tbuckley/cabot-search huggingface dataset:
Magnetic Resonance Imaging Determination of Tumor Grade and Early Response to Temozolomide in a Genetically Engineered Mouse Model of Glioma
Authors: Patrick McConville, Dolores Hambardzumyan, Jonathan B. Moody, Wilbur R. Leopold, Alicia R. Kreger, Michael J. Woolliscroft, Alnawaz Rehemtulla, Brian D. Ross, Eric C. Holland
Journal: Clinical Cancer Research (2007)

The median survival for patients diagnosed with glioblastoma multiforme, the most common type of brain tumor, is less than 1 year. Animal glioma models that are more predictive of therapeutic response in human patients than traditional models and that are genetically and histologically accurate are an unmet need. The nestin tv-a (Ntv-a) genetically engineered mouse spontaneously develops glioma when infected with ALV-A expressing platelet-derived growth factor, resulting in autocrine platelet-derived growth factor signaling.In the Ntv-a genetically engineered mouse model, T2-weighted and T1-weighted, contrast-enhanced magnetic resonance images were correlated with histology, glioma grade (high or low), and survival. Magnetic resonance imaging (MRI) was therefore used to enroll mice with high-grade gliomas into a second study that tested efficacy of the current standard of care for glioma, temozolomide (100 mg/kg qdx5 i.p., n=13).The Ntv-a model generated a heterogeneous group of gliomas, some with high-grade growth rate and histologic characteristics and others with characteristics of lower-grade gliomas. We showed that MRI could be used to predict tumor grade and survival. Temozolomide treatment of high-grade tv-a gliomas provided a 14-day growth delay compared with vehicle controls. Diffusion MRI measurement of the apparent diffusion coefficient showed an early decrease in cellularity with temozolomide, similar to that observed in humans.The use of MRI in the Ntv-a model allows determination of glioma grade and survival prediction, distribution of mice with specific tumor types into preclinical trials, and efficacy determination both by tumor growth and early apparent diffusion coefficient response.
Infarct Remodeling After Intracoronary Progenitor Cell Treatment in Patients With Acute Myocardial Infarction (TOPCARE-AMI)
Authors: M.B. Britten, N.D. Abolmaali, B. Assmus, R. Lehmann, J. Honold, J. Schmitt, T.J. Vogl, H. Martin, V. Schächinger, S. Dimmeler, A.M. Zeiher
Journal: Circulation (2003)

Experimental and initial clinical studies suggest that transplantation of circulating blood- (CPC) or bone marrow-derived (BMC) progenitor cells may beneficially affect postinfarction remodeling processes after acute myocardial infarction (AMI). To relate functional characteristics of the infused cells to quantitative measures of outcome at 4-month follow-up, we performed serial contrast-enhanced MRI and assessed the migratory capacity of the transplanted progenitor cells immediately before intracoronary infusion.In 28 patients with reperfused AMI receiving either BMCs or CPCs into the infarct artery 4.7+/-1.7 days after AMI, serial contrast-enhanced MRI performed initially and after 4 months revealed a significant increase in global ejection fraction (from 44+/-10% to 49+/-10%; P=0.003), a decrease in end-systolic volume (from 69+/-26 to 60+/-28 mL; P=0.003), and unchanged end-diastolic volumes (122+/-34 versus 117+/-37 mL; P=NS). Infarct size, measured as late enhancement (LE) volume, decreased significantly, from 46+/-32 to 37+/-28 mL (P<0.05). There was a significant correlation between the reduction in LE volume and global ejection fraction improvement. The migratory capacity of transplanted cells as assessed ex vivo toward a gradient of vascular endothelial growth factor for CPCs and stromal cell derived factor-1 for BMCs was closely correlated with the reduction of LE volume. By multivariate analysis, migratory capacity remained the most important independent predictor of infarct remodeling.Analysis of serial contrast-enhanced MRI suggests that intracoronary infusion of adult progenitor cells in patients with AMI beneficially affects postinfarction remodeling processes. The migratory capacity of the infused cells is a major determinant of infarct remodeling, disclosing a causal effect of progenitor cell therapy on regeneration enhancement.
Use of Patient-Reported Outcomes to Improve the Predictive Accuracy of Clinician-Reported Adverse Events
Authors: E. Basch, A. Bennett, M. C. Pietanza
Journal: JNCI Journal of the National Cancer Institute (2011)

Abundant research has now demonstrated that patient and clinician reports of symptoms—and particularly symptomatic toxicities (ie, adverse events) during cancer treatment—provide discrepant yet complementary data (1–3). How can this be? Can’t only the patient or the clinician be “right”? The more patient-centered among us might state that the patient is always right by definition because nobody (not even the most sensitive clinician) can truly know another person’s subjective experience. But the more traditional among us might assert that clinicians should be considered right because they have an “objective” perspective based on experience and training, which prevents them from exaggerating or understating what they observe. In fact, it appears that both the patient and clinician provide information of value, which when combined provides a more accurate understanding of the patient’s symptoms. This finding is good news for those of us who are interested in improving the measurement of symptoms in clinical trials and practice. The optimistic among us might state that all we need to do now is figure out how to operationalize this approach.
Levocetirizine in the treatment of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study
Authors: E. Nettis, M.C. Colanardi, L. Barra, A. Ferrannini, A. Vacca, A. Tursi
Journal: British Journal of Dermatology (2005)

Background Chronic urticaria is a common skin condition. It is frequently a disabling disease because of the persistence of clinical symptoms, the unpredictable course and its negative influence on the quality of life. Objectives To determine whether levocetirizine is efficacious in the treatment of chronic idiopathic urticaria. Methods A randomized, double-blind, placebo-controlled study was conducted in 106 patients with a diagnosis of chronic idiopathic urticaria. A 1-week single blind placebo run-in period (baseline) was followed by a 6-week double blind active treatment period. The patients were randomized to receive one of the following treatments once daily: (a) oral levocetirizine 5 mg, or (b) oral placebo. The study ended after another 1-week single blind placebo washout period. Results The evaluable population consisted of 100 patients. Levocetirizine administered once daily is effective and well tolerated in the treatment of the symptoms of chronic idiopathic urticaria and in improving the patient's quality of life. Levocetirizine was superior to placebo in reducing the mean total symptoms score as well as individual symptoms, the number of daily episodes and the number of weals, the overall severity of symptoms and the quality of life. The significant beneficial effects of levocetirizine lasted only during the active trial, while at follow-up there was a significant worsening of all the variables evaluated in this study, after the end of the active trial (week 7). Conclusions A global assessment indicates that levocetirizine 5 mg once daily is an effective agent in patients with chronic idiopathic urticaria, as its action provides a rapid and satisfactory control of the symptoms and measures of subjective disease, although this is limited to the duration of treatment.
Two Decades of Declining Cancer Mortality: Progress with Disparity
Authors: Tim Byers
Journal: Annual Review of Public Health (2010)

The close of the twentieth century brought historic changes in cancer risk factors, early detection, and treatment. As a consequence, we have seen two decades of steadily declining risk of death from cancer in the United States. The reasons for declining cancer mortality rates are largely known: reduced tobacco use, the adoption of cancer early-detection methods, and better cancer therapeutics. Despite this progress, disparities in cancer mortality persist across different groups defined by race and social class. Because all the factors that account for declining cancer trends are influenced strongly by social class, and because of large social class disparities in cancer risk factors, there will likely be a widening gap in cancer mortality among those in lower socioeconomic groups in the future. This article reviews the trends in risk factors for cancer mortality and discusses the persistent problem of disparities by race and social class.
Activator of G Protein Signaling 3 Promotes Epithelial Cell Proliferation in PKD
Authors: Rama Nadella, Joe B. Blumer, Guangfu Jia, Michelle Kwon, Talha Akbulut, Feng Qian, Filip Sedlic, Tetsuro Wakatsuki, William E. Sweeney, Patricia D. Wilson, Stephen M. Lanier, Frank Park
Journal: Journal of the American Society of Nephrology (2010)

The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and autosomal dominant PKD. Increased AGS3 expression correlated with kidney size, which is an index of severity of cystic kidney disease. AGS3 expression localized exclusively to distal tubular segments in both normal and cystic kidneys. Short hairpin RNA-induced knockdown of endogenous AGS3 protein significantly reduced proliferation of cystic renal epithelial cells by 26 +/- 2% (P < 0.001) compared with vehicle-treated and control short hairpin RNA-expressing epithelial cells. In summary, this study suggests a relationship between aberrantly increased AGS3 expression in renal tubular epithelia affected by PKD and epithelial cell proliferation. AGS3 may play a receptor-independent role to regulate Galpha subunit function and control epithelial cell function in PKD.
Vascular repair by endothelial progenitor cells
Authors: A. Zampetaki, J. P. Kirton, Q. Xu
Journal: Cardiovascular Research (2008)

Accumulating evidence indicates the impact of endothelial progenitor cells (EPCs) in vascular repair. In patients, the number of EPCs is negatively correlated with the severity of atherosclerosis. In various animal models, transplantation of bone marrow-derived progenitor cells could sufficiently rescue organ function and enhance vascular repair and tissue regeneration. Increase in the number of circulating progenitors, induced by cell transfusion or enhanced mobilization, can also enhance restoration and integrity of the endothelial lining, suppress neointimal formation, and increase blood flow to ischaemic sites. However, the beneficial outcome of EPC infusion very much depends on the growth and differentiation factors within the tissue, cell-to-cell interactions, and the degree of injury. As highlighted by several studies, EPCs derive from different sources including bone marrow and non-bone marrow organs such as the spleen, the functional repair properties of which may vary with the maturation state of the cell. Thus, understanding the molecular mechanisms involved in EPC-repairing processes is essential. In the present review we focus on the role of EPCs in vascular diseases, and we provide an update on the mechanisms of EPC mobilization, homing, and differentiation.
The “reign of error” in social psychology: On the real versus imagined consequences of problem-focused research
Authors: Justin Kruger, Kenneth Savitsky
Journal: Behavioral and Brain Sciences (2004)

Krueger &amp; Funder (K&amp;F) make the familiar accusation that social psychologists focus too much on what people do wrong, rather than on what they do right. Although there is some truth to their charge, their accusations are overstated and their conclusions are incorrect. The field is far less problem-focused than they suggest, and the proposed consequences of this approach are more imagined than real.
Distinct Epidermal Growth Factor Receptor and <i>KRAS</i> Mutation Patterns in Non–Small Cell Lung Cancer Patients with Different Tobacco Exposure and Clinicopathologic Features
Authors: Issan Yee San Tam, Lap Ping Chung, Wai Sing Suen, Elaine Wang, May C.M. Wong, Kok Keung Ho, Wah Kit Lam, Shui Wah Chiu, Luc Girard, John D. Minna, Adi F. Gazdar, Maria P. Wong
Journal: Clinical Cancer Research (2006)

Abstract Purpose: This study evaluated the mutational profile of epidermal growth factor receptor (EGFR) and KRAS in non–small cell lung cancers in Hong Kong and determined their relation with smoking history and other clinicopathologic features. Experimental Design: Mutational profile of exons 18 to 21 of EGFR and codons 12, 13, and 61 of KRAS were determined in 215 adenocarcinomas, 15 squamous cell (SCC), and 11 EBV-associated lymphoepithelioma-like carcinomas (LELC). Results: EGFR mutations were prevalent in adenocarcinomas (115 of 215), uncommon in LELC (1 of 11), and not found in SCC (P &amp;lt; 0.001). Among adenocarcinomas, mutations were associated with nonsmokers (83 of 111; P &amp;lt; 0.001), female gender (87 of 131; P &amp;lt; 0.001), and well-differentiated (55 of 86) compared with poorly differentiated (11 of 41) tumors (P &amp;lt; 0.001). Decreasing mutation rates with increasing direct tobacco exposure was observed, with 74.8% (83 of 111) in nonsmokers, 61.1% (11 of 18) in passive, 35.7% (10 of 28) in previous, and 19.0% (11 of 58) in current smokers. There were 53% amino acid substitutions, 43% in-frame deletions, and 4% insertions. Complex patterns with 13% double mutations, including five novel substitutions, were observed. For KRAS, mutations occurred in adenocarcinoma only (21 of 215) and were associated with smokers (11 of 58; P = 0.003), men (14 of 84; P = 0.009) and poorly differentiated (7 of 41) compared with well-differentiated (4 of 86) tumors (P = 0.037). EGFR and KRAS mutations occurred in mutually exclusive tumors. Regression analysis showed smoking history was the significant determinant for both mutations, whereas gender was a confounding factor. Conclusion: This study shows EGFR mutations are prevalent in lung adenocarcinoma and suggests that it plays an increasing oncogenic role with decreasing direct tobacco damage.
Prognostic Significance of Renal Function in Elderly Patients with Isolated Systolic Hypertension
Authors: Peter W. de Leeuw, Lutgarde Thijs, Willem H. Birkenhäger, Sophia M. Voyaki, Aris D. Efstratopoulos, Robert H. Fagard, Gastone Leonetti, Choudomir Nachev, James C. Petrie, José L. Rodicio, Joseph J. Rosenfeld, Cinzia Sarti, Jan A. Staessen
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Several reports suggest that markers of renal function such as serum creatinine, serum uric acid, and urinary excretion of protein may be related to cardiovascular complications and mortality. This study analyzed the data from the Syst-Eur trial, which was a randomized, placebo-controlled, double-blind intervention trial in elderly patients with isolated systolic hypertension. The purpose was to evaluate whether serum levels of creatinine and uric acid and urinary protein excretion at entry are related to subsequent morbidity and mortality. Incidence rates of total mortality, cardiovascular mortality, stroke (fatal as well as nonfatal), coronary events, and all cardiovascular endpoints were calculated for each quintile of serum creatinine or serum uric acid or for each category of protein excretion (none, trace, and overt). Crude and adjusted relative hazard rates were also determined for each 20 μM increase in serum creatinine, each 50 μM increase in serum uric acid, and for each protein excretion category. Even when adjusted for age, gender, and various other covariates, serum creatinine was significantly associated with a worse prognosis. There was an U-shaped relationship between serum uric acid and total mortality, but otherwise no obvious relationships were detected between serum uric acid levels and complications when appropriate adjustments were made for confounding variables. Proteinuria at entry was a significant predictor of total mortality and all cardiovascular endpoints. It is concluded that higher levels of serum creatinine and trace or overt proteinuria are associated with an increased number of cardiovascular events and with a higher mortality in patients with isolated systolic hypertension.
Larger Cell Size in Rabbits With Heart Failure Increases Myocardial Conduction Velocity and QRS Duration
Authors: Rob F. Wiegerinck, Arie O. Verkerk, Charly N. Belterman, Toon A.B. van Veen, Antonius Baartscheer, Tobias Opthof, Ronald Wilders, Jacques M.T. de Bakker, Ruben Coronel
Journal: Circulation (2006)

Patients with heart failure (HF) have an increased QRS duration, usually attributed to decreased conduction velocity (CV) due to ionic remodeling but which may alternatively result from increased heart size or cellular uncoupling. We investigated the relationship between QRS width, heart size, intercellular coupling, and CV in a rabbit model of moderate HF and in computer simulations.HF was induced by pressure-volume overload. Heart weight (21.1+/-0.5 versus 10.2+/-0.4 g, mean+/-SEM; P<0.01) and QRS duration (58+/-1 versus 50+/-1 ms; P<0.01) were increased in HF versus control. Longitudinal CV (thetaL; 79+/-2 versus 67+/-4 cm/s; P<0.01) and transversal subepicardial CV (thetaT; 43+/-2 versus 37+/-2 cm/s; P<0.05) were higher in HF than in controls. Transmural CV (thetaTM) was unchanged (25+/-2 versus 24+/-1 cm/s; P=NS). Patch-clamp experiments demonstrated that sodium current was unchanged in HF versus control. Immunohistochemical experiments revealed that connexin43 content was reduced in midmyocardium but unchanged in subepicardium. Myocyte dimensions were increased in HF by approximately 30%. Simulated strands of mammalian ventricular cells (Luo-Rudy dynamic model) revealed increased thetaL and thetaT with increased myocyte size; however, increased CV could not compensate for increased strand size of longitudinally coupled cells, and consequently, total activation time was longer.Increased myocyte size combined with the observed expression pattern of connexin43 yields increased thetaL and thetaT and unchanged thetaTM in our nonischemic model of HF. A hypertrophied left ventricle together with insufficiently increased thetaL and unaltered thetaTM results in a prolonged QRS duration.
Weight and Blood Pressure
Authors: R. A. M. Scott
Journal: BMJ (1948)

Though information about the state of health of any section of the community is of particular value at the moment, few surveys of the nutrition of adults have been recorded.Some statistical records of haemoglobin levels are available, but little is known of the comparison, both in weight and in blood pressure, between age groups of people before the war and to-day.A review has been made of the weights and blood pressures of the male members of an office staff spread over the North of England.The table shows the age distribution of the men examined in 1938-9, 1943, and 1946-7.
Use of Genetic Testing by Employers
Authors: Richard J. McMurray
Journal: JAMA (1991)

OVER THE NEXT 15 YEARS, under the auspices of the federal government's "human genome project," scientists will try to map in detail each of the human cell's estimated 100 000 genes.<sup>1</sup>The knowledge derived from the project will enable physicians to detect an increasing number of diseases and predispositions for disease. It is expected that researchers will identify genes that contribute to the development of Alzheimer's disease, alcoholism, coronary artery disease, the different forms of cancer, and virtually every other illness.<sup>2</sup>In addition to enhancing the ability of physicians to diagnose disease, the knowledge from the genome project is expected to result in better preventive and therapeutic measures. For editorial comment see p 1835. Potential applications of information gained from the human genome project extend well beyond the setting of medical care. Employers, insurers, and law enforcement agencies all will have uses for genetic-testing techniques. In many cases,
Neuropsychological Decline in Schizophrenia From the Premorbid to the Postonset Period: Evidence From a Population-Representative Longitudinal Study
Authors: Madeline H. Meier, Avshalom Caspi, Abraham Reichenberg, Richard S.E. Keefe, Helen L. Fisher, HonaLee Harrington, Renate Houts, Richie Poulton, Terrie E. Moffitt
Journal: American Journal of Psychiatry (2013)

Despite the widespread belief that neuropsychological decline is a cardinal feature of the progression from the premorbid stage to the chronic form of schizophrenia, few longitudinal studies have examined change in neuropsychological functioning from before to after illness onset. The authors examined whether neuropsychological decline is unique to schizophrenia, whether it is generalized or confined to particular mental functions, and whether individuals with schizophrenia also have cognitive problems in everyday life.Participants were members of a representative cohort of 1,037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed prospectively to age 38, with 95% retention. Assessment of IQ and specific neuropsychological functions was conducted at ages 7, 9, 11, and 13, and again at age 38. Informants also reported on any cognitive problems at age 38.Individuals with schizophrenia exhibited declines in IQ and in a range of mental functions, particularly those tapping processing speed, learning, executive function, and motor function. There was little evidence of decline in verbal abilities or delayed memory, however, and the developmental progression of deficits in schizophrenia differed across mental functions. Processing speed deficits increased gradually from childhood to beyond the early teen years, whereas verbal deficits emerged early but remained static thereafter. Neuropsychological decline was specific to schizophrenia, as no evidence of decline was apparent among individuals with persistent depression, children with mild cognitive impairment, individuals matched on childhood risk factors for schizophrenia, and psychiatrically healthy individuals. Informants also noticed more cognitive problems in individuals with schizophrenia.There is substantial neuropsychological decline in schizophrenia from the premorbid to the postonset period, but the extent and developmental progression of decline varies across mental functions. Findings suggest that different pathophysiological mechanisms may underlie deficits in different mental functions.
PUERPERAL SEPSIS: AN INVESTIGATION REGARDING CONTAGION, AND THROAT CARRIERS OF THE STREPTOCOCCUS HAEMOLYTICUS
Authors: E. F. Murray
Journal: BMJ (1930)

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