tbuckley/cabot-search huggingface dataset:
FRI0262 Effectiveness of Biological Therapy Using A Treat to Target Strategy in Patients with Rheumatoid Arthritis:
Authors: P. Santos-Moreno, G. Saavedra-Martinez, L. Villarreal, A. Palomino, V. Giraldo, D. Gomez, J. Bello-Gualtero
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The implications of disease activity in progression and use of composite disease activity measures in rheumatoid arthritis (RA), led to developing of defined therapeutic targets and tools to achieve them resulting in the Treat to Target (T2T) initiative. <h3>Objectives</h3> The aim of this study was to describe general change in Disease Activity Score 28 (DAS28) using A T2T strategy during a 24 month period in RA patients treated with biological DMARDs. <h3>Methods</h3> A descriptive cross-sectional study was performed. Patients from a rheumatologic center with diagnosis of RA (ACR 1987 and 2010 ACR/EULAR criteria) were assessed applying a T2T strategy. A standardized follow-up was designed using DAS28: every 3-5 weeks (DAS28 &gt;5.1), every 7-9 weeks (DAS28 ≥3.2 and ≤5.1), and every 11-13 weeks (DAS28 &lt;3.2). In case of DAS28 &gt;3.2 it was mandatory to introduce adjustments in treatment based on a predetermined clinical guideline. We calculated percentages and averages from this data and divided patients in four groups: remission (Rem), low disease activity (LDA), moderate disease activity (MDA) and severe disease activity (SDA). Global change in DAS28 was determined at beginning, 6, 12, and 24 months an assessed using Chi-square test. <h3>Results</h3> 340 patients were included in this study, 304 (89.4%) women and 36 (10.6%) men. All patients had established disease (more than 2 years of duration) and average age 58.6 y/o. Regarding entire cohort 143 patients (42.1%) were using anti-TNFs and 197 (58.9%) were using others molecules. The difference of medians for each variable showed improvement with statistical significance (p&lt;0.00). <h3>Conclusions</h3> This study shows general improvement of DAS28 in RA patients treated with biological DMARDs and applying a T2T strategy; it was found a globally increase in the percentage of patients in Remission group and decrease in MDA/SDA groups. Standard T2T follow-up in patients with RA should be done based on: correct use of disease activity scores and visits/treatment decisions based on, and was verified that achieving remission/LDA is a realistic goal in clinical practice. But, after 2 years there is a fourth of patients refractory to treatment with biologicals. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4815
New Regulations on Animal Research Add Costs, Variables
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article New Regulations on Animal Research Add Costs, Variables Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 20, 16 October 1991, Pages 1436–1438, https://doi.org/10.1093/jnci/83.20.1436 Published: 16 October 1991
RESTING HEART RATE AND LONG-TERM OUTCOMES IN AFRICAN AMERICANS: INSIGHTS FROM THE JACKSON HEART STUDY
Authors: Kishan S. Parikh, Melissa Greiner, Adam DeVore, Chad Blackshear, Takeki Suzuki, Lesley Curtis, Joseph Maher, Adrian Hernandez, Emily O'Brien, Robert Mentz
Journal: Journal of the American College of Cardiology (2016)
SAT0543 Reduced/Withdrawn Dose of Etanercept-Methotrexate Therapy of Early Rheumatoid Arthritis has a Favorable Impact on Patient-Reported Outcomes Compared with MTX Alone or Placebo: the Prize Study
Authors: P. Emery, P. Wiland, J. Dudler, R. M. Ionescu, B. Vlahos, J. Bukowski, R. Pedersen, T. Williams, S. Gaylord, S. Kotak
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Open-label etanercept (ETN) + methotrexate (MTX) therapy in early rheumatoid arthritis (RA) yielded high clinical remission and improvements in patient-reported outcomes (PROs) in PRIZE Phase 1 (moderate-severe RA ≤1yr; MTX and biologic naïve pts).<sup>1</sup> PRIZE (121-wks, 3-phases) evaluates ETN/MTX efficacy/efficacy maintenance and PROs with reduced/withdrawn therapy in Phase 2. <h3>Objectives</h3> To assess PROs in PRIZE Phase 2, a 39-wk, 3-arm, double-blind comparison of therapy reduction after a 52 wk induction of 50 mg QW ETN/MTX (Phase 1). <h3>Methods</h3> Pts achieving DAS28 remission (≤3.2 at wk 39, &lt;2.6 at wk 52) in Phase 1 (n=193) were randomized 1:1:1 for 25 mg ETN + MTX: MTX+PBO injection: PBO capsules + PBO injection. PROs assessed included the Health Assessment Questionnaire disability index (HAQ-DI); EuroQol-5 Dimensions utility score (EQ-5D); Short Form Health Survey P/MCS Physical/Mental Component Summary; Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue); Work Productivity and Activity Impairment Questionnaire (WPAI:RA) and Work Instability Scale for Rheumatoid Arthritis (RA-WIS). <h3>Results</h3> With dose reductions/withdrawals in Phase 2, the maintenance of effect in PROs was greater at LOCF in the ETN25 + MTX treatment group compared with the PBO group for: HAQ-DI, EQ-5D utility, EQ-5D VAS, SF-36 MCS/PCS, FACIT, and WPAI sub-scales. Additionally, at Phase 2 LOCF clinically meaningful improvements, relative to start of trial, in HAQ-DI (≥0.22); EQ-5D utility (≥0.05) and VAS &gt;82; SF-36 P/MCS (&gt;5) and statistically significantly greater proportions of pts with low and low/medium risk RA-WIS score (≤9 and ≤17) were observed in favor of ETN + MTX vs PBO; the relative benefits of MTX vs PBO were less. <h3>Conclusions</h3> ETN25 + MTX had a favorable impact on PROs compared to PBO, with greater maintenance of therapeutic effect from baseline to LOCF. <h3>References</h3> Emery P, <i>et al</i>. American College of Rheumatology/ARHP Annual Scientific Meeting - 2012;64(10):S1077; Abstract 2549. <h3>Acknowledgements</h3> The PRIZE study was funded by Pfizer Inc. <h3>Disclosure of Interest</h3> P. Emery Consultant for: Abbott, Bristol-Myers Squibb, Merck, Novartis, Pfizer Inc, Roche-Chugai, UCB Pharma Ltd, P. Wiland: None Declared, J. Dudler Consultant for: Swiss Pfizer Advisory Board, R. Ionescu: None Declared, B. Vlahos Employee of: Pfizer Inc, J. Bukowski Employee of: Pfizer Inc, R. Pedersen Employee of: Pfizer Inc, T. Williams Employee of: Pfizer Inc, S. Gaylord Employee of: Pfizer Inc, S. Kotak Employee of: Pfizer Inc
DECREASED RISK OF ISCHEMIC HEART DISEASE IN PATIENTS WITH SJGREN’S SYNDROME: AN ANALYSIS OF UNITED STATES NATIONAL DATABASE
Authors: Faraz Khan Luni, Osama Dasa, Abdur Rahman Khan, Haris Riaz, Douglas Federman, Yousuf Kanjwal, Sadik Khuder
Journal: Journal of the American College of Cardiology (2016)
Abstract SY15-01: Merkel cell polyomavirus: its role in pathogenesis and its potential as a molecular target.
Authors: Yuan Chang
Journal: Cancer Research (2013)

Abstract Merkel cell carcinoma (MCC) was first described as a pathologic entity in 1972, and is an uncommon but aggressive skin cancer with a high propensity for metastasis and recurrence. In 2008, a new human polyomavirus, Merkel cell polyomavirus (MCV) was discovered by digital transcriptome subtraction in an MCC lesion and is now one of eight new human polyomaviruses described in the past five years. MCV is part of the normal, healthy skin flora but causes cancer after viral genome mutations eliminate its replication capacity. Further, MCV is clonally integrated in 70-80% of MCC tumors suggesting a primary role for its involvement in MCV infected MCCs. The MCV genome is ~5400bp and has features including early, late, and non-coding regulatory regions conserved with other polyomaviruses. The MCV early region encodes for two potential viral oncoproteins: large T antigen (LT) and small T antigen (ST). Experiments show these proteins are expressed in MCC tumor cells from patient biopsies, and that MCV-positive MCC cell lines undergo growth arrest and/or cell death upon T antigen knockdown by short hairpin RNA (shRNA). These experiments provide direct experimental evidence that T antigen expression is necessary for the maintenance of MCV-positive MCC and that MCV is the infectious cause of MCV-positive MCC. While similar to known polyomaviruses, MCV oncogenes act in new ways, such as activation of the survivin oncoprotein and PP2A-independent targeting of cap-dependent translation. In five years, the diagnosis and treatment potential for an intractable and enigmatic cancer has dramatically changed through the discovery of a viral cause of MCC. Citation Format: Yuan Chang. Merkel cell polyomavirus: its role in pathogenesis and its potential as a molecular target. [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 SY15-01. doi:10.1158/1538-7445.AM2013-SY15-01
POOR EARLY HEMODYNAMIC AND BIOCHEMICAL RESPONSE IS ASSOCIATED WITH INCREASED IN-HOSPITAL MORTALITY IN PATIENTS RECEIVING PERCUTANEOUS VENTRICULAR ASSIST DEVICE SUPPORT FOR CARDIOGENIC SHOCK
Authors: David Berg, Devraj Sukul, Molly O’Brien, Benjamin Scirica, Ben Olenchock, Erin Bohula May, David Morrow
Journal: Journal of the American College of Cardiology (2015)
Abstract 3760: A novel PKC-iota inhibitor, ICA-1 abrogates cell proliferation in breast cancer
Authors: Shraddha Desai, Rekha Patel, Andrea N. McCray, Prajit Pillai, Mildred Acevedo-Duncan
Journal: Cancer Research (2012)

Abstract The objective of this research was to identify the efficacy of [4-(5-amino-4-carbamoylimidazol-1-yl)-2,3-dihydroxycyclopentyl] methyl dihydrogen phosphate (ICA-1) as a novel PKC-iota inhibitor in breast cell proliferation. PKC-α is highly overexpressed in human breast cancer and is localized depending on the trend of pathologic type of the tumor [Hum Pathol. (2008) 6:824-831]; however, little is understood about its role in regulating cell proliferation in breast cancer. Results showed that PKC-α was highly activated and overexpressed in MD-MB-468 breast cancer cells. PKC-α directly associated and phosphorylated Cdk7, a master cell cycle regulator at T170 in a cell cycle dependent manner, phosphorylating its downstream target, cdk2 at T160. PKC-α co-localized with Cdk7 in nuclear and cytoplasmic region of MD-MB-468 cells. PKC-α downregulation reduced Cdk7 phosphorylation following ICA-1 (10µM) as well as PKC-α silencing (by siRNA treatment). PKC-α knockdown inhibited overall proliferation in breast cancer cells suggesting that breast cancer cells may be proliferating through a PKC-α/Cdk7/cdk2 mediated pathway. Hence, our results emphasize the potential of ICA-1 as a novel PKC-α inhibitor and chemotherapeutic agent for breast 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 3760. doi:1538-7445.AM2012-3760
Abstract 1053: Modulation of Wnt/β-catenin signaling pathway by Cripto-1 in mouse embryonal carcinoma F9 cells
Authors: Tadahiro Nagaoka, Kazuhide Watanabe, Monica Gonzales, Nadia Castro, Maria-Cristina Rangel, Kelly Rollman, Jeffrey S. Rubin, David S. Salomon, Caterina Bianco
Journal: Cancer Research (2010)

Abstract Cripto-1 is a membrane bound protein that belongs to the epidermal growth factor (EGF)-CFC (Cripto/FRL-1/cryptic) protein family. Cripto-1 is a co-receptor for the transforming growth factor-β related protein Nodal and together with Nodal induces Smad-2/3 phosphorylation through the serine-threonine kinase receptor ALK-4. Furthermore, Cripto-1 can also bind to Glypican-1, Caveolin-1, GRP78, TGFβ1, Activin, Notch and Wnt11 proteins. In the present study, 3xFLAG-tagged human Cripto-1 and HA-tagged Wnt proteins (Wnt-1, 3a, 5a and 11) were co-expressed in 293T cells and co-immunoprecipitation was carried out using anti-FLAG or anti-HA antibodies. All four Wnt proteins were found to bind to Cripto-1. We also evaluated whether Cripto-1 could bind to the Wnt receptor, Frizzled-8 cysteine rich domain and the Wnt co-receptor, LRP5 in 293T cells. LRP5 was found to co-immunoprecipitate with Cripto-1 in transiently transfected 293T cells, while no binding of Cripto-1 to Frizzled-8 was detected. Finally, we investigated the biological significance of the interaction between various Wnts and Cripto-1 using mouse embryonal carcinoma F9 cells that express high levels of endogenous Cripto-1 protein and Cripto-1 gene null F9 (F9 Cr-1-/-) cells. Interestingly, we found that F9 cells contained more stabilized cytoplasmic β-catenin than F9 Cr-1-/- cells after the cells were treated with Wnt3a protein. Super TOP-FLASH reporter assays also revealed a significant increase in luciferase activity in F9 cells compared to F9 Cr-1-/- cells following Wnt3a treatment. In conclusion, our results demonstrate that Cripto-1 can enhance the canonical Wnt/β-catenin signaling pathway in mouse embryonal carcinoma cells. Therefore, modulation of the canonical Wnt/β-catenin pathway by Cripto-1 might perform an important role in embryonic stem cells and embryonal carcinoma cells that are expressing high levels of Cripto-1. 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 1053.
THE IMPACT OF ATRIAL FIBRILLATION ON CLINICAL OUTCOME AND MORTALITY ACCORDING TO SUBTYPE IN PATIENTS WITH AUTOIMMUNE RHEUMATIC DISEASES
Authors: Yongsoo Baek, Hancheol Lee, Tae-Hoon Kim, Jae-Sun Uhm, Kim Jong-Youn, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung
Journal: Journal of the American College of Cardiology (2016)
1038 ROLE OF GENE AND microRNAs EXPRESSION RELATED TO HEPATOCELLULAR CARCINOMA DEVELOPMENT IN A HCV-INDUCED MODEL IN VITRO. EFFECT OF METFORMIN
Authors: J.A. del Campo, M. García-Valdecasas Merino, Á. Rojas, P. Bensadoun, J. Pawlotsky, J. Muntané, F. Padillo, M. Romero-Gomez
Journal: Journal of Hepatology (2013)
In vitro and in vivo assessment of heart-homing porous silicon nanoparticles
Authors: Mónica P.A. Ferreira, Sanjeev Ranjan, Alexandra M.R. Correia, Ermei M. Mäkilä, Sini M. Kinnunen, Hongbo Zhang, Mohammad-Ali Shahbazi, Patrick V. Almeida, Jarno J. Salonen, Heikki J. Ruskoaho, Anu J. Airaksinen, Jouni T. Hirvonen, Hélder A. Santos
Journal: Biomaterials (2016)
Abstract 505: Multiscale mathematical model of skin reveals the critical role of stromal aging in melanoma initiation
Authors: Eunjung Kim, David Basanta, Vito Rebecca, Jane Messina, Rahel Mathew, Keiran S. Smalley, Alexander R. A. Anderson
Journal: Cancer Research (2011)

Abstract Melanoma initiation is known to involve specific genetic changes as well as the disruption of both cell-cell and cell-microenvironment interactions. However, the mechanisms by which dysregulated cell-cell interactions lead to melanoma development remain elusive. To better understand melanoma initiation and progression we have developed a hybrid multiscale mathematical model of normal skin (virtual skin). The model focuses on key cellular and microenvironmental variables that regulate normal homeostatic skin function, and is constructed to recapitulate how keratinocytes and fibroblasts regulate melanocyte proliferation, migration and death. Experimentally, we have shown that as fibroblasts age and become senescent their behavior changes significantly, leading to the expression of multiple growth factors, matrix proteins and proteases. We also showed, using 2D/3D culture, that interactions with senescent fibroblasts can aid melanoma initiation. Using our virtual skin model, we systematically investigated the effects of disrupting interactions between melanocytes, keratinocytes, fibroblasts and the microenvironment in driving melanoma initiation. The resulting virtual skin pathology readily recapitulates a spectrum of aberrant clinical pathology. Direct comparison between these pathologies allowed us to find the key perturbations leading to melanoma initiation and progression. To better understand the role of aging we also integrated senescent fibroblasts into our virtual skin model. Our primary finding is that melanoma initiation can be directly facilitated by fibroblast senescence. However, successful initiation requires the existence of preexisting mutations within the melanocyte population allowing them to exploit the stromal activation. These findings provide additional evidence demonstrating the importance of therapeutically targeting the stroma. We believe that any effective therapy will need to not only eradicate the melanoma population but also restore normal homeostatic stromal function. 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 505. doi:10.1158/1538-7445.AM2011-505
P40 A comparison of the value of oxygen shunt studies and cardiac bubble echo as screening tools for pulmonary arteriovenous malformations in patients with suspected hereditary haemorrhagic telangiectasia
Authors: J. Donaldson, K. Pointon, T. Mathew, A. Fogarty
Journal: Thorax (2010)

<h3></h3> Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder associated with recurrent spontaneous epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations (AVMs). Up to 30% of patients with HHT have pulmonary AVMs (PAVMs) which are associated with an increased risk of embolic stroke. Currently, with a sensitivity in excess of 98%, thoracic CT is the ‘gold standard’ for detecting PAVMs but involves a significant radiation exposure.1 Hence screening tools without a radiation burden such as oxygen shunt studies or cardiac bubble echo (CBE) are often considered as first line investigations for right-to-left shunts. With the recent introduction of CBEs to our hospital we collected data on patients who underwent both CBE and oxygen shunt studies. We looked retrospectively at 11 patients with suspected HHT (as defined by the Curacao criteria2) investigated over the last 5 years and aimed to determine the sensitivity and specificity of each screening test compared to thoracic CT (Abstract P40 Table 1). The oxygen shunt study had a sensitivity of 57% and specificity of 75%. CBE had 100% sensitivity (in five patients) but two studies were positive in the absence of detectable PAVMs on CT. Our data suggest that oxygen shunt studies are not sufficiently sensitive to be used as a screening tool for PAVMs. CBE is a useful initial screening test. A negative CBE combined with a negative chest x-ray has been shown to have a negative predictive value of 100% for PAVMs.3 This screening strategy is especially useful when the risk of CT irradiation is considered unacceptably high, for example in younger women. All patients with a positive CBE should undergo further imaging with thoracic CT to confirm the presence of PAVMs and to determine their size prior to consideration for embolisation therapy.
Ketoconazole in the Management of Precocious Puberty Not Responsive to LHRH-Analogue Therapy
Authors: F.John Holland, Leona Fishman, John D. Bailey, Atilla T.A. Fazekas
Journal: New England Journal of Medicine (1985)

Three boys 3.3 to 3.9 years old, who had precocious puberty that was unresponsive to an analogue of gonadotropin-releasing hormone, were treated with the antifungal agent ketoconazole for up to 12 months. Within 48 hours the serum testosterone concentration fell to normal in two boys and was significantly reduced in the third, paralleling major improvements in behavior. Reciprocal changes in serum levels of 17-hydroxyprogesterone suggested that C17-20 lyase was the principal site of drug action. Although there was evidence of a blunted cortisol reserve during the first week of treatment, the cortisol response to ACTH1-24 had returned to normal by one month of continuous treatment, and normal diurnal cortisol rhythm was preserved. No adverse clinical or biochemical side effects were noted during 9 to 12 months of continuing treatment. During that time, growth velocity was significantly reduced in all three boys, from a mean rate of 1.5 +/- 2.0 cm per year before treatment to 5.9 +/- 0.6 cm per year after ketoconazole therapy. There was a simultaneous retardation of the rate of skeletal maturation. The striking improvements in behavior were sustained for the duration of treatment. These preliminary data suggest that administration of ketoconazole may be a satisfactory treatment for precocious puberty in boys and possibly for other conditions characterized by androgen excess.
¿POR QUÉ DEBEMOS SEGUIR UTILIZANDO LA CÁPSULA ENDOSCÓPICA EN LA ENFERMEDAD INFLAMATORIA INTESTINAL?
Authors: S Bacchiddu, A Peláez, L Márquez, A Cañas, JM Dedeu, B Salcedo, J Llach, J Panés, M Andreu, B González Suárez
Journal: Endoscopy (2013)

Introducción: La cápsula endoscópica (CE) es una técnica útil en el diagnóstico y seguimiento de la enfermedad inflamatoria intestinal (EII). Material y Métodos: Determinar la utilidad de la CE en el diagnóstico y plan terapéutico de pacientes con sospecha de EII o con EII ya diagnosticada. Se incluyeron 242 individuos (262 CE), remitidos entre 2007 y 2012, para realizar CE por sospecha de EII (grupo A, 63 casos) o por aparición de nuevos síntomas/estudio de extensión en pacientes con EII establecida (grupo B, 188 casos, se registraron índice de Harvey-Bradshaw (H-B), PCR, VSG). Para valorar los resultados de la CE se utilizaron los índices de Lewis y CECDAI. Se analizaron las nuevas exploraciones y modificaciones de tratamiento tras la CE, la correlación entre índices endoscópicos y H-B, PCR/VSG. Resultados: Los hallazgos de la CE determinaron un nuevo diagnóstico en el 42.9% de casos (grupo A: 38.1%, 21 enfermedad de Crohn (EC), 3 otros diagnósticos; grupo B: 4.8%, 9 EC, con diagnóstico previo de colitis ulcerosa). En 30.3% de casos del grupo B se describió una nueva extensión de la EII (principalmente L1+L4 en 26 casos, L3+L4 en 10 casos). Los hallazgos de la CE indicaron la realización de nuevas exploraciones en un 26% de casos de ambos grupos (11 colonoscopias, 11 enteroRMN y 9 enteroscopias). En el 33.9% de casos del grupo A y en el 40.4% de casos del grupo B determinaron cambios en el tratamiento. Lewis y CECDAI mostraron un buen coeficiente de correlación (0.944, p < 0.001), pero no se observaron correlaciones estadísticamente significativas entre ellos y H-B, PCR y VSG. Conclusiones: La CE es una técnica útil en el diagnóstico de nuevos casos de EII y en la optimización del tratamiento en EII establecida. Los índices endoscópicos no tienen una buena correlación con los datos clínicos y analíticos.
The Role of Veterans Affairs Hospitals in the Health Care System
Authors: J W Hollingsworth, P K Bondy
Journal: New England Journal of Medicine (1990)

THE hospital system of the Department of Veterans Affairs (VA), formerly the Veterans Administration, represents the principal way the government provides medical care directly to civilians. It does so in close collaboration with the nation's medical schools, providing a major resource for educating physicians and other health care workers. This educational mission has grown in importance as medical school faculty members turn increasingly to the practice of medicine to earn the money they need to survive and as the Health Care Financing Administration loses enthusiasm for including the cost of medical education in its funding of health care. During the . . .