tbuckley/cabot-search huggingface dataset:
Abstract 15899: Improvements in Cardiovascular Disease Risk Factors After Five Years of a Population-Based Intervention: The Heart of New Ulm Project
Authors: Abbey C Sidebottom, Arthur Sillah, David M Vock, Michael D Miedema, Raquel Pereira, Gretchen Benson, Jackie L Boucher, Thomas Knickelbine, Jeffery J VanWormer
Journal: Circulation (2014)

Objective:  We aimed to assess population-level changes in cardiovascular disease (CVD) risk factors over the first 5 years of The Heart of New Ulm Project (HONU).   Methods:  Started in 2009, HONU is a 10-year community intervention aimed at reducing modifiable CVD risk factors in rural New Ulm, MN. Interventions are delivered at all levels of the social ecological model through healthcare, worksite, and community settings. The community is served by one health system, enabling use of electronic health record (EHR) for ongoing CVD risk factor surveillance. EHR data was extracted for baseline (2008-2009) and two follow-up periods (2010-2011, 2012-2013) for residents age 40-79. Generalized estimating equations (GEE) were used to model the risk factors during the study period and account for within-subject correlation due to repeated measures. Covariates included time period, age, and gender. To examine changes stratified by baseline risk factor, analysis was limited to the cohort of individuals with data at baseline for each risk factor being examined.   Results:  Of the 7,855 residents in the target population, 92-97% had visits during at least one time period. In each time period, data availability for blood pressure (BP) was 88-96% and 55-67% for lipids. The proportion of residents with BP at goal (   Conclusion:  Significant improvement in BP and lipids were noted over 5 years in the HONU project. The bulk of these population-level improvements seem to be driven by better risk factor control among the sizeable number of individuals who were not at goal at baseline.
Gene Expression Profiling Allows Distinction between Primary and Metastatic Squamous Cell Carcinomas in the Lung
Authors: Simon G. Talbot, Cherry Estilo, Ellie Maghami, Inderpal S. Sarkaria, Duy Khanh Pham, Pornchai O-charoenrat, Nicholas D. Socci, Ivan Ngai, Diane Carlson, Ronald Ghossein, Agnes Viale, Bernard J. Park, Valerie W. Rusch, Bhuvanesh Singh
Journal: Cancer Research (2005)

Abstract Lung neoplasms commonly develop in patients previously treated for head and neck carcinomas. The derivation of these tumors, either as new primary lung cancers or as metastatic head and neck cancers, is difficult to establish based on clinical or histopathologic criteria since both are squamous cell carcinomas and have identical features under light microscopy. However, this distinction has significant treatment and prognostic implications. Gene expression profiling was performed on a panel of 52 sequentially collected patients with either primary lung (n = 21) or primary head and neck (n = 31) carcinomas using the Affymetrix HG_U95Av2 high-density oligonucleotide microarray. Unsupervised hierarchical clustering with Ward linkage and the Pearson correlation metric was performed. To assess robustness, bootstrap resampling was performed with 1,000 iterations. A t test of the normalized values for each gene was used to determine the genes responsible for segregating head and neck from lung primary carcinomas, and those with the most differential expression were used for later analyses. In the absence of a large “test” set of tumors, we used a supervised leave-one-out cross-validation to test how well we could predict the tumor origin. Once a gene expression profile was established, 12 lung lesions taken from patients with previously treated head and neck cancers were similarly analyzed by gene expression profiling to determine their sites of origin. Unsupervised clustering analysis separated the study cohort into two distinct groups which reliably remained segregated with bootstrap resampling. Group 1 consisted of 30 tongue carcinomas. Group 2 consisted of 21 lung cancers and 1 tongue carcinoma. The clustering was not changed even when normal lung or tongue profiles were subtracted from the corresponding carcinomatous lesions, and a leave-one-out cross-validation showed a 98% correct prediction (see Supplementary Data 1). A minimum set of 500 genes required to distinguish these groups was established. Given the ability to segregate these lesions using molecular profiling, we analyzed the lung tumors of undetermined origin. All cases clearly clustered with either lung or tongue tumor subsets, strongly supporting our hypothesis that this technique could elucidate the tissue of origin of metastatic lesions. Although histologically similar, squamous cell carcinomas have distinct gene expression profiles based on their anatomic sites of origin. Accordingly, the application of gene expression profiling may be useful in identifying the derivation of lung nodules and consequently enhances treatment planning.
Abstract 3262: Dynamic Left Ventricular Outflow Tract Obstruction In Patients Without Hypertrophic Cardiomyopathy
Authors: Kyung Jin Lee, Steve R. Ommen, David A. Foley, Jae K. Oh
Journal: Circulation (2007)

Background: Although dynamic left ventricular outflow tract (LVOT) obstruction is a hallmark for hypertrophic obstructive cardiomyopathy (HOCM), it can occur in other conditions. The aim of this study was to determine underlying conditions and clinical importance of LVOT obstruction in patients without HOCM. Methods: We reviewed the echocardiographic and clinical data of patients who underwent transthoracic echocardiography in Mayo Clinic Rochester from October 2001 to August 2006, and had LVOT peak pressure gradient (PG) &gt; 25mmHg at rest. Results: Of 719 patients identified, 159 (22 %) patients had dynamic LVOT obstruction without HOCM (77 men; mean age, 66.6 ± 12.9 years). Main presenting symptoms were chest pains in 95 (59.7 %), and dyspnea in 46 (28.9 %). LVOT PG was 51 ± 24 mmHg at rest and 68 ± 27 mmHg after provocation. In 114 (71.7 %) patients, early diastolic transmitral inflow velocity (E) and early diastolic mitral annular tissue velocity (Ea) were obtained. Mean E, Ea, and E/Ea were 105 ± 47 cm/s, 6.4 ± 5.7 cm/s, and 18.3 ± 11.0, respectively. Systolic anterior motion of mitral apparatus was observed in 100 (62.9 %) patients. Concentric increase in LV wall thickness or LVH was most common condition present in 57 patients (36%). The cause of LVH was hypertension in 40 (70.1%), aortic stenosis in 8 (14.0%), and chronic renal failure in 4 (7.0%). In these patients, major precipitating factors were hyperdynamic LV systolic function in 54 (94.7%), use of vasodilator in 34 (59.6%) and small LV cavity in 30 (52.6%). Other prominent associated conditions were basal septal hypertrophy, mitral valve repair, cardiac amyloid, and apical ballooning. There were 28 (17.6%) all-cause mortalities during follow up (25 ± 17 months) including malignancy in 6 (21.4 %), sudden cardiac deaths in 4 (14.3 %), congestive heart failure in 3 (10.7 %). Conclusions: Dynamic LVOT obstruction can be found in patients without HOCM. The most common condition to develop dynamic LVOT obstruction without HOCM, is concentric increase in LV wall thickness in the setting of hyperdynamic motion, small LV cavity, and use of vasodilator. Other conditions which predispose patients for dynamic LVOT obstruction are hypovolemia, cardiac amyloidosis, apical ballooning syndrome, and mitral valve repair.
An analysis of the attrition of drug candidates from four major pharmaceutical companies
Authors: Michael J. Waring, John Arrowsmith, Andrew R. Leach, Paul D. Leeson, Sam Mandrell, Robert M. Owen, Garry Pairaudeau, William D. Pennie, Stephen D. Pickett, Jibo Wang, Owen Wallace, Alex Weir
Journal: Nature Reviews Drug Discovery (2015)
Energy expenditure during daily activities as measured by two motion sensors in patients with COPD
Authors: Vinícius Cavalheri, Leila Donária, Thiemi Ferreira, Matheus Finatti, Carlos Augusto Camillo, Ercy Mara Cipulo Ramos, Fabio Pitta
Journal: European Respiratory Journal (2011)

Background:  In patients with chronic obstructive pulmonary disease (COPD), energy expenditure (EE) assessment during the performance of daily activities is not yet studied in depth. The aim of this study was to determine which daily activities are more demanding to patients with COPD and to compare the accuracy of EE estimation given by the pedometer Digiwalker SW701 (DW) and the multisensor SenseWear Armband (SAB).   Methods:  Thirty-six patients with COPD (20 men; FEV 1  48±15%predicted; BMI 25.7±8 kg/m 2 ) were submitted to a modified version of the Glittre ADL-test, which included five activities performed for one minute each: walking on the level, walking on the level carrying a backpack, walking up/downstairs, rising/sitting in chairs and moving objects in and out of a shelf. During the protocol subjects wore both devices concomitantly, and indirect calorimetry (IC) was simultaneously performed as the criterion method to assess EE.   Results:  The most demanding daily activity for individuals with COPD was walking up/downstairs (4.9±1.7Kcal  versus  3.7±1.4 to 4.2±1.8Kcal for the other tasks; p versus  IC=21±8Kcal; p>0.05), although overestimation was found in activities involving walking. DW showed significant EE underestimation in the sum of the activities (9.6±4.3Kcal; p versus  IC) and for each activity.   Conclusion:  Walking up/downstairs was the most energy-demanding daily activity for patients with COPD. Furthermore, during daily activities, the multisensor showed adequate overall estimation of energy expenditure, as opposed to the pedometer.
Triage of back pain by physiotherapists in orthopaedic clinics
Authors: C R Weatherley, P G Hourigan
Journal: Journal of the Royal Society of Medicine (1998)

In 1994 we described a system whereby certain patients with back pain, on referral to an orthopaedic clinic, were seen first by a physiotherapist who referred on only the problem cases and those in need of surgery ('triage'). This practice has grown rapidly but there have been difficulties. To clarify these we have carried out a postal questionnaire. The results reveal similar practices in most centres but some discrepancies that are cause for concern. These relate to the workload of the physiotherapist, informed consent, supervision and accountability, the type of cases seen and not least the stresses on the physiotherapist. We believe the triage system has many benefits, but if it is not to be derailed the issues of concern must be addressed and the posts properly structured.
Practice- and Community-Based Interventions to Increase Human Papillomavirus Vaccine Coverage
Authors: Linda M. Niccolai, Caitlin E. Hansen
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Vaccines against human papillomavirus (HPV) are recommended for routine use in adolescents aged 11 to 12 years in the United States, but uptake remains suboptimal. Educational interventions focused on parents and patients to increase coverage have not generally demonstrated effectiveness. <h3>Objective</h3> To systematically review the literature on effectiveness of interventions conducted at the practice or community level to increase uptake of HPV vaccines in the United States. <h3>Evidence Review</h3> Keyword searches of the PubMed, Web of Science, and MEDLINE databases identified studies of adolescents that included the outcome of HPV vaccination published through July 2014. References of identified articles were also reviewed. A total of 366 records were screened, 38 full-text articles were reviewed, and 14 published studies were included. Results were summarized by different intervention approaches. <h3>Findings</h3> Practice- and community-based intervention approaches included reminder and recall (n = 7), physician-focused interventions (eg, audit and feedback) (n = 6), school-based programs (n = 2), and social marketing (n = 2) (2 interventions tested multiple approaches). Seven studies used a randomized design, and 8 used quasiexperimental approaches (one used both). Thirteen studies included girls, and 2 studies included boys. Studies were conducted in a variety of populations and geographic locations. Twelve studies reported significant increases in at least one HPV vaccination outcome, one reported a nonsignificant increase, and one reported mixed effects. <h3>Conclusions and Relevance</h3> Most practice- and community-based interventions significantly increased HPV vaccination rates using varied approaches across diverse populations. This finding is in stark contrast to a recent review that did not find effects to warrant widespread implementation for any educational intervention. To address the current suboptimal rates of HPV vaccination in the United States, future efforts should focus on programs that can be implemented within health care settings, such as reminder and recall strategies and physician-focused efforts, as well as the use of alternative community-based locations, such as schools.
Occult Manifestations of Cancer
Authors: R D HENDERSON
Journal: JAMA (1963)

Clinical syndromes occasionally associated with or heralding cancer are summarized and classified.Some tumours present with manifestations of an endocrine or endocrine-like action; included in this group are thymomas, non-beta-cell tumours of the pancreas and carcinoids. Cushing's syndrome, hypoglycemia, hypercalcemia, polycythemia and gynecomastia have been produced by a wide variety of tumours. Tumour emboli, non-bacterial thromboendocarditis and thrombophlebitis occasionally occur, but thrombophlebitis is not so frequent as was previously considered. Neurological syndromes are rare and show a great variety of presentations. Other occult manifestations of cancer include hypertrophic pulmonary osteoarthropathy, various skin diseases, obscure pyrexias and, in Hodgkin's disease, pain secondary to alcohol consumption.
Commentary: Wide angle thinking helps patients with distressing illness
Authors: Ed Peile
Journal: BMJ (2006)

Kenneth Neville presents interesting problems for specialists and generalists alike.1 At the time of the case presentation, we were told about a young man with distressing symptoms of postprandial vomiting leading to weight loss and weakness. The local hospital had diagnosed gastro-oesophageal reflux disease, and a battery of other routine investigations had given negative results. We were presented with several possibly relevant psychological factors, and it was mentioned that his asthma had been difficult to control. Readers were invited to consider the differential diagnosis and to suggest the most helpful course of management for the family doctor to take when …
The role of the IGF system in T-lymphocyte activation
Authors: Gila Idelman, Gabriella Rustici, Adriana DeSiervi, Quentin Li, Idalia Montano, Cynthia Haggerty, Dennis Taub, Kevin Gardner
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

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The process of T-cell costimulation is a critical process in the immune response that influences T-cell proliferation, cytokine production and survival. Classically it involves the activation of cell surface molecules that alone are incapable of activating T-cells but rather amplify or repress molecular signals generated by the T-cell Receptor (TCR). In this study we provide evidence that IGF-/IGF-1 receptor (IGF-IR) axis represents a true costimulatory system in human T-cells. The IGF-1 system is a well characterized stimulator of cell growth, differentiation, and tumor progression and “cross-talks” with a wide range of other receptors. The interplay between the IGF-1 system and elements of T cell activation machinery is less understood. Our data show significant costimulating effects of IGF on proliferation of primary mouse and human T-cells. It increases IL-2 production, proliferation and viability of CD3+ cells in response to stimulating agents and costimulates cytotoxicity of CD8+ cells. We show that IGF-1 driven regulation is dependent on the differentiation state of the cell and has influence on both cytokine gene and immediate early gene expression. Major intracellular targets and pathways through which IGF-1 acts in synergy with TCR-derived signals involve Akt, ERK, NF-kappa B and CREB activation. Increased levels of IGF-I mRNA in CD3/CD28/IGF-1 stimulated PBMC cells provides evidence of an inducible autocrine regulation. We present evidence that the lymphoid oncogene TPL2 is an important target for IGF-1 in activated T-cells and transformed leukemia cells, suggesting a possible oncogenic linkage between elevated IGF-1 expression and lymphoid malignancies. Finally, we propose that TPL2 is a key regulator of a feedforward network motif in control of secondary effectors (JNK, MEK, Fos etc) that influence a common set of target genes. Since both regulators are positive this loop will provides a sustained signal to promote T-cell proliferation and cytokine production. In conclusion, our data demonstrate a close involvement of the IGF-I/IGF-IR axis in the complex processes of T-cell activation, proliferation and survival; thereby implicating a major role for IGF-1 in both T-cell homeostasis and tumor progression.
The effect of antiphlogistic-corticoid conditioning (the "A-CC effect") upon the Walker tumor.
Authors: Hans Selye
Journal: Cancer Research (1955)

Experiments on intact albino rats have shown that small doses of cortisol, given conjointly with small amounts of ammonium chloride (an “antiphlogistic-corticoid conditioning” substance), failed to influence either the growth or the exudate-forming ability of Walker tumor 256 transplants in the granuloma pouch.

In adrenalectomized rats, treatment with these same substances, at the same dose levels, caused pronounced retardation of tumor growth and inhibition of exudate formation, under otherwise identical conditions.

The experiments suggest that the antineoplastic and anti-exudative effect of cortisol, administered in conjunction with a sensitizing substance such as NH4Cl, is suppressed by the adrenals, perhaps through the compensatory secretion of a cortisolantagonistic steroid.
Profound hypoglycemia with the addition of a tricyclic antidepressant to maintenance sulfonylurea therapy [published erratum appears in Am J Psychiatry 1987 Nov;144(11):1521]
Authors: B L True, P J Perry, E A Burns
Journal: American Journal of Psychiatry (1987)

Cases of profound hypoglycemia after the initiation of tricyclic antidepressant therapy in two patients taking sulfonylureas are described. To the authors' knowledge, this is the first report of a potential drug interaction between tricyclic antidepressants and sulfonylureas.
Abstract P348: Lower Odds of Post-Stroke Depression Among Hispanics in New York City: Findings From the Stroke Warning Information and Faster Treatment (SWIFT) Study
Authors: Emily Goldmann, Eric Roberts, Nina Parikh, Heather M Kuczynski, Bernadette Boden-Albala
Journal: Circulation (2015)

Introduction: Post-stroke depression (PSD) is common and associated with poor stroke outcomes, lower quality of life, and higher health care costs. Few studies have examined race/ethnic disparities in PSD, with inconsistent findings. Characteristics of social networks - which may differ by race/ethnicity and influence mental health outcomes - have not been investigated as explanations for race/ethnic disparities in PSD. Hypothesis: Having larger social networks explains the protective effect of Hispanic ethnicity on PSD. Methods: As part of SWIFT, mild/moderate stroke and TIA patients were prospectively enrolled in an educational intervention aimed at action around acute stroke symptoms. Depressive symptoms were assessed as part of a larger neurological and psychosocial battery in 1,014 individuals hospitalized for stroke/TIA in upper Manhattan using the CES-D scale. CES-D scores ≥ 8 indicated any depression (8-15 = minor depression, ≥ 16 = depression). Both minor depression and depression were assessed g...
GS-101 Antisense Oligonucleotide Eye Drops Inhibit Corneal Neovascularization
Authors: Claus Cursiefen, Felix Bock, Folkert K. Horn, Friedrich E. Kruse, Berthold Seitz, Vincent Borderie, Beatrice Früh, Michael A. Thiel, Frank Wilhelm, Bernard Geudelin, Isabelle Descohand, Klaus-Peter Steuhl, Angela Hahn, Daniel Meller
Journal: Ophthalmology (2009)
Abstract 19452: Prrx1 Interacts with and Inhibits Pitx2 Function
Authors: Elena Dolmatova, Rebecca R Cooper, Patrick T Ellinor
Journal: Circulation (2012)

Background: Genome-wide association studies have identified 9 genomic loci associated with atrial fibrillation (AF) two of which are located at chromosomes 4q25 and 1q24 near the genes PITX2 and PRRX1 respectively. Pitx2 is crucial for the heart development and its loss leads to the inducible AF in mice. Since Prrx1 is a transcriptional co-activator we hypothesized that it may interact with and modulate Pitx2 function. Methods: We assessed the expression pattern of Pitx2 and Prrx1 in mouse atria by qPCR. Using an in vitro overexpression system we tested if Prrx1 and Pitx2 are present in a complex via co-immunoprecipitation studies (co-IP). We then made serial deletion constructs to determine the site of Prrx1 interaction with Pitx2. We assessed functional consequences of this interaction by siRNA knock-down followed by qPCR and luciferase reporter assays on the Prrx1, ANF, and HCN4 promoters. Results: Pitx2 and Prrx1 had a similar expression pattern in adult mouse atria with a 3.4±0.85 fold overexpression for Pixt2 and 1.7±0.55 fold for Prrx1 in LA, compared to RA (p&lt;0.05). Our co-IP data show that Prrx1 and Pitx2 are present in a complex with binding site located at the homeodomain of Pitx2 (aa72-92, aa119-139, and aa131-151 for Pitx2a, Pitx2b and Pitx2c respectively). SiRNA knockdown studies in atrial cell line showed that knockdown of Pitx2 reduced Prrx1 expression by 71±29% (p&lt;0.05) and Pitx2 knockdown reduced Prrx1 expression by 56±21% (p&lt;0.05). Prrx1 but not Pitx2 knockdown caused 68±29% and 65±28% reduction in HCN4 and ANF mRNA levels respectively. All Pitx2 isoforms activated Prrx1 promoter by 4.3±2.7 fold in luciferase reporter assay, and this effect was abolished by addition of Prrx1 (p&lt;0.05). Similar results were seen with ANF promoter: Pitx2 increased promoter activity by 2.2±0.2 fold, and addition of Prrx1 brought it back to baseline (p&lt;0.05). In contrast, neither Prrx1, nor Pitx2 had significant effect on HCN4 promoter activity. Conclusions: Our data show that in vitro Prrx1 and Pitx2 are present in a complex. Further, we demonstrate that Prrx1/Pitx2 interaction has functional consequences that alter expression of some atria-specific genes. Thus, the Prrx1/Pitx2 interaction may be an interesting regulatory mechanism in the susceptibility to the AF.