tbuckley/cabot-search huggingface dataset:
Abstract P362: Association of DNA Methylation Age With Risk of Type 2 diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Nicholas S Roetker, James S Pankow, Heather H Nelson, Weihua Guan, Chindo Hicks, Thomas Mosley
Journal: Circulation (2015)

Introduction: It has been proposed that DNA methylation patterns can be used to characterize rate of aging, but it is not known whether methylation age associates with aging-related diseases and conditions independently of chronological age and other risk factors. Hypothesis: There is a positive association between age acceleration (defined as the difference between DNA methylation age and chronological age) and risk of type 2 diabetes (T2D). Methods: We estimated DNA methylation age in African American men and women of the Atherosclerosis Risk in Communities Study using two published predictors. Incident T2D was identified from follow-up visits and telephone interviews. Logistic and Cox proportional hazards regression models were used to estimate the association of age acceleration with incident T2D, modeling age acceleration both continuously and categorically in three percentile groups (0-25th, 25-75th, 75-100th). Regression models were adjusted for chronological age, sex, white blood cell distribution, education, smoking, alcohol, sport index, body mass index, waist to hip ratio, blood pressure, antihypertensive and lipid-lowering medication, HDL and LDL cholesterol, and triglycerides. Results: After adjustment for chronological age, sex, and white blood cell type proportions, those with greater age acceleration were more likely to have prevalent T2D (p-trend ≤ 0.003 across percentile categories of age acceleration for both DNA methylation predictors). Among 1,547 participants who were free of T2D at baseline (mean age: 56 years, range: 47-70), there were 170 incident cases of T2D over a mean 5.4 years of follow-up. T2D incidence was not associated with age acceleration in either crude or risk factor-adjusted models. In the fully-adjusted logistic regression models, odds ratios (95% confidence intervals) for T2D across the percentile categories of age acceleration were 1 (ref.), 0.92 (0.58, 1.45), and 1.42 (0.84, 2.40); and 1 (ref.), 0.87 (0.55, 1.39), and 0.93 (0.52, 1.64), respectively, for the two DNA methylation age predictors. Conclusion: In conclusion, DNA methylation age acceleration, proposed as a marker of the rate of aging, was associated cross-sectionally with prevalent diabetes, but did not predict risk of T2D independently of chronological age. Additional prospective studies are needed to explore relationships with development of other chronic conditions in order to determine if DNA methylation age can serve as a useful proxy for rate of aging.
Abstract 12364: Hyperintense Coronary Plaque with Non-Contrast T1-Weighted Magnetic Resonance Imaging Indicates Positive Remodeling, Remarkable Low CT Density, and High Incidence of Spotty Calcification
Authors: Teruo Noguchi, Tomohiro Kawasaki, Atsushi Tanaka, Yoichi Goto, Nobuhiko Koga
Journal: Circulation (2011)

Background: Our prior study has demonstrated that the presence of a coronary hyperintense plaque (HIP) on non-contrast T1-weighted (T1W) magnetic resonance imaging is associated with positive coron...
HIV and Psychoimmunology: Evidence Promising and Forthcoming
Authors: David Miller, Kenneth H Nott, Kavita Vedhara
Journal: Journal of the Royal Society of Medicine (1994)

Promising evidence on the validity ofwhat came to be called 'psychoimmunology' (PI) has been recorded since the time of Galen, who reputedly observed that women of a melancholic temperament were more prone to develop cancer than those of a sanguine nature2. Forthcoming evidence, on the other hand, has fallen far short of the ideal. Conclusive evidence of clear links between disease, immunity and psychological factors is very rare. Despite this, new findings are looked upon with an interest and enthusiasm that even the most circumspect of observers finds hard to disguise. A relatively recent editorial in The Lancet3, which reviewed evidence for, and questioned the clinical importance of, a link between emotion and immunity, concluded:
Abstract 17963: Cardioprotective Effects of Ecklonia Cava Polyphenol on Doxorubicin-induced Cardiomyopathy in Rats
Authors: Hyo-Suk Ahn, Hui-Kyung Jeon, Ki Tae Kim, Ho-Joong Youn
Journal: Circulation (2014)

Introduction: Long-term therapy with doxorubicin is associated with a high incidence of a cumulative and irreversible dilated cardiomyopathy, despite of its broad anti-neoplastic effectiveness. The goal of this study was to evaluate the cardioprotective effects and safety of seapolyphenol (polyphenol purified from Ecklonia cava) against doxorubicin-induced cardiotoxicity in an animal rat model. Methods and Results: In total 28 rats including doxorubicin and control groups, baseline and 6 weeks follow up echocardiography were practiced. Left ventricular ejection fraction significantly decreased and the left ventricular end diastolic/systolic dimension and LV mass index significantly increased in single doxorubicin group compared to high dose seapolynol plus doxorubicin group. Also, electron microscopic finding showed less impaired myofiber and mitochondria in high dose seapolynol plus doxorubicin group than in single doxorubicin group. Conclusions: Our data showed that high dose seapolynol had cardioprotective effects against doxorubicin-induced cardiotoxicity in an animal rat model with the evidence of electron microscopic finding in addition to echocardiographic results..
Abstract 4827: Role of Left Ventricular Dyssynchrony in Functional Mitral Regurgitation in Patients with Dilated Cardiomyopathy: A Comparison Study with Geometric Parameters of Mitral Apparatus Estimated with 3d Echocardiography
Authors: Woonggil Choi, Soohyun Kim, Seongill Woo, Deahyuk Kim, Keumsoo Park, Woohyung Lee, June Kwan
Journal: Circulation (2008)

Objective: Functional mitral regurgitation (FMR) occurs commonly in patients with dilated cardiomyopathy (DCM). The aim of this study was to compare the roles of Left Ventricle(LV) dyssynchrony and geometric parameters of mitral apparatus as determinants of FMR in patients with DCM. Methods: Fourteen DCM patients without FMR and 15 DCM patients with FMR (ERO = 0.11 ± 0.029 cm 2 ) were enrolled. Effective regurgitant orifice (ERO) area and tissue Doppler-derived dyssynchrony index (DI: the standard deviation of time to peak myocardial systolic contraction of eight segments) were measured. The estimated DIs were corrected by the cycle length (CL) of each patient (cDI (%) = DI/CL*100). Using real-time 3D echocardiogrphy, mitral tenting area (MVT) and the degrees of displacement of anterior (APMD) and posterior (PPMD) papillary muscles were estimated. All geometric measurements were corrected (c) by the height of each patient. Results: There was no significant (p &gt; 0.05) difference in LV Ejection Fraction and cLVEDV between two patient groups. cDI, cMVT, cAPMD and cPPMD significantly (p &lt; 0.05) increased in the patient with FMR comparing with those in patients without FMR. cDI (r = 0.42), cMVT (r = 0.74), cAPMD (r = 0.63) and cPPMD (r = 0.64) showed significant (p &lt; 0.05) correlations with ERO. cMVT was found to the strongest independent predictor of ERO with multivariate regression analysis, whereas cDI did not enter into the model. Conclusions: The degree of MV tenting rather than LV dyssynchrony was found to be the main determinant of FMR in DCM. However LV dyssynchrony also has a minor independent association with FMR.
Percutaneous Mitral Valve Edge-to-Edge Repair
Authors: Georg Nickenig, Rodrigo Estevez-Loureiro, Olaf Franzen, Corrado Tamburino, Marc Vanderheyden, Thomas F. Lüscher, Neil Moat, Susanna Price, Gianni Dall’Ara, Reidar Winter, Roberto Corti, Carmelo Grasso, Thomas M. Snow, Raban Jeger, Stefan Blankenberg, Magnus Settergren, Klaus Tiroch, Jan Balzer, Anna Sonia Petronio, Heinz-Joachim Büttner, Federica Ettori, Horst Sievert, Maria Giovanna Fiorino, Marc Claeys, Gian Paolo Ussia, Helmut Baumgartner, Salvatore Scandura, Farqad Alamgir, Freidoon Keshavarzi, Antonio Colombo, Francesco Maisano, Henning Ebelt, Patrizia Aruta, Edith Lubos, Björn Plicht, Robert Schueler, Michele Pighi, Carlo Di Mario
Journal: Journal of the American College of Cardiology (2014)
Fas/Fas ligand-mediated elimination of antigen-bearing Langerhans cells in draining lymph nodes
Authors: None Kawamura, None Azuma, None Kayagaki, None Shimada, None Yagita, None Okumura
Journal: British Journal of Dermatology (1999)

Epidermal Langerhans cells (LC) are potent antigen-presenting cells (APC) that play a crucial part in initiating cutaneous immune responses. Although functional roles of LC as APC in the draining lymph node have been well investigated, little is known about the fate of LC after the antigen presentation to T cells. In this report, we demonstrate that antigen-bearing LC that migrated into the draining lymph nodes and were identified as fluorescent cells after skin painting with fluorescein isothiocyanate also expressed the Fas antigen. Clearance of the antigen-bearing LC was significantly delayed and the ratio of dead cells was reduced in Fas-deficient lpr and Fas ligand (FasL)-deficient gld mice at 2 days after skin painting, suggesting the involvement of a Fas/FasL-mediated pathway in the elimination of antigen-bearing LC in draining lymph nodes. These results suggest that a substantial population of LC after antigen presentation may undergo Fas/FasL-mediated apoptosis and that the elimination of active APC may be important for preventing excess immune responses.
Arterial Thrombotic Complications Are Uncommon in Patients without Cardiovascular Risk Factors and Occur at Equivalent Rates in Chronic Myeloid Leukemia (CML) Patients Treated with Imatinib and Nilotinib
Authors: Hesam Hekmatjou, Gail J. Roboz, Ellen K. Ritchie, Sangmin Lee, Pinkal Desai, Joseph M. Scandura, Sandra Allen-Bard, Paul Christos, Richard T. Silver, Eric J. Feldman
Journal: Blood (2014)
Pachyonychia congenita patients with mutations in KRT6A have more extensive disease compared with patients who have mutations in KRT16
Authors: K.M. Spaunhurst, A.M. Hogendorf, F.J.D. Smith, B. Lingala, M.E. Schwartz, A. Cywinska-Bernas, K.J. Zeman, J.Y. Tang
Journal: British Journal of Dermatology (2011)

Pachyonychia congenita (PC) is an autosomal dominant, very rare keratin disorder caused by mutations in any of at least four genes (KRT6A, KRT6B, KRT16 or KRT17), which can lead to hypertrophic nail dystrophy and palmoplantar keratoderma, among other manifestations. Classically, patients with mutations in KRT6A and KRT16 have been grouped to the PC-1 subtype (Jadassohn-Lewandowsky type) and KRT6B and KRT17 to PC-2 (Jackson-Lawler type).To describe clinical heterogeneity among patients with PC who have genetic mutations in KRT6A and KRT16.In 2004, the Pachyonychia Congenita Project established the International PC Research Registry (IPCRR) for patients with PC. All patients reporting here underwent genetic testing and responded to a standardized, validated survey about their PC symptoms. We report results from 89 patients with KRT6A mutations and 68 patients with KRT16 mutations.Patients with PC who have KRT6A and KRT16 mutations display distinct phenotypic differences. Patients with PC-K6a experience earlier onset, more extensive nail disease and more substantial disease outside palms and soles, as they reported a higher prevalence of oral leucokeratosis (P < 0·001), cysts (P < 0·001) and follicular hyperkeratosis (P < 0·001) compared with their PC-K16 counterparts.Phenotypic differences between patients with KRT6A and KRT16 mutations support adoption of a new classification system based on the mutant gene (PC-6a, PC-16) rather than the PC-1 nomenclature.
Prediction of adverse events during intensive induction chemotherapy for acute myeloid leukemia or high‐grade myelodysplastic syndromes
Authors: Sarah A. Buckley, Megan Othus, Vladimir Vainstein, Janis L. Abkowitz, Elihu H. Estey, Roland B. Walter
Journal: American Journal of Hematology (2014)

Intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with significant treatment‐related morbidity and mortality. Herein, we investigate how pretreatment characteristics relate to early adverse outcomes in such patients, studying 205 consecutive individuals receiving curative‐intent induction chemotherapy with cytarabine and an anthracycline (“7 + 3”; n = 175) or a “7 + 3”‐like regimen ( n = 30). Among the entire cohort, baseline grade 4 neutropenia (i.e., absolute neutrophil count &lt;500 cells/µL) was associated with development of fever ( P = 0.04), documented infection ( P &lt; 0.0001), and bacteremia ( P = 0.002) but not requirement for intensive care unit‐level care; after exclusion of the 30 patients who received “7 + 3”‐like induction, baseline grade 4 neutropenia remained associated with documented infection ( P &lt; 0.0001) and bacteremia ( P = 0.0005). Among patients achieving a complete remission with the initial treatment cycle, grade 4 neutropenia was associated with delayed neutrophil count recovery ( P &lt; 0.0001). Low monocyte and lymphocyte counts at baseline were similarly associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, cytogenetic/molecular risk, and performance status, the risk of fever, documented infection, or bacteremia was 1.87 (95% confidence interval: 1.04–3.34; P =0.04)‐fold, 4.95 (2.20–11.16; P&lt;0.001)‐fold, and 3.14 (0.99–9.98; P =0.05)‐fold higher in patients with initial grade 4 neutropenia. Together, our studies identify severe baseline neutropenia as a risk factor for infection‐associated adverse events after induction chemotherapy and may provide the rationale for the risk‐adapted testing of myeloid growth factor support in this high‐risk AML/MDS patient subset. Am. J. Hematol. 89:423–428, 2014. © 2014 Wiley Periodicals, Inc.
Abstract 3501: EGFR tyrosine kinase inhibitors combined with cytotoxic drugs for treatment of NSCLC with EGFR gene mutations: Efficacy and mechanisms
Authors: Ryohei Yoshida, Synsuke Okumura, Takaaki Sasaki, Yoshinobu Ohsaki
Journal: Cancer Research (2015)

Abstract Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved overall survival in non-small-cell lung cancer (NSCLC) patients whose tumors have EGFR activating mutations. After treatment with EGFR-TKIs, NSCLC tumors with EGFR activating mutations become resistant to EGFR-TKIs, and development of novel treatment strategies is needed to improve survival in such patients.Next-generation EGFR-TKIs have been developed, and a clinical trial showed clinical activity of 3rd generation EGFR-TKIs in patients with acquired resistance, especially secondary mutation T790M to EGFR-TKIs. Moreover, clinical trials demonstrated survival benefit of combination with cytotoxic agents and EGFR-TKIs in patients with EGFR-mutated NSCLC. In contrast, the IMPRESS study showed that continuation of gefitinib in addition to cisplatin and pemetrexed didn't show survival benefit in patients with acquired resistance to gefitinib.Several basic studies reported that efficacy of targeted therapy combined with chemotherapy is schedule dependent. We, therefore, conducted an in vitro study to develop a novel therapeutic strategy for NSCLC with EGFR mutations. Methods: In vitro effects of docetaxel and an EGFR-TKI, gefitinib (AstraZeneca) or AZD9291 (Selleckchem), were examined in five lung cancer cell lines (PC9, PC9GR, HCC827, HCC827GR, and H1975) using a 3D culture model (PrimeSurface 96, SUMITOMO BAKELITE CO.). The NSCLC cells were treated with the combinationeither concurrently or sequentially (EGFR-TKIs after docetaxel or docetaxel after EGFR-TKIs). Combination Index (CI) values were calculated at various levels of cytotoxicity (the Chou-Talalay method). We evaluated changes in MAPK pathway activation and in expressions of Bcl2 family proteins and cleaved PARP (Cell Signaling) by western blot analysis. Results: Docetaxel followed by EGFR-TKIs weremore effective at CI, compared with EGFR-TKIs followed by docetaxel in two of the five cell lines with EGFR activating mutations, PC9GR (EGFR19del+T790M) and HCC827GR (EGFR19del+METamp) cells. The HCC827GR cells were likely to be more sensitive than PC9GR to the combination with docetaxel and gefitinib. The combo led to inactivation of the MAPK pathway and alteration of the Bcl2 family proteins. d) Conclusion: In conclusion, our results suggest that the sequential combination of docetaxel followed by EGFR-TKIs was effective against NSCLC with acquired resistance to EGFR-TKIs. Citation Format: Ryohei Yoshida, Synsuke Okumura, Takaaki Sasaki, Yoshinobu Ohsaki. EGFR tyrosine kinase inhibitors combined with cytotoxic drugs for treatment of NSCLC with EGFR gene mutations: Efficacy and mechanisms. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3501. doi:10.1158/1538-7445.AM2015-3501
The effect of lithium on impulsive aggressive behavior in man
Authors: M H Sheard, J L Marini, C I Bridges, E Wagner
Journal: American Journal of Psychiatry (1976)

The authors conducted a double-blind, placebo-controlled study of the effect of lithium on aggressive behavior. The 66 subjects, who were prisoners in a medium security institution, ranged in age from 16 to 24 years, were physically healthy and nonpsychotic, and had histories of chronic impulsive aggressive behavior. Subjects received lithium or placebo daily for up to 3 months. There was a significant reduction in aggressive behavior in the lithium group as measured by a decrease in infractions involving violence. The authors suggest that lithium can have a clinically useful effect upon impulsive aggressive behavior when this behavior is not associated with psychosis.
Epidemiologic Trends in Neonatal Intensive Care, 2007-2012
Authors: Wade Harrison, David Goodman
Journal: JAMA Pediatrics (2015)

Neonatal intensive care has been highly effective at improving newborn outcomes but is expensive and carries inherent risks. Existing studies of neonatal intensive care have focused on specific subsets of newborns and lack a population-based perspective.To describe admission rates to neonatal intensive care units (NICUs) for US newborns across the entire continuum of birth weight and how these rates have changed across time, as well as describe the characteristics of infants admitted to NICUs.An epidemiologic time-trend analysis was conducted on April 1, 2015, of live births (≥500 g) from January 1, 2007, to December 31, 2012, to residents of 38 US states and the District of Columbia, recorded using the 2003 revision of the US Standard Certificate of Live Birth (N = 17,896,048).Birth year.Crude, stratified (by birth weight), and adjusted admission rates. Trends in birth weight, gestational age, weight for gestational age, and use of assisted ventilation are presented to describe the cohort of admitted newborns.In 2012, there were 43.0 NICU admissions per 1000 normal-birth-weight infants (2500-3999 g), while the admission rate for very low-birth-weight infants (<1500 g) was 844.1 per 1000 live births. Overall, admission rates during the 6-year study period increased from 64.0 to 77.9 per 1000 live births (relative rate, 1.22; 95% CI, 1.21-1.22 [P < .001]). Admission rates increased for all birth weight categories. Trends in relative rates adjusted for maternal and newborn characteristics showed a similar 23% increase (95% CI, 1.22-1.23 [P < .001]). During the study period, newborns admitted to a NICU were larger and less premature, although no consistent trend was seen in weight for gestational age or the use of assisted ventilation.After adjustment for infant and maternal risk factors, US newborns at all birth weights are increasingly likely to be admitted to a NICU, which raises the possibility of overuse of neonatal intensive care in some newborns. Further study is needed into the causes of the increased use observed in our study as well as its implications for payers, policymakers, families, and newborns.
Treatment of Helicobacter pylori infection
Authors: G G. Rao
Journal: BMJ (2000)

Drug use has declined among teenagers in United KingdomEditor-During 1995 a survey of illicit drug use was conducted among teenagers in Europe.The United Kingdom and 22 other countries participated. 1 2British teenagers reported the highest rates of drug use.The survey was repeated in 1999.The population sampled in 1999 consisted of 15 and 16 year old students attending state and private schools in the United Kingdom.Information was elicited from 1280 boys and 1361 girls in 223 schools.A third of girls and 39.5% of boys had used illicit drugs.A total of 36.5% had used cannabis.Glues and solvents had been used by 18.6%, lysergide by 5.2%, amphetamines by 8.9%, and ecstasy (methylenedioxymethamphetamine) by 5.0% (tables 1 and 2).There were several regional variations.Students in Scotland were more likely than others to have used cannabis, any illicit drug, and amphetamines.Respondents in Scotland and Northern Ireland were more likely than others to have used ecstasy and heroin.Those in Northern Ireland reported the greatest use of glues and solvents.Most forms of drug use had declined since 1995.Girls showed significant reductions in their use of cannabis, any illicit drug, solvents, lysergide, amphetamines, "pills" combined with alcohol, ecstasy, and tranquillisers.Among boys the significant falls were in cannabis, any illicit drug, solvents, lysergide, amphetamines, "pills" combined with alcohol, ecstasy, and crack cocaine.The only exception to this trend was heroin, whose use, though still rare, had risen in both sexes.These reductions may be temporary, but they are striking.