrow, suggesting that the original line contains populations with different abilities to colonise each site. We xenografted luciferase positive SK-N-BE(2) cells into immunodeficient mice and isolated pure tumour cell populations from the bone marrow and liver. Increased selectivity for the organ of origin was confirmed for some of these populations using bioluminescent imaging following engraftment into secondary recipients. We conclude that neuroblastoma cell populations with selectivity for particular organs can be generated using in vivo selection methods. Whole genome expression analyses will now be used to identify candidate genes underlying this selectivity. These genes will subsequently be validated in xenograft models. 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 5237. doi:10.1158/1538-7445.AM2011-5237
PMO-063 Outcomes of patients on home parenteral nutrition from a regional intestinal failure unit: Abstract PMO-063 Table 1
Authors: J A Saunders, M Naghibi, T R Smith, A T King, Z B Leach, M A Stroud
Journal: Gut (2012)

<h3>Introduction</h3> HIFNET proposals to create regionalised services for intestinal failure (IF) in England led us in 2007 to start active development of our small pre-existing regional IF activities and consequent expansion of our IF network. We report our outcomes compared to other published data. <h3>Methods</h3> Data were retrospectively collected from electronic and paper records for adult patients who received HPN between January 2001 and October 2011. <h3>Results</h3> Data were available for 79/81 patients (45 female) who received HPN for a period of 160 patient-years. 45 (57%) patients were regional referrals, 21 (27%) patients had type 2 intestinal failure and 58 (73%) type 3. The total number of patient-days in 2011 was 11 787 (type 2 2748, type 3 9039) compared to 4524 in 2007 (type 2 60, type 3 4464), despite only 10 months of 2011 data available at time of data collection. The period prevalence of patients on HPN in 2011 was 42 compared to 11 in 2007, a 381% increase. The median duration patients were treated was 230 days in 21 type 2 patients and 712 days in 47 type 3 (excluding palliative HPN), with on-going treatment in 37 patients. The rate of catheter related sepsis was 1.16 per 1000 patient days, comparable to 0.86 per 1000 patient days reported by one national centre.<sup>1</sup> The line occlusion rate was 0.27 per 1000 patient days and no episodes of bacterial endocarditis, similar to data from another regional unit, 0.68 per 1000 days and 0.05 per 1000 days respectively.<sup>2</sup> There were eight deaths (excluding palliative HPN), of which three were liver complications of type 3 IF in patients who were either ineligible or declined transplantation. <h3>Conclusion</h3> These data demonstrate a significant increase in HPN activity, particularly the last 5 years and the need for regional IF centres to cope with previous limited national capacity. Despite this increase in demand, quality outcome measures were comparable with those from other regional and nationally funded units. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Green CJ</b>, Mountford V, Hamilton H, <i>et al.</i> A 15-year audit of home parenteral nutrition provision at the John Radcliffe Hospital, Oxford. <i>QJM</i> 2008;<b>101</b>:365–9. 2. <b>Lloyd DA</b>, Vega R, Bassett P, <i>et al.</i> Survival and dependence on home parenteral nutrition: experience over a 25-year period in a UK referral centre. <i>Aliment Pharmacol Ther</i> 2006;<b>24</b>:1231–40.
SP0184 Clinical Implications of Imaging Advances
Authors: E. Naredo
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Modern imaging modalities have become increasingly implemented in rheumatology practice thanks to the growing evidence body regarding their role in optimizing diagnosis and management of rheumatologic patients. There are new publications that support the clinical added value of imaging techniques in the diagnosis, therapy monitoring and prognostication of inflammatory arthritis in both adults and children. In addition, some new published papers deals with promising applications of imaging techniques in osteoarthritis, microcrystalline arthritis, connective tissue diseases and vasculitidis. This lecture offers an update of current and emerging applications and research of imaging techniques in Rheumatology. <h3>Disclosure of Interest</h3> None Declared
Multidrug Resistance in<i>Aspergillus fumigatus</i>
Authors: Adilia Warris, Corry M. Weemaes, Paul E. Verweij
Journal: New England Journal of Medicine (2002)

To the Editor: Antifungal azoles with activity against aspergillus include itraconazole and three new drugs: voriconazole, posaconazole, and ravuconazole. Voriconazole was recently approved for the...
Abstract 4429: An investigation on p21-activated protein kinase 1 inhibitor, IPA-3, in hepatocellular carcinoma
Authors: Leo LY Wong, Ian Lam, Tracy Y N Wong, Benny WL Lai, Yuan Zhou, Red Hung, Wilson YP Ching
Journal: Cancer Research (2012)

Abstract Background: Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to metastasis and tumor recurrence. However, apart from Sorafenib, there is no proven effective systemic chemotherapy for HCC yet. Our previous study showed that overexpression of p21-activated protein kinase 1 (PAK1) is commonly found in HCC, which is coupled with a more aggressive tumor behavior. In this study, we examined the effect of an allosteric inhibitor of PAK1, IPA-3, on hepatocarcinogenesis. Methods: Human HCC line H2M was treated with various dosages of IPA-3 or vehicle control in order to measure the phospho-PAK1 level. The cells were also subjected to different functional assays, including proliferation assay, transwell assay and colony formation assay, to examine the anti-cancer effect of IPA-3. Tumor xenografts in nude mice were used to examine the in vivo activity of IPA-3. Results: Pretreatment with IPA-3 dose-dependently suppressed fetal bovine serum (FBS)-, and tumor necrosis factor (TNF)-α-induced PAK1 activity. The inhibitory effect was causally accompanied with suppression on cell migration, and enhancement of cell spreading. Furthermore, IPA-3 treatment on HCC cell line demonstrated a suppression of cell growth. The concomitant increase in apoptosis and delay in DNA synthesis had suggested a mechanism explaining the inhibition of HCC proliferation. In vivo, intraperitoneal administration of IPA-3 to subcutaneous xenograft mouse model significantly reduced the tumor growth rate. Conclusion: Taken together, these data showed that IPA-3 restrains cancer cell tumorigenicity and metastasis, thus, suggesting the potential use of IPA-3 in cancer therapy. 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 4429. doi:1538-7445.AM2012-4429
AB0770 Rheuma-card: involvement of the patient through a secure systems access into the treat to target strategy in rheumatology.
Authors: G. Ferraccioli, F. Salaffi, G. Lapadula
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Computer technology and Internet access are becoming increasingly available. A recent report published by the National Institute of Statistics showed at the end-2011 that 58.7% of Italian families (35.800.000) had a personal computer (slightly higher than the 57.6% in 2010); from 2006 to 2011 a significantly increased proportion of households had a fast connection to access the Internet from home (14.4 percent in 2006 to 45.8 percent in 2011). <h3>Objectives</h3> The RHEUMA-CARD (Complete Access to Rheumatologic Data) is a project, specifically designed to address the problem of enabling secure access to health information through Internet, not just for healthcare providers and medical personnel, but also for patients to view their own medical records and judge on the outcomes reached with their rheumatologists. <h3>Methods</h3> The project is using familiar Web technologies to support the search and retrieval of clinical information, of the GISEA registry. The GISEA registry is an independent database, established by the Italian Group for the Study of Early Arthritis (GISEA) in 2008, designed for collecting long-term follow-up data concerning patients with rheumatic diseases treated with biological agents in order to investigate the realworld characteristics in terms of disease activity, comorbidities and survival on treatment (1). <h3>Results</h3> The GISEA registry contains up to now more than 7000 patients (Table 1) <h3>Conclusions</h3> The proposed method for Internet-based exchange of patient data is particularly useful for cooperative healthcare and the creation of lifetime healthcare records. RHEUMA-CARD is designed to give patients as well as providers access to personal health records via Internet in order to reach the major outcomes. <h3>References</h3> Lapadula G et al. Reumatismo. 2011;63:155-64 <h3>Disclosure of Interest</h3> None Declared
PREVALENCE OF ERRORS IN FRACTIONAL FLOW RESERVE MEASUREMENT IN A HIGH VOLUME TERTIARY CARE CENTER
Authors: Arsalan Riaz, Mirza Nubair Ahmad, Fatima Husain, Syed Shahab Kazmi, Imran Husain, Haroon Yousaf, Khawaja Afzal Ammar, Anjan Gupta
Journal: Journal of the American College of Cardiology (2015)
Pediatric Neurology: Principles and Practice
Authors: Gerald F. Tremblay
Journal: JAMA (1989)

This book and its predecessor,The Practice of Pediatric Neurology, is to child neurologists what Harrison'sPrinciples of Internal Medicineis to internists. It is the most comprehensive textbook of the specialty. There are 79 chapters, 18 of which were written by Kenneth Swaiman, who also edited the contributions of 43 different authors. Despite the many contributors, the attractive format and clear style are preserved throughout.  The five chapters (67 pages) of part one, all written by Dr Swaiman, are devoted to the neurological examination at different ages. Part two (two chapters) reviews electroencephalography, evoked potentials, and the spinal fluid examination. Part three consists of 15 chapters on manifestations of neurological disease, and the last and longest section of the book, part four, comprises 50 chapters (more than 900 pages) on specific diseases.  Because of the many contributors and inevitable time lag between solicitation of manuscripts and their publication, there
A Complementary Affair
Authors: Owen N. Mogabgab, Nora Y. Osman, Kevin Wei, Ibrahim Batal, Joseph Loscalzo
Journal: New England Journal of Medicine (2016)

A 57-year-old man with a history of Sjögren's syndrome presented with several weeks of gradually worsening fatigue and exertional dyspnea. He reported no cough, fevers, chills, chest pain, palpitations, orthopnea, or paroxysmal nocturnal dyspnea.
Abstract LB-332: MDM4 transcription is discordantly regulated by common variants of p53
Authors: Russell Bainer, John Marioni, Luis Barriero, Ran Blekhman, Kenan Onel, Yoav Gilad
Journal: Cancer Research (2010)

Abstract The transcription factor p53 is a central mediator of the DNA damage response programs controlling cell cycle arrest and apoptosis that are critical to the prevention of oncogenesis. Although p53 has been subject to intense study, the functional consequences of the common proline to arginine coding polymorphism at codon 72 have yet to be fully elucidated. We hypothesized that the previously reported difference in apoptotic potential between cells expressing the two common p53 alleles may be due in part to differences in each variant's ability to transcriptionally regulate downstream target genes. To test this, we used a combination of expression profiling and ChIP-on-chip techniques to identify differences in the transcriptional networks regulated by the alternate alleles of p53 in isogenic cell lines. Our results indicate that although the majority of p53 transcriptional targets are equivalently regulated by both allelic variants, a small number of genes are specifically regulated by the respective versions of p53. Surprisingly, among the genes differentially induced by alternate p53 variants is MDM4 (HDMX), a well-characterized regulator of p53 activity. We subsequently used luciferase expression assays to identify a functional site containing a putative p53 binding element within the MDM4 promoter that discordantly interacts with the two p53 variants. These data provide the first evidence that MDM4 transcription is directly mediated by p53, and suggest a mechanism that could contribute to previously-reported differences in apoptotic potential between the common p53 alleles. 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 LB-332.
Urinary Dialkyl Phosphate Concentrations and Lung Function Parameters in Adolescents and Adults: Results from the Canadian Health Measures Survey
Authors: Ming Ye, Jeremy Beach, Jonathan W. Martin, Ambikaipakan Senthilselvan
Journal: Environmental Health Perspectives (2015)

Background:Epidemiological studies have reported associations between lung function parameters and organophosphate (OP) pesticide exposures in agricultural occupations, but to our knowledge associations have not been evaluated in general populations.Objectives:We examined associations between OP metabolite dialkyl phosphates (DAPs) and lung function using data from the Canadian Health Measures Survey (CHMS) Cycle 1.Methods:Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC (FEF25%–75%) were measured for 4,446 CHMS participants. Urinary concentrations of six DAP metabolites (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP), smoking status, and other predictors of lung function were also measured in the CHMS-Cycle 1. Multiple linear regression analyses were used to examine the relationship between total DAP concentrations (ΣDAPs) and lung function in adolescents (12–19 years) and adults (20–79 years).Results:In adults, estimates from multiple regression analyses suggested that a 1-unit increase on natural logarithmic scale (171% increase on the original scale) in the creatinine-corrected urinary concentration (nanomoles per gram creatinine) of ΣDAP was associated with a 32.6-mL (95% CI: –57.2, –8.1) reduction in FVC, 32.6-mL (95% CI: –59.0, –6.3) reduction in FEV1, 0.2% (95% CI: –0.6, 0.2) reduction in FEV1/FVC ratio, and 53.1-mL/sec (95% CI: –113.9, 7.7) reduction in FEF25%–75%. In adolescents, associations between ΣDAP and FEV1 were closer to the null and positive for FVC, whereas associations with FEV1/FVC and FEF25%–75% were negative, as in adults. However, none of the associations were significant in adolescents.Conclusions:The negative association between ΣDAP and lung function in adult participants suggests a detrimental effect of OP pesticides on lung function in the adult general population. Further studies using prospective designs are warranted to confirm the findings reported in this study.Citation:Ye M, Beach J, Martin JW, Senthilselvan A. 2016. Urinary dialkyl phosphate concentrations and lung function parameters in adolescents and adults: results from the Canadian Health Measures Survey. Environ Health Perspect 124:491–497; http://dx.doi.org/10.1289/ehp.1509745
Paradoxical Effect of Vagus Nerve Stimulation on Heart Rate in Dogs
Authors: Matthew N. Levy, Paul J. Martin, Thelma Iano, Harrison Zieske
Journal: Circulation Research (1969)

In the anesthetized, open-chest dog, electrical stimulation of the cardiac ends of the transected cervical vagus nerves produced effects on heart rate and A-V transmission that were dependent upon the P-St interval, i.e., the-time from the beginning of the P wave to the beginning of the stimulus. When one vagal stimulus was delivered per cardiac cycle, the pacemaker response curve (curve of the P-P interval as a function of the P-St interval) was sinusoidal in configuration, with a maximum at a P-St interval of 135 msec and a minimum at 349 msec. The mean P-P interval was 568 msec, and the mean amplitude of the pacemaker response curve was 58 msec. In any given experiment, the range of P-P intervals encompassed by the pacemaker response curve defined a range of frequencies over which S-A nodal rhythm became synchronized with the activity in the vagus nerves. Over such a range, increases in the frequency of vagal stimulation evoked paradoxical increases in heart rate. On either side of this range of synchronization, vagal stimulation elicited pronounced rhythmic oscillations of P-P and P-R intervals. The frequency of such oscillations was equal to the difference between the vagal stimulation frequency and the mean heart rate. The oscillations in P-R interval were approximately 180° out of phase with the oscillations in P-P interval.