tbuckley/cabot-search huggingface dataset:
Integrative Population and Physiological Genomics Reveals Mechanisms of Adaptation in Killifish
Authors: Reid S Brennan, Timothy M Healy, Heather J Bryant, Van La, Patricia M Schulte, Andrew Whitehead
Journal: Molecular Biology and Evolution (2018)

Adaptive divergence between marine and freshwater (FW) environments is important in generating phyletic diversity within fishes, but the genetic basis of this process remains poorly understood. Genome selection scans can identify adaptive loci, but incomplete knowledge of genotype-phenotype connections makes interpreting their significance difficult. In contrast, association mapping (genome-wide association mapping [GWAS], random forest [RF] analyses) links genotype to phenotype, but offer limited insight into the evolutionary forces shaping variation. Here, we combined GWAS, RF, and selection scans to identify loci important in adaptation to FW environments. We utilized FW-native and brackish water (BW)-native populations of Atlantic killifish (Fundulus heteroclitus) as well as a naturally admixed population between the two. We measured morphology and multiple physiological traits that differ between populations and may contribute to osmotic adaptation (salinity tolerance, hypoxia tolerance, metabolic rate, body shape) and used a reduced representation approach for genome-wide genotyping. Our results show patterns of population divergence in physiological capabilities that are consistent with local adaptation. Population genomic scans between BW-native and FW-native populations identified genomic regions evolving by natural selection, whereas association mapping revealed loci that contribute to variation for each trait. There was substantial overlap in the genomic regions putatively under selection and loci associated with phenotypic traits, particularly for salinity tolerance, suggesting that these regions and genes are important for adaptive divergence between BW and FW environments. Together, these data provide insight into the mechanisms that enable diversification of fishes across osmotic boundaries.
Antimicrobial consumption and impact of antimicrobial stewardship programmes in long-term care facilities
Authors: M. Falcone, M. Paul, D. Yahav, G. Orlando, G. Tiseo, V. Prendki, R. Güerri-Fernández, G. Gavazzi, N.T. Mutters, B. Cookson, M. Tinelli Marco
Journal: Clinical Microbiology and Infection (2018)
Abstract 17408: Anatomical Characterization of Mitral Valve Prolapse with Cardiac CT is Less Accurate than Echocardiography: Comparison with Surgical Findings
Authors: Nina Ghosh, Halia Al-Shehri, Kwan Chan, Thierry Mesana, Vincent Chan, George A Wells, Li Chen, Yeung Yam, Benjamin Chow
Journal: Circulation (2010)

Introduction: Cardiac CT is rapidly gaining acceptance for the detection of coronary artery disease. There is limited data supporting its use for the assessment of valve anatomy. A single imaging m...
Abstract 857: Metal oxide nanoparticles as adjuvant for radiation therapy
Authors: Nadine Wiesmann, Martin Kluenker, Wolfgang Tremel, Juergen Brieger
Journal: Cancer Research (2018)

Abstract Background: Radiation therapy comprises a fundamental component of modern tumor treatment. Unfortunately, its success is limited by the development of radiation resistances. The emerging field of nanotechnology offers great opportunities for diagnosing, imaging, as well as treating cancer. Metal oxide nanoparticles in particular zinc oxide nanoparticles (ZnO-NP) have been shown to display a selective cytotoxic effect on tumor cells via a yet unknown mechanism. Most likely the generation of reactive oxygen species (ROS), breakdown of mitochondria and DNA damage are involved. The success of radiation therapy equally relies on the generation of ROS, which develop their cytotoxic potential by damaging DNA, proteins and membranes in a fashion that exceeds the repair capacity of tumor cells. Thus, our aim was to evaluate the applicability of ZnO-NP as radiosensitizer to restore the response of tumor cells to radiation therapy. Methods: An AlamarBlueTM assay was used to evaluate the cellular metabolic activity (CMA) of A549 adenocarcinoma cells after treatment with ZnO-NP. To assess cellular viability and cell death a flow cytometric apoptosis assay was applied and genotoxicity of ZnO-NP was analysed by γH2AX foci analysis. The performance of ZnO-NP as radiosensitizer was assessed by a colony formation assay (CFA). Results: We were able to show that ZnO-NP-mediated cytotoxicity is conveyed by dissolved Zn2+ ions as well as by the particles themselves. Treatment with ZnO-NP resulted in double-strand breaks (DSB) of the DNA measured by γH2AX foci analysis. The apoptosis assay could show induction of apoptosis in A549 cells after treatment with 100 µg/ml ZnO-NP for four hours. The colony formation assay showed that irradiation with 2 or 4 Gray, according to dosages that are typically applied in clinical settings, in combination with ZnO-NP treatment could enhance tumor cell death and reduce clonogenic survival. This revealed that ZnO-NP could improve the success of radiation therapy. Conclusions: Our study proves that ZnO-NP exert a cytotoxic and genotoxic effect on human tumor cells. Additionally, we could show, that ZnO-NP are able to serve as radiosensitizer. Combined treatment of human tumor cells with ZnO-NP and irradiation resulted in reduction of tumor cell survival. Since nanoparticles can in principle be targeted selectively to tumor tissue, ZnO-NP could be used to specifically sensitize tumor cells for irradiation while sparing healthy tissue. All in all, the study shows that ZnO-NPs could be a promising antitumor agent. Citation Format: Nadine Wiesmann, Martin Kluenker, Wolfgang Tremel, Juergen Brieger. Metal oxide nanoparticles as adjuvant for radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 857.
Abstract 16179: A Novel Protocol for Dispatcher Assisted Cardiopulmonary Resuscitation Improves Quality of Cardiopulmonary Resuscitation: A Randomized Controlled Simulation Study
Authors: Stinne E Rasmussen, Mette A Nebsbjerg, Katrine Bjørnshave, Lise Q Krogh, Kristian Krogh, Jonas A Povlsen, Ingunn S Riddervold, Thorbjørn Grøfte, Hans Kirkegaard, Bo Løfgren
Journal: Circulation (2015)

Introduction: Dispatcher assisted CPR (DA-CPR) increases rate and quality of CPR and improves survival. Several studies have shown that changing one element in a dispatcher’s protocol improve CPR performance. Whether one improvement counter the effect of another improvement is unknown and the effect of combining several beneficial elements in a dispatcher protocol remains to be clarified. Hypothesis: A novel DA-CPR protocol, combining several single elements improving CPR performance, is superior to a standard DA-CPR protocol. Methods: Based on previous research and pilot studies a novel DA-CPR protocol including new wording on chest compression depth and hand position, the use of a metronome, provision of encouragements and introducing a 10-sec rest per minute was developed. Subsequently, laypersons were randomized to perform chest compression-only DA-CPR on a manikin with either the novel DA-CPR protocol or a standard DA-CPR protocol. Data on CPR quality was collected on video recordings and from the manikin and evaluated by two assessors blinded to the experimental groups. The primary outcome was a composite endpoint of time to first compression, hand position, compression depth and -rate and hands-off time, which were rated separately each minute and merged into an overall score (max 22 points). Results: 128 laypersons were included in the study. The novel protocol (n=61, three were excluded) significantly improved the CPR quality compared to the standard protocol (n=64) (mean (SD)): 18.6 (1.4) points vs. 17.5 (1.7) points, p&lt;0.001. The novel protocol resulted in significantly deeper (mean (SD): 58 (12) mm vs. 52 (13) mm, p=0.02) and faster (mean (SD): 114 (11) min-1 vs. 110 (13) min-1, p=0.04) compressions when compared to the standard protocol. The novel protocol resulted in shorter time to first compression (median (IQR): 65 (59, 70) sec vs. 72 (66, 81) sec, p&lt;0.001) and better hand position for compressions (61% vs. 36%, p=0.01) compared to the standard protocol. As intended, hands-off time per minute was prolonged with the novel protocol (median (IQR): 6 (5, 7) sec vs. 0 (0, 1) sec). Conclusions: In a simulated cardiac arrest scenario, a novel protocol for DA-CPR was superior to a standard DA-CPR protocol. Both protocols resulted in high quality CPR.
New Editorial Board Member–July 2018
Authors: Melina R. Kibbe
Journal: JAMA Surgery (2018)

JAMA Surgery thanks Karl Bilimoria, MD, MS, for his extraordinary service and contributions to the journal as a member of the Editorial Board. Effective July 1, 2018, JAMA Surgery is pleased to announce the appointment of Amir A. Ghaferi, MD, MS, to our Editorial Board.
Abstract 2662: Indenoisoquinoline topoisomerase I inhibitors target the DNA G-quadruplex formed in the c-Myc promoter and cause MYC downregulation
Authors: Kaibo Wang, Mohamed S. A. Elsayed, Guanhui Wu, Mark Cushman, Danzhou Yang
Journal: Cancer Research (2018)

Abstract The inhibition of DNA topoisomerase I (Top1) has proven to be a successful approach toward the design of anticancer agents. Indenoisoquinoline derivatives have been designed and developed as Top1 inhibitors and can overcome some shortcomings associated with the camptothecin Top1 inhibitors, resulting in three indenoisoquinoline compounds, indotecan (LMP 400), indimitecan (LMP776), and LMP744 entering Phase I clinical trials at the National Cancer Institute. However, some active indenoisoquinolines did not show potent Top1 inhibition, suggesting a separate mechanism of action. c-Myc is one of the most commonly deregulated genes in human cancers; a DNA G-quadruplex (G4) formed in the proximal promoter region of c-Myc has been found to function as a transcriptional silencer and be amenable to small molecule targeting. As indenoisoquinolines share structure similarity to our c-Myc G-quadruplex (MycG4)-interactive compounds, we hypothesized that indenoisoquinolines could stabilize MycG4 and downregulate MYC transcription. Using a fluorescence resonance energy transfer (FRET) assay, we examined the MycG4 stabilization activity of 56 indenoisoquinoline compounds that we previously developed as Top1 inhibitors. Notably, 26 of the 56 compounds decreased the fluorescence intensity by at least 50%, and the 10 most potent compounds reduced fluorescence intensities by over 70%, indicating that these indenoisoquinolines are effective MycG4 stabilizers. The identified compounds were further characterized by fluorescence anisotropy, circular dichroism, and nuclear magnetic resonance for MycG4 interactions, followed by western blot assays for MYC downregulation. Significantly, the compounds with good MycG4 binding activity and affinity exhibited significant dose-dependent reduction of MYC expression, indicating that targeting the c-Myc promoter G-quadruplex is a likely mechanism of action for these active anticancer compounds. Furthermore, some active indenoisoquinolines exhibited both MYC downregulation and Top1 inhibition, suggesting that dual targeting c-Myc G-quadruplex and Top1 may represent a novel mechanism of action for anticancer drug design. Citation Format: Kaibo Wang, Mohamed S. A. Elsayed, Guanhui Wu, Mark Cushman, Danzhou Yang. Indenoisoquinoline topoisomerase I inhibitors target the DNA G-quadruplex formed in the c-Myc promoter and cause MYC downregulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2662.
Abstract 11539: Impact of Adipose Tissue Composition on Cardiovascular Risk Assessment
Authors: AyakoKunimura, TadayukiUetani, TakashiKataoka, MasahiroTakeshita, KazuhiroHarada, SatoshiOkumura, NorihiroShinoda, KenHarada, BunichiKato, MasatakaKato, NobuyukiMarui, MichioNanki, TatsuakiMatsubara, HidekiIshii, TetsuyaAmano, ToyoakiMurohara
Journal: Circulation (2014)

Background: Visceral adipose tissue (VAT) , unlike subcutaneous adipose tissue (SAT), has been shown to be highly correlated with cardiovascular risk factors. The aim of this study was to evaluate the predictive value of adipose tissue composition measured by computed tomography for cardiovascular outcome. Method: 369 consecutive patients without history of cardiovascular disease who underwent 64-slice computed tomography angiography (CTA) were recruited. The ratio of visceral adipose tissue to the total adipose tissue (%VAT) was calculated as VAT/ (VAT + SAT) х 100. Patients were divided into three groups in accordance with tertiles of %VAT (tertile1, <35.1%; tertile2, 35.1 to 45.0%; tertile3, 45.1%≤). The investigated risk factors were hypertension, hyperglycemia, and dyslipidemia. We analyzed the incidence of major adverse cardiac events (MACE), including cardiovascular death, myocardial infarction, and any revascularization. Result: The rate of patients who have two or more concomitant risk factors wa...
Abstract 5260: Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort
Authors: ShaoMing Wang, Neal D. Freedman, Erikka Loftfield, Xing Hua, Christian C. Abnet
Journal: Cancer Research (2018)

Abstract Objective: The 2016 WCRF Continuous Update Project reported that consumption of alcoholic drinks probably causes gastric cancer, but the magnitude of the association was small, there was moderate heterogeneity among the studies included in the meta-analysis, and most studies were from Asian populations, with only 401 cases from North American studies. Therefore, we re-evaluated the association between alcohol intake and gastric cancer in a large US cohort that has accrued more than 1300 gastric cancer cases. Methods: We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA) in 490,605 members aged 50-71 years at baseline in the NIH-AARP Diet and Health Study cohort. Alcohol consumption was assessed during the baseline questionnaire in 1995/1996 and evaluated as grams of ethanol intake and as a categorical variable: never, up to or including one drink/day, one to three drinks/day, and greater than three drinks/day. We used Cox proportional hazard regression to calculate the hazard ratios and 95% confidence intervals for associations between alcohol intake and risk of gastric adenocarcinomas with adjustment for several potential confounders. Results: Through 2011, 662 incident cases of GCA and 713 of GNCA occurred in the cohort. We found no association between higher alcohol consumption and GCA or GNCA, regardless of whether analyzed as total alcoholic beverage intake or the individual beverage types of beer, wine and liquor and no evidence for a dose-response. Furthermore, we observed no association by stratum of sex, ethnic group, educational level, or smoking status. Although there were no overall associations, we found some evidence for lower risk of GNCA among people who drank up to one drink per day (HR=0.81, 95%CIs:0.67-0.97) compared to nondrinkers. Conclusion: Alcohol consumption was not associated with increased risk of gastric cardia adenocarcinoma or gastric non-cardia adenocarcinoma in this large US prospective cohort. Citation Format: ShaoMing Wang, Neal D. Freedman, Erikka Loftfield, Xing Hua, Christian C. Abnet. Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma: A prospective analysis from the NIH-AARP Diet and Health cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5260.
Abstract 2849: Biodynamic imaging predicts response of breast cancer patients to neoadjuvant chemotherapy
Authors: John J. Turek, David D. Nolte, Ran An
Journal: Cancer Research (2018)

Abstract The goal of this research was to determine if biodynamic imaging (BDI) and frozen breast cancer tumors from tissue banks could be used to retrospectively assess response to chemotherapy and identify the more chemoresistant patients. Neoadjuvant chemotherapy (NAC) is a common protocol for breast cancer patients prior to surgery. Many patients will respond to initial chemotherapy, but there is a significant percentage of patients that do not receive a benefit from NAC due to chemoresistance. Accurate prediction of chemoresistance prior to therapy, could enhance the effectiveness of NAC by allowing for better drug selection. BDI uses Doppler detection of light scattered by intracellular motion in living tissue, and several xenograft, and clinical studies have shown that this phenotypic profiling method is a highly accurate predictor of resistance to chemotherapy. Frozen, clinically annotated breast cancer samples were obtained from several tissue banks. All of the patients received adriamycin-cyclophosphamide and paclitaxel (AC-T) neoadjuvant chemotherapy prior to surgery. The samples were rapidly thawed and 1mm3 pieces were placed in tissue culture medium in a 96 well plate, sealed with a gas permeable membrane, and 6 replicates for each drug treatment assayed over an 18 hour period. Drugs tested were the AC combination, and also the individual drugs (adriamycin, 4-hydroxycyclophosphamide, and paclitaxel). A negative drug vehicle control was 0.1% DMSO in growth medium, and vincristine was used as a positive control. For the analysis, patients were classified as sensitive or resistant based upon the clinically annotated pathology reports. The BDI spectral data for each drug treatment was analyzed using a machine learning algorithm to identify patterns in the frequency vector biomarkers for each patient using a combination of a similarity matrix and a linear separability analysis using a neural net perceptron. The neural net perceptron and hold-out cross validation of BDI spectral data correctly identified all patients as sensitive or resistant. Frozen samples from tissue banks contain enough viable cells to evaluate drug response using BDI. This makes it possible to conduct retrospective studies on chemoresistance using frozen banked tissue samples and also makes it possible to study the relationship between genotype to chemo-phenotype. Supported by Animated Dynamics, Inc. Citation Format: John J. Turek, David D. Nolte, Ran An. Biodynamic imaging predicts response of breast cancer patients to neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2849.
Possible Mechanism(s) of Arachidonic Acid–Induced Intracellular Acidosis in Rat Cardiac Myocytes
Authors: Mei-LinWu, Chih-ChiangChan, Ming-JaSu
Journal: Circulation Research (2000)

Abstract—Arachidonic acid (AA) and other nonesterified fatty acids (FAs) have been shown to exert harmful effects during cardiac ischemia. By continuously measuring intracellular pH (pHi) changes in neonatal and adult cardiac myocytes, we have found, for the first time, that 10 μmol/L AA induces a substantial intracellular acidosis (0.3 to 0.4 pH units). We have ruled out the possibilities that the AA-induced acidosis is caused by (1) inhibition or stimulation of the pHi regulators, (2) protein kinase C activation or the generation of AA metabolites or free radicals, or (3) activation of NADPH oxidase or an inward H+ current. The AA-induced acidosis fits to a simple diffusion mechanism, as proposed by Kamp and Hamilton (flip-flop model) for artificial phospholipid bilayers. The important properties found in the cardiac myocyte are that (1) the initial rate of acid flux (JH) increases with the AA concentration (2 to 50 μmol/L), (2) FAs with a −COOH group (eg, AA, oleic acid, and linoleic acid) induce intra...
Abstract 17051: Impact of Decreased Ankle-brachial Index on In-hospital Bleeding Complication and Long-term Prognosis in Patients With Acute Coronary Syndrome
Authors: Takuya Nakahashi, Kenji Sakata, Hidenobu Terai, Yuki Horita, Masatoshi Ikeda, Masanobu Namura, Masayuki Takamura, Masa-aki Kawashiri, Masakazu Yamagishi
Journal: Circulation (2017)

Introduction: Coexistence of peripheral artery disease (PAD) in patients with acute coronary syndrome (ACS) associates higher incidence of bleeding complication and adverse events after PCI. Although the ankle-brachial index (ABI) is used in a simple, non-invasive diagnosis of PAD, few data exist regarding bleeding risk score which contains ABI in patients with undergoing PCI. Hypothesis: The combination of ABI and classical risk factors of bleeding complication would improve the predictive ability of outcome. Methods: Consecutive 843 patients (652 men; mean age, 68±12) with ACS who underwent PCI and ABI examination were analyzed. The presence of PAD was defined as ABI <0.9. The primary endpoint was 30-day bleeding which was defined according to Bleeding Academic Research Consortium classification grade ≥3. Additionally, we analyzed the major adverse cardiovascular event (MACE) as secondary endpoint which was defined as all-cause death, myocardial infarction, and stroke. Results: There were 140 (16.7%) pa...
IgD-activated mast cells induce IgE synthesis in B cells in nasal polyps
Authors: Guan-Ting Zhai, Hai Wang, Jing-Xian Li, Ping-Ping Cao, Wen-Xiu Jiang, Jia Song, Yin Yao, Zhi-Chao Wang, Zhe-Zheng Wang, Meng-Chen Wang, Bo Liao, Qi-Miao Feng, Xiang Lu, Heng Wang, Peisong Gao, Zheng Liu
Journal: Journal of Allergy and Clinical Immunology (2018)
Differential Behaviors of Atrial Versus Ventricular Fibroblasts
Authors: BrettBurstein, EricLibby, AngelinoCalderone, StanleyNattel
Journal: Circulation (2008)

Background— In various heart disease paradigms, atria show stronger fibrotic responses than ventricles. The possibility that atrial and ventricular fibroblasts respond differentially to pathological stimuli has not been examined. Methods and Results— We compared various morphological, secretory, and proliferative response indexes of canine atrial versus ventricular fibroblasts. Cultured atrial fibroblasts showed faster cell surface area increases, distinct morphology at confluence, and greater α-smooth muscle actin expression than ventricular fibroblasts. Atrial fibroblast proliferation ([3H]thymidine incorporation) responses were consistently greater for a range of growth factors, including fetal bovine serum, platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, endothelin-1, and transforming growth factor-β1. Normal atrial tissue showed larger myofibroblast density compared with ventricular tissue, and the difference was exaggerated by congestive heart failure. Congesti...