tbuckley/cabot-search huggingface dataset:
Abstract 9613: Randomized Evaluation of Anacetrapib Lipid-Modifying Therapy in Patients With HeteroZygous Familial HypercholesterolEmia (REALIZE Study)
Authors: John J Kastelein, Joost Besseling, Sukrut Shah, Jean Bergeron, Gisle Langslet, G Kees Hovingh, Naab Al-Saady, Michiel Koeijvoets, John Hunter, Amy O Johnson-Levonas, Jennifer Fable, Aditi Sapre, Yale Mitchel
Journal: Circulation (2014)

Introduction: Anacetrapib, a cholesteryl ester transfer protein inhibitor, has been shown to robustly reduce atherogenic lipoproteins including low-density lipoprotein cholesterol (LDL-C), Apo B and raise high-density lipoprotein cholesterol (HDL-C) as well as ApoA1. Hypothesis: This 1-year, Phase 3, multicenter, randomized, double-blind, placebo-controlled study assessed the lipid-modifying efficacy and safety profile of anacetrapib added to optimized LDL-C lowering therapy in patients with heterozygous familial hypercholesterolemia (HeFH). Methods: Patients with a genotype-confirmed or clinical diagnosis of HeFH, treated with an optimal dose of statin ± other lipid-modifying medication(s) and having an LDL-C ≥100 mg/dL without history of cardiovascular disease or LDL-C ≥70 mg/dL with a history of CVD were randomized in a ratio of 2:1 to anacetrapib 100 mg (n=204) or placebo (n=102) for 52 weeks followed by a 12-week reversal phase. The primary end points were the percent change from baseline in LDL-C (beta-quantification method) and the safety profile of anacetrapib. This trial is registered in ClinicalTrials.gov, #NCT01524289. Results: A total of 306 patients were enrolled at 25 sites in 9 countries. At baseline, most patients were on high-dose statin therapy and &gt;70% also were on ezetimibe. Baseline LDL-C and HDL-C were 129.4 and 53.3 mg/dL, respectively. At Week 52, anacetrapib vs. placebo significantly reduced LDL-C by 39.7% and increased HDL-C by 102.1% (p&lt;0.001 for both). Significant placebo-adjusted reductions in Apo B (24.8%) and increases in Apo A-I (32.9%) also were observed. Significantly more patients in the anacetrapib vs. placebo group achieved LDL-C &lt;100 (82% vs. 18%; p&lt;0.001) and &lt;70 mg/dL (44% vs. 5%; p&lt;0.001). Sustained effects on LDL-C (21.9%; p&lt;0.001) and HDL-C (53.0%; p&lt;0.001) were seen 12-weeks after cessation of anacetrapib therapy. No clinically important between-group differences were seen in the proportions of patients with abnormalities in liver enzymes, CK, blood pressure, electrolytes, adverse experiences and adjudicated CV events. Conclusion: In patients with HeFH, treatment with anacetrapib for 1 year was generally well tolerated and resulted in substantial reductions in LDL-C and increases in HDL-C.
Association of premorbid intellectual function with cerebral metabolism in Alzheimer's disease: implications for the cognitive reserve hypothesis
Authors: Gene E. Alexander, Maura L. Furey, Cheryl L. Grady, Pietro Pietrini, Daniel R. Brady, Marc J. Mentis, Mark B. Schapiro
Journal: American Journal of Psychiatry (1997)

Clinical heterogeneity in Alzheimer's disease has been widely observed. One factor that may influence the expression of dementia in Alzheimer's disease is premorbid intellectual ability. It has been hypothesized that premorbid ability, as measured by educational experience, reflects a cognitive reserve that can affect the clinical expression of Alzheimer's disease. The authors investigated the relation between estimates of premorbid intellectual function and cerebral glucose metabolism in patients with Alzheimer's disease to test the effect of differing levels of premorbid ability on neurophysiological dysfunction.In a resting state with eyes closed and ears occluded, 46 patients with Alzheimer's disease were evaluated with positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose to determine cerebral metabolism. Premorbid intellectual ability was assessed by a demographics-based IQ estimate and performance on a measure of word-reading ability.After the authors controlled for demographic characteristics and dementia severity, both estimates of premorbid intellectual ability were inversely correlated with cerebral metabolism in the prefrontal, pre-motor, and left superior parietal association regions. In addition, the performance-based estimate (i.e., reading ability) was inversely correlated with metabolism in the anterior cingulate, paracentral, right orbitofrontal, and left thalamic regions, after demographic and clinical variables were controlled for.The results suggest that higher levels of premorbid ability are associated with greater pathophysiological effects of Alzheimer's disease among patients of similar dementia severity levels. These findings provide support for a cognitive reserve that can alter the clinical expression of dementia and influence the neurophysiological heterogeneity observed in Alzheimer's disease.
Abstract 13584: Can Family History of Sudden Death Predict a Risk for Ventricular Fibrillation in Patients With Brugada Syndrome?
Authors: Hiroshi Morita, Satoshi Nagase, Hironobu Nishii, Koji Nakagawa, Akira Ueoka, Akihito Miyoshi, Motoki Kubo, Hiroshi Ito
Journal: Circulation (2014)

Introduction: Some reports showed that plural number of patients within a family of the Brugada syndrome (BrS) suffered from VF and family history (FH) of sudden death (SD) seems to be an important risk marker for VF. However, recent reports failed to show its predictive value for the occurrence of cardiac events in patients with BrS. Here, we evaluated incidence and situation of SD victims of the family member of the patients with BrS and examined its significance on subgroups of the patients. Methods: We evaluated the incidence of FH of SD in 362 patients with BrS (246 asymptomatic patients [Asymptomatic group], 97 patients with syncope [Syncope group] and 19 patients with VF [VF group]). We analyzed situation and the potent risk factors at the setting of SD in victims. Results: Ninety-eight patients with BrS (27%) had 126 victims of SD in their families (111 males, age at SD 48 ± 11yrs.). Incidence of FH of SD was not different in each patient subgroup (Asymptomatic: 27%, Syncope: 28%, VF: 21%). Most o...
Science education and communication
Authors: Dennis Ausiello
Journal: Journal of Clinical Investigation (2007)

Since its inception, members of the Association of American Physicians (AAP) have made distinguished contributions as physician-scientists, educators, and clinicians. I would like to speak to you today about two intersecting missions of our Society and profession that I am personally passionate about, and believe require serious stewardship: science education for the development of the physician-scientist, and the important parallel activity of communication to our public and Congress about science and the process of discovery.
Role of ICAM-2 in neutrophil transepithelial migration in the lung
Authors: Carine Rebeyrol, Joanna C. Porter
Journal: European Respiratory Journal (2012)

Many inflammatory diseases of airways including COPD and cystic fibrosis are characterized by migration of neutrophils from the interstitium across the respiratory epithelium into the airspaces. Neutrophil transepithelial migration (egression) across the bronchial epithelial cell (BEC) barrier promotes resolution of inflammation, whereas movement across the alveolar epithelial cell (AEC) barrier, often required for pathogen control, may prove detrimental to the human and resulting lung injury.  We have shown that intercellular adhesion molecule (ICAM)-2 is required for leukocyte migration across the bronchial epithelium. We have then used immunohistochemistry (IHC), to show that although ICAM-2 is expressed on the bronchial epithelium there is very little expression on the alveolar epithelium in normal human lung. Our hypothesis is that egression of neutrophils across the bronchial and alveolar epithelia are differentially regulated, and that understanding these processes is essential to develop effective ways to promote safe resolution of inflammation.  Primary human (h)BECs and AECs are grown at air liquid interface on Transwell™ collagen coated polyester membranes. Then, the cells are stimulated with pro-inflammatory mediators (TNF-α, TGF-β, LPS) for 4h or 24h. IHC, qRT-PCR, western blot and flow cytometry assays of ICAM-2 are performed. The role of ICAM-2 in neutrophil migration across hBEC and hAEC monolayers in the physiological basal to apical direction is observed.  Our results establish the role of ICAM-2 in regulating neutrophil-epithelial interactions in the lung and the central role of this molecule in the resolution of inflammation.
Biomarkers of an Autoimmune Skin Disease—Psoriasis
Authors: Shan Jiang, Taylor E. Hinchliffe, Tianfu Wu
Journal: Genomics Proteomics & Bioinformatics (2015)

Psoriasis is one of the most prevalent autoimmune skin diseases. However, its etiology and pathogenesis are still unclear. Over the last decade, omics-based technologies have been extensively utilized for biomarker discovery. As a result, some promising markers for psoriasis have been identified at the genome, transcriptome, proteome, and metabolome level. These discoveries have provided new insights into the underlying molecular mechanisms and signaling pathways in psoriasis pathogenesis. More importantly, some of these markers may prove useful in the diagnosis of psoriasis and in the prediction of disease progression once they have been validated. In this review, we summarize the most recent findings in psoriasis biomarker discovery. In addition, we will discuss several emerging technologies and their potential for novel biomarker discovery and diagnostics for psoriasis.
Cadherin switch from E- to N-cadherin in melanoma progression is regulated by the PI3K/PTEN pathway through Twist and Snail
Authors: L. Hao, J.R. Ha, P. Kuzel, E. Garcia, S. Persad
Journal: British Journal of Dermatology (2012)

Transition of normal melanocytic cells to malignant melanoma has characteristic features of epithelial to mesenchymal transition. This includes the disruption of the adherens junctions caused by the downregulation of E-cadherin and the upregulation of N-cadherin. The cadherins have functional importance in normal skin homeostasis and melanoma development; however, the exact mechanism(s) that regulate the 'cadherin switch' are unclear.To determine the mechanistic role of the PI3K/PTEN pathway in regulating the change in cadherin phenotype during melanoma progression.Using a panel of cell lines representative of the phases of melanoma progression, we determined cellular expressions of the components of the PI3K/PTEN pathway, E- and N-cadherin, and the transcriptional regulators Twist, Snail and Slug with Western blot and immunofluorescence analysis. Transcriptional regulation of E-cadherin, N-cadherin, Twist and Snail by the PI3K/PTEN pathway was confirmed using quantitative reverse transcription-polymerase chain reaction.Loss or inactivity of PTEN correlated with the switch in cadherin phenotype during melanoma progression. PTEN-null or inactive cells exhibited high levels of phosphorylated protein kinase B (PKB)/AKT (Serine 473) (PKB-Ser473-P), undetectable levels of E-cadherin and high levels of N-cadherin. Re-introduction of PTEN or treatment with the PI3K inhibitor Wortmannin resulted in the re-expression of E-cadherin and downregulation of N-cadherin. This cadherin switch was regulated at the transcriptional level by Twist and Snail which were, in turn, transcriptionally regulated by the PI3K pathway. Although E-cadherin was re-expressed, it failed to localize to the plasma membrane.The PI3K/PTEN pathway transcriptionally regulates the 'cadherin switch' via transcriptional regulation of Twist and Snail but does not regulate the localization of E-cadherin to the plasma membrane.
T-Cell–Depleted Allogeneic Bone Marrow Transplantation as Postremission Therapy for Acute Myelogenous Leukemia: Freedom From Relapse in the Absence of Graft-Versus-Host Disease
Authors: Esperanza B. Papadopoulos, Matthew H. Carabasi, Hugo Castro-Malaspina, Barrett H. Childs, Stephen Mackinnon, Farid Boulad, Alfred P. Gillio, Nancy A. Kernan, Trudy N. Small, Paul Szabolcs, Joanne Taylor, Joachim Yahalom, Nancy H. Collins, Sharon A. Bleau, Patricia M. Black, Glenn Heller, Richard J. O' Reilly, James W. Young
Journal: Blood (1998)
Abstract 4626: Neurological and Cognitive Function After Percutaneous Transapical Aortic Valve Implantation With the Edwards SAPIEN™ Stent Valve Bioprosthesis
Authors: Stephan C Knipp, Sabrina Lueck, Jan F Fritsch, Daniel Jokisch, Marc Schlamann, Matthias Thielmann, Philipp Kahlert, Holger Eggebrecht, Markus Kamler, Hans C Diener, Raimund Erbel, Heinz Jakob
Journal: Circulation (2009)

Objective: Transapical transcatheter aortic valve implantation (TA-TAVI) is a reasonable alternative to open heart surgery for the treatment of severe aortic valve stenosis in surgical high-risk pa...
Evaluation of the Legionella V-TesT compared to the BinaxNOW to detect Legionella serogroup 1 antigen in urine samples
Authors: Evy De Witte, Katherine Loens, Christine Lammens, Jordy Almirall, Herman Goossens, Greet Ieven
Journal: European Respiratory Journal (2011)

The performance and user friendliness of a new immunochromatographic assay, the Legionella V -tesT (Coris Bioconcept) for the detection of Legionella pneumophila serogroup 1 antigen in urine (uAg) were evaluated by comparing its results with the BinaxNOW Legionella uAg-test results (Inverness Medical).

For direct uAg testing using both tests, 129 previously collected and frozen urine samples were used: 61 specimens from pneumonia patients during a Legionella outbreak: 34 from the Hospital of Matarό (Spain), 27 from the outbreak in Kapellen (Belgium, 1999) and 68 urine samples from patients with lower respiratory tract infections other than Legionella infections enrolled in the European GRACE study. In case of discrepant results, urine samples were tested with the Biotest. Results of culture and/or PCR on respiratory samples were included to conclude on the true positive status of the patient. The number of manipulations and the turn around time (TAT) were evaluated as well.

41/129 (32%) samples tested were BinaxNOWpositive. The sensitivity and specificity of the V -TesT in comparison to the BinaxNOW were 97.6% and 97.7% respectively.

View this table:

Results for the evaluation of the V-tesT in comparison to the BinaxNOW Legionella 





Results yielded 2 apparent false positives and 1 false negative: all were confirmed as true positive Legionella infections. The TAT was comparable but the new V -TesT could be used directly on the urine specimen, while the BinaxNOW required two additional steps.

The V -TesT has comparable performance characteristics to the BinaxNOW Legionella and is an even more user-friendly test.
Abstract P114: Low Prevalence of Ideal Cardiovascular Health Metrics among African Americans: The Jackson Heart Study
Authors: Luc Djousse, Andrew Petrone, Chad Blackshear, Michael Griswold, Jane Harman, Cheryl Clark, Sameera Talegawkar, Jiankang Liu, DeMarc Hickson, J Gaziano, Patricia Dubbert, Adolfo Correa, Katherine Tucker, Herman Taylor
Journal: Circulation (2014)

Background: While the prevalence of cardiovascular health metrics or Life’s Simple Seven (LSS) has been shown to be far from optimal in the US, such information has been predominantly reported in Caucasians. The burden of cardiovascular disease among African Americans underscores the need to evaluate the prevalence and secular trends of LSS in other ethnic groups. Objective: To test the hypothesis that the prevalence of the LSS is far from ideal among participants of the Jackson Heart Study. Methods: We analyzed LSS with 3,500 African Americans from the Jackson Heart Study, using data from their first clinic visit (2000-2004). Standard methods were used to measure blood pressure, glucose, body mass index (BMI), and cholesterol. Information on physical activity, smoking, and diet was collected with interviewer-administered questionnaires. Each of the LSS metrics (smoking status, diet, physical activity, BMI, fasting blood glucose, total cholesterol, and blood pressure) was categorized as poor, intermediate, or ideal, as defined by the AHA guidelines. Results: The mean age at baseline was 56.9 ± 12.2 years and 2,350 participants (67%) were women. Among men, the prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal cardiovascular health metrics was 6.6%, 25.8%, 32.7%, 21.6%, 10.6%, 2.3%, 0.4%, and 0%, respectively. Corresponding values for women were 3.2%, 28.1%, 32.9%, 22.3%, 10.1%, 2.9%, 0.38%, and 0%. While about two-thirds of men and women reported ideal smoking status, almost none reported ideal diet quality, and few met recommendations for BMI and blood pressure ( Figure) . Conclusions: Our data are consistent with less than optimal prevalence of cardiovascular health metrics in both men and women from the Jackson Heart Study. The lower prevalence of meeting ideal recommendations for diet, physical activity, BMI, and blood pressure underscores the need for targeted interventions to improve these modifiable lifestyle factors in order to reduce the burden of cardiovascular disease among African-Americans.
Assessment of mis-beliefs about bronchial asthma
Authors: Gauri Gadge, Tushar Sahasrabudhe
Journal: European Respiratory Journal (2013)

Patient education is an integral part of asthma care. It is important to know the prevalent beliefs in the society so that the common misconceptions can be clarified in education sessions. Hence a questionnaire based study about asthma was conducted. The questionnaire was developed in local languages and was self-filled by total 100 asthma patients. A total of 54 beliefs about causes, diagnosis and treatment of asthma were evaluated. The analysis brought out some critical misconceptions about asthma. 27% believed that asthma is contagious and 86% believed that it is transmitted by coughing. 38% did not know the difference between allergen and triggers of asthma. 69% did not feel any need to evaluate for asthma if they had allergic rhinitis. 87% felt that asthma can be diagnosed with X-ray or blood tests and only 15% knew about spirometry. 49% felt that tablets are the main treatment of asthma. 38% believed that alternative medicine is a validated treatment for asthma. 35% believed that regular preventive treatment for asthma may lead to growth retardation of children. 63% believed that getting free from symptoms mean cure of asthma and 91% were not comfortable to continue asthma treatment when symptom free. 50% believed that limitation of activities and diet restrictions are necessary for asthma control. Also, 59% patients believed that inhalers cause dependency and hence should be avoided. The study highlights a large gap between the recommended asthma treatment and the ground reality in a developing country. Tremendous efforts and regular patient education on large scale is required. Some mis-beliefs were communicated to patients by the doctors and hence they also need training. Use of spirometry needs to be encouraged.
Effect of Darbepoetin Alfa on Exercise Tolerance in Anemic Patients With Symptomatic Chronic Heart Failure
Authors: Piotr Ponikowski, Stefan D. Anker, Joanna Szachniewicz, Darlington Okonko, Mark Ledwidge, Robert Zymlinski, Enda Ryan, Scott M. Wasserman, Nigel Baker, Dylan Rosser, Stuart D. Rosen, Philip A. Poole-Wilson, Waldemar Banasiak, Andrew J.S. Coats, Ken McDonald
Journal: Journal of the American College of Cardiology (2007)
Obstetric complications and age at onset in schizophrenia: an international collaborative meta-analysis of individual patient data
Authors: H Verdoux, J R Geddes, N Takei, S M Lawrie, P Bovet, J M Eagles, R Heun, R G McCreadie, T F McNeil, E O'Callaghan, G Stöber, M U Willinger, P Wright, R M Murray
Journal: American Journal of Psychiatry (1997)

An excess of obstetric complications in the histories of schizophrenic patients is a well-replicated finding, but less consistent results have been found concerning the relationships between obstetric complications and family history of schizophrenia, age at onset of schizophrenia, and gender. Small sample size limited the power of previous studies that attempted to assess such relationships. The aim of this study was to use data on individual patients from all available studies to examine the links between a history of obstetric complications and family history of schizophrenia, age at onset, and gender.Raw data from 854 schizophrenic patients concerning history of obstetric complications rated according to the Lewis and Murray scale were obtained from 11 different research groups. Weighted average estimates were calculated with the use of regression techniques.A significant association was found between age at onset of schizophrenia and obstetric complications: the earlier the age at onset, the more likely the history of obstetric complications. Subjects with onset of schizophrenia before age 22 were 2.7 times more likely than those with onset at a later age to have had a history of abnormal presentation at birth and 10 times more likely to have had a history of complicated Cesarean birth. No association was found between obstetric complications and family history of schizophrenia or gender.The association between obstetric complications and early age at onset of schizophrenia indicates that the pathophysiology of early-onset schizophrenia involves neurodevelopmental impairment.
Prevalence of cocaine use among residents of New York City who committed suicide during a one-year period
Authors: P M Marzuk, K Tardiff, A C Leon, M Stajic, E B Morgan, J J Mann
Journal: American Journal of Psychiatry (1992)

In the mid-1980s the form of cocaine called "crack" became widely available in New York City. The authors sought to determine the prevalence of cocaine metabolites detected at autopsy in persons who committed suicide in New York City during this period.Individual reviews of the autopsy and toxicological records of all persons under the age of 61 who had committed suicide in the city during a 1-year period were conducted to determine demographic characteristics, suicide methods, and cocaine and alcohol use at the time of death.In one of every five cases studied, the person who committed suicide had used cocaine within days of his or her death. The prevalence of cocaine use among young Hispanic males who committed suicide was 45%. Persons who were young, black, or Hispanic and who had used alcohol immediately before the fatal injury were most likely to have been recent cocaine users. After controlling for demographic variables and ethanol use, the investigators found that individuals who committed suicide with firearms were twice as likely to have used cocaine as those who used other methods.In contrast to the results of regional and household surveys during this period, which suggested that the current prevalence of cocaine use in New York City was 3%-5%, these results suggest a high prevalence of cocaine use in the days immediately preceding death by young persons who commit suicide. Additional studies are needed to determine how cocaine may act as a risk factor for suicide.