tbuckley/cabot-search huggingface dataset:
Abstract 15184: In vivo Functional cDNA Selection Identifies Ghrelin as a Novel, Powerful Cardioprotective Molecule
Authors: Giulia Ruozi, Serena Zacchigna, Antero Macedo, Matteo Dalferro, Alberto Clicerio, Antonella Falcione, Miguel Mano, Lorena Zentilin, Gianfranco Sinagra, Mauro Giacca
Journal: Circulation (2010)

Introduction:  To identify novel cardioprotective genes we developed an innovative functional selection approach, based on in vivo gene transfer of cDNA libraries using AAV vectors.   Hypothesis:  To support the feasibility of in vivo functional screening, we used a pool of AAV expressing 50 different hormones and growth factors and assessed the hypothesis that the clones enriched by selective pressure effectively promoted cardiac function.   Methods:  After cardiac injection (n=50) of the AAV pool, animals were subjected to myocardial infarction. After 15 days, persisting vector DNA was recovered, recloned into AAV and used for subsequent cycles of functional selection. Individual AAV vectors expressing the selected clones were eventually tested for cardioprotective activity in vitro on primary cardiomyocytes and in mouse models of cardiac fibrosis (isoproterenol i.p. 200 mg/Kg) or myocardial infarction by echocardiography, morphometric and molecular analysis (n=10 per group).   Results:  In vivo functional selection led to marked enrichment for surviving cardiomyocytes expressing Ghrelin, a neuro-hormone secreted upon starvation. In vitro, transduction with AAV-Ghrelin resulted in improved survival of cardiomyocytes after isoproterenol (>90% vs 60% vs    Conclusions:  In conclusion, these results support the feasibility of our innovative in vivo selection approach and identify Ghrelin as a novel and powerful molecule protecting from cardiac apoptosis and providing benefit upon cardiac damage.
Abstract 12545: Potential Role of MicroRNA-29b in Atrial Fibrillation-Promoting Fibrotic Remodeling
Authors: Kristin Dawson, Reza Wakili, Balazs Ordog, Sebastian Clauss, Xiao Yan Qi, Sophie Cardin, Stefan Kaab, Stanley Nattel
Journal: Circulation (2010)

Introduction:  Heart failure (HF) causes an atrial fibrotic substrate for atrial fibrillation (AF) maintenance, but the underlying mechanisms are incompletely understood. MicroRNA (miR) 29b suppresses collagen production and decreased miR29b expression promotes fibrotic responses. This study assessed the potential contribution of miR29b changes to HF-induced atrial fibrotic remodeling.   Methods:  Experiments were performed in a canine HF model of AF and atrial fibrosis induced by ventricular tachypacing (VTP, 240 bpm). We studied 4 groups: 24 h, 1 wk, 2 wk VTP and control (CTL) dogs (n=8/group). Expression of miR29b in left atrial (LA) tissue and of extracellular matrix (ECM) target genes collagen (COL) 1A1, COL3A1 and fibrillin (FIB) in isolated LA fibroblasts (AFBs) was assessed by real time qPCR.   Results:  After 1 wk, VTP remodeled atria showed increased AF duration (17-fold***, p   Conclusions:  VTP-induced HF causes a rapid and sustained decrease in miR29b expression, which is followed by increased expression of fibrosis-related miR29b-target ECM genes. TGFβ induces miR29b downregulation in AFBs. In vitro knockdown of miR29b mimics in vivo changes, suggesting a causal role of mir29b downregulation in CHF-related generation of atrial fibrosis via TGFβ signaling.
循证处方：是目标，但开处方者仍需要接受教育并有一定的经验和常识
Authors: Simon, Maxwell, 崔太根（译）, 王海燕（校）
Journal: BMJ (2006)

循证医学被定义为“在充分、清楚和明智地利用现有最好的证据基础上对个体病人的处理作出决定”。在临床实践中受循证医学影响最直接的莫过于用药。就在不久前医生在开处方时还不会担心其用药的选择是否有悖于文献中证据。但现在，医生们越来越多地希望倚助于循证医学证据来支持其用药的决定。。对循证处方的热情是一件好事情，它可以使药物的使用更安全、有效，但同时也造成了一些实际问题。
Abstract 1957: The Carboxyterminal Telopeptide of Procollagen type I and Procollagen type III Aminoterminal Peptide (PIIINP) are Strong Predictors of Cardiovascular Morbidity and Mortality in the Elderly; The Cardiovascular Health Study
Authors: Eddy Barasch, John S Gottdiener
Journal: Circulation (2007)

Background: The fibrillar myocardial extracellular matrix is mainly composed of type I and III fibrillar collagen and their turnover are reflected in the serum level of carboxyl-terminal propeptide type I (PIP) and procollagen type III aminoterminal peptide (PIIINP). The prognostic value of these biomarkers in elderly individuals with heart failure (HF) or other cardiovascular disease (CVD) and in healthy subjects is largely unknown. Aim: To determine the predictive value of PIP, its degradation metabolite, carboxyterminal telopeptide of procollagen type I (CTIP), and PIIINP serum level for the incident CV morbidity and mortality in a nested case control study of community-dwelling elderly individuals enrolled in the Cardiovascular Health Study (CHS). Methods: In 880 participants (ppts) enrolled in the CHS (mean age 77 ± 6 yrs, 52 % males, 79 % white), 310 with HF, 287 controls (no HF but other CVD) and 283 healthy ppts, serum levels of PIIINP, PIP and CTIP were measured by radioimmunoassay. The number of incident CV disease and death were recorded. Wilcoxon rank sum test, Kruskal-Wallis test, and Cox proportional hazards regression were used as appropriate. Results: Age, gender and race and fully adjusted analyses are presented in the table : Conclusions: In this large elderly cohort, there is a strong association between CTIP, PIIINP and incident CVD and death. Elevated CTIP level increases the risk of death more than 50% and of symptomatic PVD by almost two-fold. Whereas PIIINP has a lower predictive power than CTIP, PIP was not associated with incident CVD or death. Serum CTIP and PIIINP have a good prognostic value for both incident CVD and death in elderly individuals with or without known CV disease.
Abstract 16418: Standardized STEMI Alert Protocols and Interfacility Transfer Guidelines Optimize STEMI Reperfusion Times
Authors: David R Burt, Chris Ghaemmaghami, Robert Rosen, Larry Gimple, Robert O'Connor
Journal: Circulation (2011)

Introduction: Current AHA STEMI guidelines indicate a door to PCI time of 90 minutes and a door to fibrinolysis time of 30 minutes. These intervals have significant implications for hospitals that ...
Abstract P168: Determinants of Smoking and Quitting in an HIV Cohort Using a Validated Natural Language Processing Tool
Authors: Susan Regan, James B Meigs, Steven K Grinspoon, Virginia A Triant
Journal: Circulation (2012)

Background: Tobacco smoking is widespread among HIV patients and is likely to contribute to the development of chronic diseases, yet accurate information on smoking is often difficult to obtain from observational data sources. We sought to validate a natural language processing (NLP) classifier to identify smokers among HIV and control cohorts and investigate whether HIV is an independent predictor of smoking and failure to quit smoking. Methods: We applied an NLP classifier developed within the Partners HealthCare System to electronic medical records for a cohort of HIV patients and a control cohort matched on age, gender, race, and number of clinical encounters. The NLP classifier searches free text notes for “tokens”, phrases containing smoking-related words, and assigns a smoking status (current, former, or non-smoker) to each token. We developed an algorithm for combining token classifications from a 12 month period into a single smoking status (current vs. non-smoker). We validated the yearly smoking status on a random sample of 500 patients (250 from each cohort) using as a gold standard a trained nurse medical record reviewer who assigned a tobacco smoking status to each patient for each calendar year observed. We calculated sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Using NLP, we classified the full cohorts as ever versus never smokers and current versus non-smokers at last observation. We used logistic regression to assess HIV as a predictor of smoking and failure to quit (current smoking among ever smokers). Results: Smoking-related tokens were found in the records of 2926/3554 HIV and 7039/9601 non-HIV patients, providing 34,956 patient years of data. Using NLP to assign smoking status by year yielded sensitivity of 92.4, specificity of 86.2, and AUC of 0.89 (95% confidence interval [CI] 0.88-0.91). NLP assignment of ever versus never smoking status yielded sensitivity of 94.3, specificity of 73.4 and AUC of 0.84 (95% CI 0.81-0.87). Performance of the classifier did not vary by HIV status, gender, age, calendar year, or number of tokens/year. Ever and current smoking were more common in HIV patients than controls (54% vs. 44% and 42% vs. 30%, respectively, both p&lt;0.001). In multivariate models adjusting for demographics, cardiovascular risk factors, coronary heart disease and history of psychiatric illness, HIV was an independent predictor of ever smoking (odds ratio [OR] 1.41, 95% CI 1.29-1.54, P &lt;0.001), current smoking (OR 1.57, 95% CI 1.43-1.72, P&lt;0.001), and failure to quit (OR 1.51, 95% CI 1.31-1.75, P&lt;0.001). Conclusions: We validated a novel tool to ascertain smoking status from HIV observational cohort data. HIV was independently associated with both smoking and failure to quit smoking. These data underscore the need for aggressive smoking cessation strategies specific to HIV patients.
NATURE AND QUANTITATIVE DETERMINATION OF THE REDUCING SUBSTANCE IN NORMAL AND PATHOLOGIC CEREBROSPINAL FLUID
Authors: Oscar M. Schloss, Louis C. Schroeder
Journal: JAMA Pediatrics (1916)

I. INTRODUCTION  During the past year we have had opportunity to make a series of quantitative determinations of the reducing power of various specimens of normal and pathologic cerebrospinal fluid, and also to carry out certain observations concerning the nature of the reducing substance. The data thus derived serve as the basis of this communication.  II. THE NATURE OF THE REDUCING SUBSTANCE  It is generally assumed that the reducing agent in cerebrospinal fluid is dextrose—the sugar of blood and body fluids. A review of the literature, however, discloses that there has been considerable divergence of opinion. Halliburton, 1 whose views are quoted in several current textbooks, concluded that the reducing substance was pyrocatechin or a pyrocatechin derivative. Connall 2 states that it is galactose, although he gives no references or experimental data to uphold this view. The observations of Nawratski, 3 Zdarek, 4 Rossi 5 and others, however, indicate that
Abstract 12964: Over Expression of miR1 Leads to EAD Development in Cardiomyocytes by Increasing CaMKII and Calcium Current
Authors: Guoliang Ding, Hua Cheng, Tao Chen, Brian H Crawford, Talib B Saafir, Mary B Wagner
Journal: Circulation (2011)

Introduction:  miR1 has been shown to induce cardiac arrhythmias in animal models but the mechanism is unclear. We overexpress miR1in rat cardiomyocytes and investigated the cellular mechanism of arrhythmia development.   Methods:  Rat cultured ventricular cardiomyocytes were infected with adenovirus-miR1 and adenovirus-GFP (control). Voltage and current clamp were used to record calcium current and action potentials at 35°C. Cells were loaded with Fura2-AM for measurement of calcium transients.   Results:  Action potential duration at 90% repolarization (APD 90 ) was 542.4% longer in ad-miR1 cardiomyocytes compared to control (377.1±137.2 ms vs. 58.7±7.2 ms vs., n=7, p 90  was due, in part, to a 174% increase in the incidence of early afterdepolarizations (EADs) in ad-miR1 cardiomyocytes (22±2 EADs/100 beats vs. 8±1 EADs/100 beats, n=25, P 2+ /calmodulin-dependent protein kinase II (CamKII) activation, we blocked CamKII with KN93 (1μ M) in ad-miR1 cardiomyocytes. Calcium current decreased from 18.7±0.7 pA/pF to 10.0±1.0 pA/pF, (n=11, p 90  (377.1±137.2 ms to 73.4±13.7 ms, n=11, p 90  decreased in ad-miR1 cells, but remained longer than in control cells (67.3±1.7 ms vs 18.8±1.6 ms, n=16 and 13,  p  90  and that other currents may also involved in this prolongation in ad-miR1 infected cardiomyocytes.   Conclusions:  Overexpression of miR1 induced EADs in rat cardiomyocytes, in part, by increasing calcium current and CaMKII, which may be a mechanism of arrhythmias by miR1 overexpression in animal models.
Estrogens down-regulates cyclin-dependent kinase inhibitors and controls cell cycle progression in human uterine leiomyoma
Authors: Chi-Heum Cho, Soon-Do Cha, Sang-Hoon Kwon, Sabarish Ramachandran
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1545 

Objective : Regulation of cyclin dependent kinase (CDK) inhibitor expression, and particularly that of p21 Waf1/Cp1 and p27 Kip1 , has emerged as a critical aspect of growth control in normal mammalian cells and as a frequent point of dysregulation in a wide variety of tumors. Estrogens are essential for normal development and function of female reproductive tissues, yet play a pivotal, causative role in the initiation and progression of cancer. Our objective was to evaluate whether 17β-estradiol exerts any growth regulatory actions in normal and human uterine leiomyoma tissue through regulation of events in the G1 phase of the cell cycle. Material and Methods : The p21 and p27 protein and mRNA expression levels both in tissues and cultured uterine leiomyoma cells were determined by immunohistochemical staining, Western blot and real time PCR analysis. Role of 17β-estradiol on uterine leiomyoma was monitored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blot analysis. Results : We detected that p21 and p27 protein and messenger RNA expressions were down regulated in uterine leiomyoma tissue and cultured cells compared to normal myometrium. 17β-estradiol at 10 nM concentration elicited inhibition of Kip protein expression by regulating the expression of Cdk2 as a result cells manifested greater proliferation and viability. Conclusions : Our results suggest a new paradigm that estrogen-induced down regulation of the CDK inhibitors in leiomyoma controls the early stage of cell cycle progression. This study provides better understanding of the control exerted by estrogen over CDK inhibitors and its interaction with cyclins and CDK2/4 complexes which ultimately regulate human uterine leiomyoma formation and disease progression.
Abstract 535: Steepening Left Ventricle to Aortic Root Angle is Associated With Increasing Age and Basal Septal Thickness: Implications for Percutaneous Aortic Valve Replacement
Authors: Deborah H Kwon, Paul Schoenhagen, Samir Kapadia, Ronan J Curtin, Scott D Flamm, Lars G Svensson, E Murat Tuzcu, Milind Y Desai
Journal: Circulation (2009)
Defining two prognostic groups of metastatic gastric cancer: FLOT3 trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
Authors: S. Al-Batran, R. Hofheinz, N. Homann, G. Illerhaus, U. M. Martens, J. Stoehlmacher-Williams, H. Schmalenberg, K. B. Luley, N. Prasnikar, M. Egger, S. Probst, J. T. Hartmann, M. H. Moehler, D. Arnold, W. Fischbach, C. Pauligk, S. P. Moenig, P. Piso, E. Jaeger
Journal: Journal of Clinical Oncology (2011)

4070 Background: A prognostic model for metastatic gastric cancer has not been established yet. Methods: Pts with untreated gastric cancer were prospectively stratified into 3 groups: operable (OD), limited metastatic (LD), or extensive metastatic (ED) disease using a predefined algorithm and treated with 5-FU, oxaliplatin, leucovorin and docetaxel (FLOT). LD was defined as having all of the following: distant intra-abdominal lymph node metastases and/or a maximum of 1 organ involved in metastatic disease (distant extra-abdominal lymph node metastases were considered as 1 organ), normal serum alkaline phosphatase, < 5 liver lesions, no clinically apparent peritoneal carcinomatosis, no lymphangiosis carcinomatosa of the lung or malignant pleural effusion, and ECOG ≤ 1. All other metastatic pts were ED. Pts with OD received 4 preoperative cycles of FLOT and were operated (D2-resection) followed by 4 postoperative cycles. Pts with LD received 8 cycles with surgery allowed for complete macroscopic resection. Pts with ED received 8 cycles with surgery allowed for palliation only. The study had 80% power to detect a HR of 0.55 for overall survival in favor of the LD group (vs. ED group; 2-sided log-rank p=0.05). Results: A total of 252 pts (OD/LD/ED: 52/68/132) were included between Feb 2009 and Jan 2010 in 47 centers, of whom 239 pts were eligible. All 3 groups received a median of 8 cycles of FLOT. The primary endpoint of the study was met: median OS was 18.6 vs. 10.9 months in pts with LD vs. ED, respectively (HR 0.4; 95% CI, 0.28 – 0.63; p <0.001). Median OS in the OD group (not reached) was superior to LD and ED groups. There were also significant differences in the distribution of PFS according to group (p<0.001 for all comparisons). Surgical or local ablative treatment was conducted in 95.7%, 42.64%, and 5.4% in the OD, LD, and ED groups, respectively (p<0.001 for all comparisons). Grade 3/4 toxicities were similar among groups (70.6%, 72.1%, and 80.9%, respectively), but anemia, pain, and infection were significantly more frequent in ED pts. Conclusions: This simple clinical score was able to stratify pts with metastatic gastric cancer into different clinically relevant prognostic groups.
Abstract 13441: Two Forms of Autophagy in the Heart - Constitutive Autophagy via an LC3-dependent Pathway and Starvation-Induced Autophagy via a Rab9-Dependent Pathway
Authors: Yoshiya Monden, Yasuhiro Maejima, Masaaki Komatsu, Mondira Kundu, Junichi Sadoshima
Journal: Circulation (2011)
Abstract 9612: Does quantification of Epicardial Adipose Tissue (EATv) and Intrathoracic Fat (ITFv) Volume with Noncontrast Cardiac Computed Tomography (CCT) improve Coronary Events (CE) Prediction Over Clinical Information and Coronary Artery Calcium Score (CACS)?
Authors: Farshad Forouzandeh, Su Min Chang, Kamil Muhyieddeen, Rasheed R Zaid, Alejandro R Trevino, Jiaqiong Xu, Faisal Nabi, John J Mahmarian
Journal: Circulation (2011)

Background: CCT allows for calculation of CACS and measurement of EATv and ITFv. It is unclear whether EATv and ITFv provide additional value over CACS and clinical information in predicting CE. Methods: 760 consecutive symptomatic patients without known coronary disease underwent CCT and were followed up to 5 years (median 3.3 years) for CE (cardiac death, non fatal MI, and acute coronary syndrome with &gt;70% coronary artery stenosis). The mean age was 54.4 ±13.7 years, 60 % were female, 15% were diabetics, mean body mass index (BMI) of 30.6 kg/m 2 and mean Framingham risk score (FRS) of 8.2. The ITFv and EATv were calculated with semiautomated method. Fat tissue were automatically recognized by threshold between -40 and-200 HU. Results: Compared to 715 event-free patients, the 45 patients who had CE were older (64.8 vs 53.7 y/o p&lt;0.001), more male (60% vs 40% p=0.008), higher mean FRS (14.3 vs 7.8 p&lt;0.001) and higher median CACS (268 vs 0 p &lt;0.001). They also had higher median EATv (154 vs.116 ml, p = 0.006) and ITFv (330 vs 223 ml, p = 0.001), higher prevalence of EATv &gt;125 ml (67% vs. 44%, p = 0.005)and ITFv&gt;250 ml (64% vs. 42%, p = 0.003). Both EATv and ITFv were predictors of CE and remained so after adjustment for FRS, BMI and CACS &gt;400 (Table 1). The area under the curve from ROC analyses showed trends to improve CE prediction when fat volume was added to FRS, BMI and log (CACS±1) (0.839 for EATv&gt;125ml, 0.843 for ITFv&gt;250ml vs. 0.828, p=0.14 and 0.11 respectively). On the other hand, CACS significantly improved the prediction when added to FRS and BMI (0.828 vs 0.724 p=0.001) Conclusions: Symptomatic patients with CE had larger ITFv and EATv and higher CACS. Although both EATv and ITFv provided some incremental value over clinical information, CACS remained the strongest predictor of outcome
Abstract 16232: Prognostic Significance of Hyponatremia among Ambulatory Heart Failure Patients with Preserved Ejection Fraction
Authors: Chirag Bavishi, Sameer Ather, Arvind Bambhroliya, Biykem Bozkurt, Kumudha Ramasubbu, David Aguilar, Anita Deswal
Journal: Circulation (2012)

Background: Hyponatremia is an established predictor of adverse outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF). However, the prevalence and prognostic significan...
Abstract 17607: Substrate Based Atrial Fibrillation Ablation Guided by Voltage Gradient Mapping: Initial Results and Near-Term Clinical Outcome
Authors: Steven Bailin, Craig Hoffman, Robert West
Journal: Circulation (2011)

Background: Ablation of atrial fibrillation (AF) is anatomic based with isolation of pulmonary veins (PVs), generally in combination with linear ablation. Because AF is chaotic, activation mapping cannot reveal underlying mechanisms or reasons for success or failure. We report substrate based ablation guided by voltage gradient mapping (VGM) provides promising initial and near-term success. Methods and Results: 55 consecutive patients undergoing AF ablation, 29 paroxysmal (PAF) and 26 chronic (CAF), had contact voltage mapping within the left and right atrium, PVs, SVC, and IVC. Adjustment of voltage levels displayed low voltage connections between higher voltage regions. Ablation of low voltage bridges (LVB) was performed until repeat maps had no demonstrable LVB. Ablation endpoints were termination of AF and failure to induce AF or tachycardia. Clinical success was defined by the absence of recurrent AF (primary endpoint), and freedom from sustained arrhythmias (secondary endpoint) documented by 30 day monitoring 4 months following ablation. LVB ablation resulted in AF termination in 43/46 patients (93%) and AF was not inducible in 52/55 (95%). Single procedure success for prevention of recurrent AF was 51/55 (93%) and freedom from atrial arrhythmia was 39/55 (71%) (PAF: 86%; CAF: 56%). Following a second procedure the arrhythmia free success was 49/55 (89%); PAF: 97%; CAF: 81%. Conclusions: We conclude that VGM of atrial substrate is an effective tool to guide ablation therapy. This method provides a high single procedure success in both PAF and CAF achieving the primary endpoint in 95% and secondary endpoint of 71%.
Body Fat Distribution and Risk of Incident and Regressed Nonalcoholic Fatty Liver Disease
Authors: Donghee Kim, Goh Eun Chung, Min-Sun Kwak, Hyo Bin Seo, Jin Hwa Kang, Won Kim, Yoon Jun Kim, Jung-Hwan Yoon, Hyo-suk Lee, Chung Yong Kim
Journal: Clinical Gastroenterology and Hepatology (2015)
Abstract 2890: The Long Term Outcome Of Treated Presensitized Patients Who Undergo Heart Transplantation: Is It Successful?
Authors: Jon Kobashigawa, Jignesh Patel, Matt Kawano, Grace Wu, Michelle Kittleson, Krista Kiyosaki, Jamie Moriguchi, Abbas Ardehali
Journal: Circulation (2007)

Background: Sensitized patients prior to heart transplantation are reportedly at risk for hyperacute rejection and for poor outcome after heart transplantation. It is not known whether reduction of circulating antibodies pre-transplant alters post-transplant outcome. Methods: Between July 1993 and July 2003 we reviewed 523 heart transplant patients of which 95 had pre-transplant PRAs &gt;10%. 21/95 were treated pre-transplant for circulating antibodies. These 21 patients had PRAs greater than 10% (majority 50%–100%) and were treated with combination therapy including plasmapheresis and intravenous gamma globulin to reduce antibody counts. The 74 untreated patients with PRAs &gt;10% (untreated presensitized group) and those patients with PRAs &lt;10% (control group) were used for comparison. Routine post-transplant immunosuppression included triple drug therapy (tacrolimus, mycophenolate, and corticosteroids). Results: Circulating antibody levels pre-transplant decreased from a median of 77.5 to 29.0% (p = 0.017), which allowed a negative prospective donor specific cross match and successful heart transplantation. Compared to the untreated presensitized group, and the control group, the treated sensitized patients had similar five year survival (81.1% vs. 75.7% vs. 71.4%, p=0.523) and freedom from cardiac allograft vasculopathy (74.3% vs. 72.7% vs. 76.2%, p=0.850). Conclusion: Treatment of sensitized patients pre-transplant appears to result in comparable long term outcome after heart transplant.