tbuckley/cabot-search huggingface dataset:
Abstract 1553: Rho guanine nucleotide exchange factor (ARHGEF) 10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma
Authors: Joella Joseph, Nikolina Radulovich, Ming-Sound Tsao
Journal: Cancer Research (2014)

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of pancreatic malignancies, and is the fourth leading cause of cancer related deaths. Disease prognosis is quite poor, with less than 20% of patients eligible for curative surgical resection at time of diagnosis and overall survival rates of 2%. PDAC arises from the malignant transformation of ductal epithelial cells through progressive accumulation of loss of function mutations and deletions of tumor suppressor genes. Chromosome 8p has been shown to be a recurrent site of deletions in PDAC. Among the deleted genes is the Rho guanine nucleotide exchange factor 10 (ARHGEF10), a regulator of Rho signaling that is involved in mitotic spindle formation. Here, we evaluate ARHGEF10 for its potential role as a tumor suppressor in PDAC. Methods: ARHGEF10 expression was assessed in 19 PDAC cell lines and in 53 patient tumor xenograft samples at both mRNA and protein levels. Publically available datasets were also used to determine correlation between ARHGEF10 mRNA expression and DNA copy number. After identifying PDAC cell lines with low ARHGEF10 expression, ARGHEF10 was stably overexpressed in these cell lines by lentiviral transduction. The effects of ARHGEF10 expression were then evaluated by in vivo tumorigenicity in immunodeficient mice, and by in vitro cell proliferation and cell motility wound healing assays. Results: ARHGEF10 showed reduced expression in up to 70% of cell lines and patient tumor xenografts. Reduced ARHGEF10 expression correlated significantly with loss of copy number in PDAC cell lines. Stable overexpression of ARHGEF10 in PDAC cell lines significantly reduced tumor growth in immunodeficient mice. In addition, ARHGEF10 expression resulted in decreased cell motility in wound healing assays, but had minimal effect on cell proliferation. Experiments for in vitro assessment of invasion and changes in Rho activity are ongoing, and will be presented Conclusions: This study suggests that ARHGEF10 may function as a tumor suppressor gene in PDAC. Citation Format: Joella Joseph, Nikolina Radulovich, Ming-Sound Tsao. Rho guanine nucleotide exchange factor (ARHGEF) 10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1553. doi:10.1158/1538-7445.AM2014-1553
Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo-HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective, multicenter Polish Adult Leukemia Group study
Authors: Sebastian Grosicki, Jerzy Holowiecki, Kazimierz Kuliczkowski, Aleksander Skotnicki, Andrzej Hellmann, Slawomira Kyrcz‐Krzemien, Anna Dmoszynska, Kazimierz Sułek, Janusz Kloczko, Wieslaw W. Jedrzejczak, Krzysztof Warzocha, Barbara Zdziarska, Agnieszka Wierzbowska, Agnieszka Pluta, Mieczyslaw Komarnicki, Sebastian Giebel
Journal: American Journal of Hematology (2015)

The importance of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo-HSCT. These consisted of leukemia-free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999-2008. The Mantel-Byar approach was used to assess allo-HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo-HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41-60. The CIR demonstrated that allo-HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo-HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41-60. The allo-HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis.
Wide Variety of Point Mutations in the H Gene of Bombay and Para-Bombay Individuals That Inactivate H Enzyme
Authors: Mika Kaneko, Shoko Nishihara, Naoko Shinya, Takashi Kudo, Hiroko Iwasaki, Taiko Seno, Yasuto Okubo, Hisashi Narimatsu
Journal: Blood (1997)
New developments have transformed outlook for patients with schizophrenia
Authors: R. M Murray
Journal: BMJ (1995)

technique, and outcome of peripheral thrombolysis for the past two years.2This is a continual process to provide a system for the national audit of peripheral arterial thrombolysis, and so far over 450 events of thrombolysis have been recorded.In these, only 13% of infusions were given with a pulse spray technique, in a median time of six hours (range 1-78 hours).Pulse spray lysis is certainly faster than conventional low dose techniques, but it requires expensive catheters and infusion systems.Other methods, such as high dose bolus thrombolysis and six hourly dose infusions, have also been reported to reduce infusion times without expensive equipment.34Personal communications with the manu- facturers of pulse spray infusion catheters also suggest that relatively few hospitals in Britain use the pulse spray technique.Little information is available on many of the techniques for peripheral thrombolysis, and low dose infusions remain the gold standard for many hospitals in Britain.
Characterization of potentially virulent non-O1/non-O139 Vibrio cholerae strains isolated from human patients
Authors: F.A.M.O. Cariri, A.P.R. Costa, C.C. Melo, G.N.D. Theophilo, E. Hofer, O.P. de Melo Neto, N.C. Leal
Journal: Clinical Microbiology and Infection (2009)
Abstract 6204: Potentially Modifiable Risk Factors in Adolescence and High Carotid Artery Intima-Media Thickness in Young Adulthood: Population Attributable Risks from Three Prospective Cohort Studies
Authors: Costan G Magnussen, Markus Juonala, Olli T Raitakari, Russell Thomson, Jorma S Viikari, Sathanur R Srinivasan, Gerald S Berenson, Terence Dwyer, Alison Venn
Journal: Circulation (2008)

Background: Exposure to cardiovascular disease risk factors in adolescence are associated with the development of atherosclerosis later in life. Nevertheless, the proportion of atherosclerosis that...
Apolipoprotein e4 allele and cognitive decline
Authors: G B Frisoni, A Bianchetti, G Franceschini, S Govoni, M Trabucchi
Journal: BMJ (1995)

confounding effect of these factors, it may intro- duce a new bias.If the matching factor is associated with the exposure of interest a crude case-control analysis may lead to a result that is confounded by the matching factor itself.2In such a case the confounding must be eliminated by stratified analysis or multivariate analysis.Another potential problem is overmatching, which results from cases and controls being matched on variables that are highly related to the exposure.For example, suppose one matches on the variable "carrying a cigarette lighter" in a study of smoking and lung cancer.Matched analyses depend on the existence of discordant pairs of cases and controls, but few will exist in this situation because the confounder is closely related to the exposure.Overmatching will not bias the results, but it will make the analysis highly inefficient, which abrogates the main virtue of matching.2In case-control studies investigators must use the technique of matching wisely since it is irrever- sible and its advantages may be limited by the problems we have highlighted.
Multiple Myeloma
Authors: Kenneth C. Anderson, Melissa Alsina, William Bensinger, J. Sybil Biermann, Asher Chanan-Khan, Adam D. Cohen, Steven Devine, Benjamin Djulbegovic, Cristina Gasparetto, Carol Ann Huff, Madan Jagasia, Bruno C. Medeiros, Ruby Meredith, Noopur Raje, Jeffrey Schriber, Seema Singhal, George Somlo, Keith Stockerl-Goldstein, Guido Tricot, Julie M. Vose, Donna Weber, Joachim Yahalom, Furhan Yunus
Journal: Journal of the National Comprehensive Cancer Network (2009)

Multiple myeloma (MM) is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure.The American Cancer Society estimates that 20,580 new cases of MM will occur in the United States in 2009, including 11,680 in men and 8900 in women, with an estimated 10,580 deaths. 1 The mean age of affected individuals is 62 years for men (75% > 70 years) and 61 years for women (79% > 70 years).The treatment of MM has dramatically improved over the past decade.The 5-year survival rate reported in the Surveillance Epidemiology and End Results database has increased from 25% in 1975 to 34% in 2003 because of the availability of newer and more effective treatment options. 2,
Abstract 11954: Whole Body Periodic Acceleration (pGz) Decreases Hypoxia Induced Apoptotic Signaling in the Brain of Newborn Piglets
Authors: Jose A Adams, Gregory Schears, Anna Pastuszko, David F Wilson, Paul Kurlansky, Vinay M Nadkarni, William J Greeley
Journal: Circulation (2011)

Hypoxic brain injury (HI) can be a devastating complication in neonates and infants, associated with apoptosis in vulnerable brain regions (e.g. cortex, hippocampus, striatum) where effective neuro...
Acute Lymphoblastic Leukemia (ALL) With Low-Hypodiploid/Near-Triploid Karyotype Is a Specific Clinical Entity Characterized By a High TP53 Mutation Frequency
Authors: Verena Patterer, Melanie Zenger, Susanne Schnittger, Sandra Weissmann, Franziska Poetzinger, Alexander Kohlmann, Frauke Bellos, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2013)
Behavioral Mechanisms, Elevated Depressive Symptoms, and the Risk for Myocardial Infarction or Death in Individuals With Coronary Heart Disease
Authors: Siqin Ye, Paul Muntner, Daichi Shimbo, Suzanne E. Judd, Joshua Richman, Karina W. Davidson, Monika M. Safford
Journal: Journal of the American College of Cardiology (2013)
A 6-Year-Old Boy With Fever, Emesis, Rash, and an Acute Abdomen
Authors: Jennifer L. Rammel, K. Leigh Bragg, Jose Zayas
Journal: JAMA Pediatrics (2015)

Apreviously healthy 6-year-old boy presentedwith 6 days of fever (maximum temperatureof40°C), intermittentnonbiliousemesis, and4daysof crampy,diffuseabdominalpain. Physical examination findingsweresignificant for ill appearance,bilateralnonexudativeconjunctivitis, shotty bilateral anterior cervical lymphadenopathy, diffuse abdominal tenderness (greatest in the right upper quadrant), and associated rebound and guarding. There was also a blanching, erythematous, macular rash on his cheeks (Figure, A) and an intermittent, erythematous, reticular rash on his chest, abdomen,arms,and legs (Figure,B) that sparedhispalmsandsolesand flaredwith fever.Theremainderofhisexaminationfindingswereunremarkable.Laboratorystudieswere significant for an elevated aspartate transaminase level of 264 U/L (reference range, 12-47 U/L; toconvert tomicrokatalsper liter,multiplyby0.0167)andanalanine transaminase level of251U/L (reference range, 17-63U/L; toconvert tomicrokatalsper liter,multiplyby0.0167). Acompletebloodcell count revealed leukopeniawithawhitebloodcell countof28300/μL (to convert to ×109/L, multiply by 0.001) (neutrophils, 64%; lymphocytes, 18%; monocytes, 4%; eosinophils, 2%; basophils, 1%; and bands, 11%), a low-normal hemoglobin level of 11.4g/dL (toconvert togramsper liter,multiplyby 10), andthrombocytopeniawithaplatelet countof610× 103/μL (to convert to×109/L,multiplyby 1). Computed tomographyof the abdomen revealed a dilated appendix (7 mm) with mucosal hyperemia and an internal appendicolith; acute appendicitis could not be excluded radiographically, so the patient was admitted for further workup because of a concern for acute abdomen. The patient lives in the southeasternUnited States and had no reported history of unusual exposures or insect or tick bites. Quiz at jamapediatrics.com Macular rash on bilateral cheeks A Reticular rash on left arm B
Abstract 15697: Cocaine-Induced Ischemia in the Human Coronary Microcirculation: Evidence from Myocardial Contrast Echocardiography
Authors: Swaminatha V Gurudevan, Michael D Nelson, Xiu Tang, Jimmy Johannes, Joshua Lewis, J T Belcik, Jonathan R Lindner, Ronald G Victor
Journal: Circulation (2012)

Background:  Cocaine commonly causes acute coronary syndrome but the exact mechanism is unknown and thus treatment remains empirical. We used myocardial contrast echocardiography (MCE) to test the hypothesis that cocaine, an indirect sympathomimetic stimulating both vascular α- and cardiac β- adrenergic receptors, causes microvascular ischemia in the human heart by decreasing myocardial capillary perfusion while increasing myocardial oxygen demands.   Methods:  Six healthy cocaine-naive male subjects (median age 38Y) were studied at baseline, 45 min after non-intoxicating low-dose intranasal cocaine (2 mg/kg), and during dobutamine (5 mg/kg i.v.), a β-agonist used as an internal control. Measurements included heart rate (HR), mean arterial pressure (MAP), and left ventricular (LV) work (end-systolic elastance x HR) by 2D echocardiography. MCE perfusion imaging was performed with a continuous infusion of microbubbles and post-destructive data were fit to the equation: y = A(1-e-βt) to quantify functional capillary blood volume (A), flux (flow) rate (β) and perfusion (Aβ). Myocardial oxygen consumption (MVO2) was estimated as: (7.2 x 10-4 x (HR x systolic BP) + 1.42). Microvascular conductance was calculated as perfusion divided by MAP.   Results:  Despite an increase (p   Conclusions:  In humans, cocaine-induced sympathoexcitation acts at the level of the coronary microvessels to cause a mismatch between myocardial oxygen demand and perfusion. Microvascular ischemia from inappropriately reduced functional capillary density constitutes a specific therapeutic target which could improve treatment of cocaine-induced acute coronary syndrome.
Stereoscopic viewing of the retina needed to identify maculopathy
Authors: R H B Grey, J C D. Hart
Journal: BMJ (1996)

EDITOR,—S P Harding and colleagues' detailed quantitative evidence showing the capabilities of direct ophthalmology and retinal photography is an important step in the establishment of worthwhile screening.1 Their emphasis on the photographic improvements obtained with dilatation of the pupil and use of 35 mm film in place of …
How To Do It: Work with an interpreter
Authors: M. Phelan, S. Parkman
Journal: BMJ (1995)

The Audit Commission recently highlighted the need for health services to plan language services to help the problems of poor communication facing non-English speaking patients. Doctors and other health workers need to know how to work effectively when interviewing patients with an interpreter. This article describes the different options for helping non-English speaking patients; explains how interviews should be conducted with a trained interpreter, including those using sign language; and outlines the extent of interpreting services currently available in the United Kingdom, complete with a list of addresses of organisations offering interpreting services.
Abstract 4137: Latent class model characterization of neighborhood SES
Authors: Aimee Palumbo, Yvonne Michael, Terry Hyslop
Journal: Cancer Research (2014)

Abstract Background: Breast cancer is the most common cancer in women and a significant source of mortality. Neighborhood-level socioeconomic status (NSES) has been shown to play a key role in health; poorer health outcomes are observed in deprived neighborhoods even after controlling for individual level SES. Commonly used NSES indexes are difficult to interpret. The relative impact of different factors within the index cannot be evaluated. Latent class models, which use latent variables to create distinct classes, allow for characterization of NSES and estimation of the effects of specific neighborhood characteristics on cancer outcomes. Methods: We used data from women diagnosed with breast cancer from a teaching hospital in Philadelphia, PA. Census information at the Zip Code Tabulation Area (ZCTA) level was used to obtain NSES variables. Latent class analysis and comparisons of model fit statistics were used to determine the optimal number of classes. Results: Complete ZCTA-level data was available for 1,664 breast cancer patients. In this population, NSES was best represented by two separate latent variables, each with 2-classes (LC2). When the class variables were compared to a continuous NSES index (NSI), the correlation was 0.85. However, LC2 demonstrated stronger association with race, stage, disease subtype, tumor size, and histologic grade. Conclusions: We classified neighborhoods based on correlated socioeconomic census-level variables. Latent variables identify specific characteristics associated with living in a neighborhood with low versus high advantage and disadvantage and thus may improve our understanding of critical breast cancer prognostic factors and the targeting of cancer control efforts. Further research will provide overall structural latent models that incorporate information on tumor biology, prognostic variables and survival outcomes to aid in the identification of vulnerable populations. Table 1. Neighborhood latent class model (LC2) and SES Index (NSI) Table 1.Neighborhood latent class model (LC2) and SES Index (NSI)LC2 *ModelNSI Model *Prognostic Factor Stage24.5511.61 Race366.44331.01 Subtype18.4315.48 Size22.532.91* Chi-square statistic for association of Prognostic Factor with LC2 class or with NSI quartile. Higher number indicates higher strength of association. Citation Format: Aimee Palumbo, Yvonne Michael, Terry Hyslop. Latent class model characterization of neighborhood SES. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4137. doi:10.1158/1538-7445.AM2014-4137
LSC 2013 abstract - An in vivo approach to determine the dynamic Sox2 interactome of the developing lung
Authors: Kim Schilders, Joshua Kapere Ochieng, Marjon Buscop-van Kempen, Anne Boerema-de Munck, Frank Grosveld, Dick Tibboel, Robbert Rottier
Journal: European Respiratory Journal (2013)

Sox2 is a Sry-box containing family member of related transcription factors sharing homology in their DNA binding domain. Sox2 is important during different stages of development, and previously we showed that Sox2 plays an important role in branching morphogenesis and epithelial cell differentiation in lung development. The transcriptional activity of Sox2 depends on its interaction with other proteins, leading to 9complex-specific9 DNA binding and transcriptional regulation.  To analyze Sox2 complexes, we created stable tagged-Sox2 A549 cell-lines in order to optimize and standardize procedures. Next, we developed a mouse model containing a biotinylatable-tag targeted to the endogenous Sox2 locus (bioSox2) to identify associating partners of Sox2 at different phases of lung development  in vivo  (the Sox2 interactome), and to identify  in vivo  DNA targets of Sox2 in the lung.  We analyzed if the biotinylatable Sox2 protein was functional and found that the bioSox2 was still able to bind to oligonucleotides containing the consensus Sox2 DNA binding site in vitro. In addition, homozygous bioSox2 mice with or without the biotin ligated to the tag are viable and fertile, indicating that the gene is normally expressed and the protein is functional in all tissues. This suggests that the normal partners of Sox2 are able to associate with bioSox2, since the absence of correct complex formation will lead to lethal phenotypes.  Our preliminary data show that it is possible to isolate bioSox2 complexes with high affinity and specificity using streptavidin beads. Currently, we are analyzing the initial data from our co-immunoprecipitations.
Impact of hematopoietic cell transplantation (HCT) for hematologic malignancies on self-reported fatigue and vigor
Authors: M. Gonzales, F. L. Wong, S. Patel, M. Grant, A. Bosworth, S. Forman, S. Bhatia, M. Grant
Journal: Journal of Clinical Oncology (2008)

9620 Background: HCT is used increasingly with curative intent for hematologic malignancies, creating a need to examine factors which impact survivors’ quality of life (QOL). Energy impairment is a debilitating outcome, yet few studies have examined long-term trends in fatigue and vigor after HCT. Objective: To determine the trajectories of fatigue and vigor in HCT recipients; to assess the contribution of demographic and medical factors on fatigue and vigor; and to determine the impact of energy impairment on QOL. Methods: Using a longitudinal study design, fatigue and vigor levels were evaluated in 211 adult City of Hope HCT recipients using the Profile of Moods States at pre-HCT, six months, and 1 year post-HCT. Four QOL domains (physical, psychological, social, and spiritual) were assessed at the same time points using the City of Hope QOL Instrument. Generalized Estimating Equation was used to estimate longitudinal trends adjusting for potential confounders. The cohort included 60% males, 36% undergoing allogeneic HCT, with a mean age of 51y at HCT. Seventy-nine patients completed 1y follow-up. Results: Mean fatigue and vigor scores were within the normal range before and after HCT. Fatigue did not change over time, but vigor increased over the 1y after HCT (p<0.05). Lower vigor after HCT was reported by older (>45y) patients (p=0.03), college graduates (p=0.05), those with chronic graft versus host disease (cGVHD) (p=0.04), and those with higher levels of depression (p<0.0001). Fatigue after HCT was greater in males (p<0.001), and those with less than college degrees (p<0.05). Additionally, higher fatigue occurred in those with greater depression (p<0.0001), higher pain (p<0.003), and cGVHD (p<0.003). Low vigor and high fatigue significantly reduced all domains of QOL (p<0.003), demonstrating the impact of treatment-related energy impairments on QOL. Conclusions: Although there were subgroups with lowered energy, overall, patients were within the normal ranges of fatigue and vigor. Vigor improved over time after HCT; however, in those with lower levels after HCT, QOL was significantly diminished. Patients with depression and cGVHD represent vulnerable subgroups that may benefit from targeted intervention. No significant financial relationships to disclose.
Isolation of Tumor-Specific Cytotoxic CD4+ and CD4+CD8dim+ T-Cell Clones Infiltrating a Cutaneous T-Cell Lymphoma
Authors: Martine Bagot, Hamid Echchakir, Fathia Mami-Chouaib, Marie-Hélène Delfau-Larue, Dominique Charue, Alain Bernheim, Salem Chouaib, Laurence Boumsell, Armand Bensussan
Journal: Blood (1998)
Dutch investigate if carcinogenic effects of diethylstilbestrol persist
Authors: Tony Sheldon
Journal: BMJ (2001)

The Dutch Cancer Institute has launched the largest ever study into the long term effects of prescribing the hormone diethylstilbestrol (DES) to pregnant women.

During the next four years the institute is to investigate 17 000 postmenopausal women whose mothers were prescribed the synthetic oestrogen in the belief that it prevented miscarriage. The drug was prescribed from 1947 until 1975, and an estimated 110 000 girls were born to mothers who took it. …