tbuckley/cabot-search huggingface dataset:
Abstract 4427: Preparation and mechanism of polyethyleneimine coated miRNA let-7a microspheres
Authors: Honglin Lai, Weixiao An, Yangyang Zhang, Xiukun Lin, Shousong Cao
Journal: Cancer Research (2018)

Abstract Recent evidence demonstrates that microRNAs (miRNAs) are associated with cancer development and have the potential to be used as anticancer agents. However, the application of miRNAs as clinical cancer drugs has been limited due to their unstability at room temperature. Moreover, miRNAs are negatively charged and excluded by cytomembrane, which has the same polarity. Therefore, miRNAs are difficult to enter cancer cells to exhibit their anticancer effects. In order to solve the problem, we changed the polarity of miRNA let-7a, a member of the second identified miRNA let-7 families, by coating with a bioavailable polymer, polyethylenimine (PEI) using nanotechnology, to alter the charge of miRNA let-7a for positive charge so easily connecting with the anionic residues of cancer cell surfaces. Therefore, miRNA let-7a could easily entered cells through endocytosis. In addition, we performed formaldehyde denaturing SDS-PAGE analysis to determine the stability of miRNA let-7a, and we found the stability of miRNA let-7a has been significantly increased due to microspheres formation. MiRNA let-7a microspheres have showed potent cytotoxicity against a variety of cancer cells including HCT-116, A875, A549, and 4T1 cells with the IC50 as 31.77, 54.34, 44.35, 43.18 pmol/l, respectively by CCK-8 kit analysis. We also found that miRNA let-7a microspheres are able to induce cell apoptosis by promoting the expression of apoptosis-related genes Caspase 3, Caspase 9 and PARP in HCT-116 and A875 cells. Our findings may provide that miRNA let-7a microspheres may be developed as a novel anticancer agents in cancer therapy. Citation Format: Honglin Lai, Weixiao An, Yangyang Zhang, Xiukun Lin, Shousong Cao. Preparation and mechanism of polyethyleneimine coated miRNA let-7a microspheres [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 4427.
Abstract 3998: Integrative molecular analysis uncovers key molecules and signaling pathways regulated by RKIP in gastrointestinal stromal tumors (GISTs)
Authors: Nathália C. Campanella, Matias Melendez, Leticia Ferro Leal, Adriane Feijo Evangelista, Vitor Marcel Faça, Rui Manuel Reis
Journal: Cancer Research (2018)

Abstract Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor on the gastrointestinal tract, and are characterized by hotspot mutations in KIT and PDGFRA genes, which are predictive of imatinib-based therapy response. We showed previously that RKIP, a metastasis suppressor gene, is lost in about 17% of GIST, and it was associated with an adverse outcome. RKIP is plays a pivotal role in several signaling pathways, namely MAPK, NF-κβ, and GSK3β however a multidimensional integrative analysis to uncover its biological impact was never done in cancer and in particular in GIST. Experimental procedures: We established a RKIP knockout GIST cell line (GIST-T1 KO) by CRISPR/Cas9 system. The differential gene and microRNA expression profile between GIST-T1 RKIP-KO and GIST-T1 negative control cells were assessed using the NanoString nCounter® technology and the nCounter® PanCancer Pathways and nCounter® miRNA Expression assays (NanoString Technologies). All procedures including sample preparation (100 ng of RNA), hybridization, detection and scanning were performed according to manufacture's instructions (NanoString Technologies). In a second step, we performed a global proteomic analysis using the Acquity UPLC M-Class chromatography system (Waters Co) linked to the mass spectrometer Synapt G2-Si (Waters Co). The protein identification and quantification were performed in Progenesis QI for Proteomics (Waters Co) software. Results: The nCounter gene expression analysis showed 56 genes differentially expressed: 18 downregulated and 38 upregulated genes in RKIP KO cells. The altered genes are especially involved in PI3k-AKT, MAPK and Ras signaling pathways. The global proteomic characterization showed 50 proteins differentially expressed: 5 were downregulated and 44 upregulated proteins in RKIP KO cells. In microRNA expression profile analysis we found 133 downregulated microRNAs in RKIP KO cells. Taking together, these findings uncover new molecules that are going to screen in a cohort of GIST patients. Conclusion: For the first time, using a multidimensional integrative analysis we identified driver candidates and pathways, which will contribute the uncovered the biological role of RKIP in cancer. Citation Format: Nathália C. Campanella, Matias Melendez, Leticia Ferro Leal, Adriane Feijo Evangelista, Vitor Marcel Faça, Rui Manuel Reis. Integrative molecular analysis uncovers key molecules and signaling pathways regulated by RKIP in gastrointestinal stromal tumors (GISTs) [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 3998.
AI system interprets eye scans as accurately as top specialists
Authors: Jacqui Wise
Journal: BMJ (2018)

An artificial intelligence (AI) system recommended the correct referral decision for 53 eye diseases with 94% accuracy—matching the performance of top eye experts—according to new research published in Nature Medicine .1

The technology, which has been developed by researchers at Moorfields Eye Hospital NHS Foundation Trust, DeepMind Health, and University College London, needs to go through clinical trials and gain regulatory approval before it can be routinely used in hospitals. It is hoped, however, that the AI system could speed up the referral process for patients who urgently need treatment for diseases such as age related macular degeneration and diabetic retinopathy.

Optical coherence tomography (OCT) scans are used to help diagnose eye conditions. These are 3D images which provide a detailed map of the back of the eye but they are difficult to read and need …
Abstract 13939: Cardiac Resynchronization Improves Cardiac Sodium Channel mRNA Splicing Most in Patients With Severe Heart Failure
Authors: Ning Jiang, Anyu Zhou, Hafiz Imran, Guangbin Shi, Bahaa Kaseer, Vincent Siu, Jharendra Rijal, Antony Chu, David Donaldson, Michael Kim, Malcolm Kirk, Binu Philips, Michael Orlov, Samuel C Dudley
Journal: Circulation (2016)

Introduction: Heart failure (HF) downregulates full-length cardiac sodium channel (SCN5A) mRNA and upregulates the splicing variant D (VD), which encodes a prematurely truncated, nonfunctional channel. Recently, we have shown that the ratio of circulating VD to full-length mRNA can predict the risk of sudden death. Cardiac resynchronization therapy (CRT) improves heart function and decreases arrhythmic events. Nevertheless, the mechanisms are unclear. Hypothesis: We tested whether CRT altered circulating full-length SCN5A mRNA and VD and further investigated its correlation with clinical parameters in HF. Methods: HF patients with new implantable cardioverter-defibrillators (ICDs) for primary prevention were enrolled. Circulating SCN5A and VD levels at baseline and at a follow-up visit were measured and compared using the ratio of VD to total SCN5A transcripts. The change of VD was expressed as the difference between the proportion of VD levels at baseline and at a follow-up visit. Results: A total of 81 HF patients were enrolled. At enrollment, patients with lower ejection fraction (EF) (≤30%) had higher circulating VD levels (0.80±0.11 vs. 0.73±0.07, P&lt;0.05). After a median follow-up of 235 days, the VD ratio significantly improved (0.84±0.08 vs. 0.74±0.10, P&lt;0.01) in patients receiving CRT. In patients without CRT, the VD ratio had significantly increased (0.77±0.07 vs 0.84±0.05, P&lt;0.05). In patients with CRT, the change of the VD ratio significantly correlated with left ventricular end systolic diameter (r=0.853, p&lt;0.01), EF (r=-0.643, p&lt;0.05) and ischemic cardiomyopathy (r=0.645, p&lt;0.05). Conclusions: CRT decreased the proportion of nonfunctional sodium channels, which may explain the lower arrhythmic risk with CRT therapy. Furthermore, the improvement was more prominent in patients with left ventricular dilation, lower EF and ischemic cardiomyopathy.
Adrenomedullin Reduces Endothelial Hyperpermeability
Authors: StefanHippenstiel, MartinWitzenrath, BerndSchmeck, AndreasHocke, MathiasKrisp, MatthiasKrüll, JoachimSeybold, WernerSeeger, WolfgangRascher, HartwigSchütte, NorbertSuttorp
Journal: Circulation Research (2002)

Endothelial hyperpermeability induced by inflammatory mediators is a hallmark of sepsis and adult respiratory distress syndrome. Increased levels of the regulatory peptide adrenomedullin (ADM) have been found in patients with systemic inflammatory response. We analyzed the effect of ADM on the permeability of cultured human umbilical vein endothelial cell (HUVEC) and porcine pulmonary artery endothelial cell monolayers. ADM dose-dependently reduced endothelial hyperpermeability induced by hydrogen peroxide (H2O2), thrombin, and Escherichia coli hemolysin. Moreover, ADM pretreatment blocked H2O2-related edema formation in isolated perfused rabbit lungs and increased cAMP levels in lung perfusate. ADM bound specifically to HUVECs and porcine pulmonary artery endothelial cells and increased cellular cAMP levels. Simultaneous inhibition of cAMP-degrading phosphodiesterase isoenzymes 3 and 4 potentiated ADM-dependent cAMP accumulation and synergistically enhanced ADM-dependent reduction of thrombin-induced hyp...
Activated RhoA Stimulates c-fos Gene Expression in Myocardial Cells
Authors: TomomiUeyama, TsuyoshiSakoda, SeinosukeKawashima, EijiHiraoka, Ken-ichiHirata, HozukaAkita, MitsuhiroYokoyama
Journal: Circulation Research (1997)

Abstract Rho regulates various cell functions, including cell morphology and motility. However, the functional role of Rho on the signaling pathway in myocardial cells (MCs) is unknown. In the present study, we attempted to explore the mode of Rho action for c-fos gene expression in MCs. Expression of the c-fos promoter/enhancer linked to the luciferase reporter gene (c-fos luciferase) was stimulated by the wild type of RhoA and the point-mutated active form of RhoA (RhoA Val14) but not the biologically inactive effector domain mutant of RhoA. Rho GDP dissociation inhibitor inhibited the action of RhoA on c-fos luciferase expression. The deletion analysis revealed that the c-fos serum response element (SRE) and the 12-O-tetradecanoylphorbol-13-acetate response element (TRE) mainly account for c-fos luciferase expression by RhoA Val14. The c-fos SRE mutant, which contains an intact binding site for the serum response factor but lacks the ternary complex factor binding site, was activated by RhoA Val14. The...
Abstract 9729: Should HF Preserved-Ejection Fraction Patients Participate in a HF Program?
Authors: LindaKelly, GreggSteahr, BrendaHott
Journal: Circulation (2014)

Introduction: Optimal treatment regimens for individuals with Heart Failure preserved Ejection Fraction (HFpEF) have yet to be defined and these patients comprise nearly half the heart failure (HF) population. We present outcomes of this patient population from our first year in a heart failure program (HFP). Hypothesis: HFpEF patients will benefit as much as heart failure reduced ejection fraction (HFrEF) patients from a HFP. Methods: Retrospective review of 142 HFP patients (HFpEF n=56, HFrEF n=86). Baseline, 3 and 6 month assessments of NYHA class, six minute walk, and Minnesota Living with Heart Failure Questionnaire (MLWHF) were completed. Three month hospital admissions before and after HFP enrollment were reviewed. The HFP provides an inpatient consult service for acutely decompensated HF patients and weekly interdisciplinary rounds. Transition of care with telemonitoring for 30 days post discharge assessing med reconciliation, weight, BP, signs of worsening HF and treatment as needed . The outpati...
Evaluation of a Novel Rule-Out Myocardial Infarction Protocol Incorporating High-Sensitivity Troponin T in a US Hospital
Authors: Rebecca Vigen, Patricia Kutscher, Fernabelle Fernandez, Amy Yu, Bryan Bertulfo, Ibrahim A. Hashim, Kyle Molberg, Deborah B. Diercks, Jeffery C. Metzger, Jose Soto, Dergham Alzubaidy, Lorie Thibodeaux, Jose A. Joglar, James A. de Lemos, Sandeep R. Das
Journal: Circulation (2018)
Abstract P015: Plasma Brain Natriuretic Peptide Concentration Is Inversely Associated With Prevalent Metabolic Syndrome and Metabolic Syndrome Components: Findings From the Jackson Heart Study
Authors: Harsha Nagarajarao, Solomon K Musani, Vasan S Ramachandran, Aurelian Bidulescu, Herman A Taylor, Ervin R Fox
Journal: Circulation (2012)

Introduction: There is emerging evidence that brain natriuretic peptide (BNP) may play a role in human metabolism. Suppressed concentrations in BNP in obese individuals may contribute to clinical phenotypes of metabolic syndrome. There is limited data on the relation of BNP to metabolic syndrome in African Americans. Methods: To assess the association between plasma brain natriuretic peptide (BNP) concentration and metabolic syndrome (MetS) and MetS risk factors in blacks, we analyzed cross-sectional data from 3,729 Jackson Heart Study participants free of heart failure (mean age, 54 years; 64% women). We performed sex-specific Tobit regression analysis on log transformed BNP to account for the left censored BNP distribution and adjusted for clinical and echocardiographic variables. Prevalence of MetS was 44% and 35% in women and men, respectively. We estimated percent changes for the underlying variables by back-transformation. Results: Plasma BNP concentration was inversely associated with metabolic syndrome components (fasting glucose and waist circumference in both men and women; and triglycerides in women). Sex-specific multivariable adjusted BNP concentrations were significantly lower in subjects with MetS than those without. In men, BNP concentration was 35% lower (P &lt; 0.0001); and in women it was 31% lower (P &lt; 0.0001). Men and women with insulin resistance represented by elevated homeostasis assessment model (HOMA-IR) index had significantly (P &lt; 0.0001) lower BNP concentration compared to those with low HOMA-IR index. Discussion and Conclusion: We found in a community based cohort of African Americans a significant relation of low BNP concentration to MetS and individual components of MetS. This data supports a growing body of evidence that BNP plays a potential crucial role in total body metabolism.
CD44 Binds to Macrophage Mannose Receptor on Lymphatic Endothelium and Supports Lymphocyte Migration via Afferent Lymphatics
Authors: MarkoSalmi, MarikaKarikoski, KatiElima, PiaRantakari, SirpaJalkanen
Journal: Circulation Research (2013)

Rationale:Macrophage mannose receptor (MRC) is one of the few molecules known to be involved in lymphocyte trafficking via the lymphatic vessels. In endothelial cells of efferent lymphatics, it binds L-selectin on lymphocytes. In afferent lymphatics, MRC mediates trafficking of both normal and malignant L-selectin–negative cells to the draining lymph nodes. Objective:This work was designed to search for additional lymphocyte ligands of MRC to elucidate how lymphocytes migrate into the draining lymph nodes. Methods and Results:Using immunoprecipitation and binding studies with natural and recombinant proteins, we show that MRC and CD44 can interact with each other. Fine mapping revealed that the cysteine-rich domain of MRC binds to the chondroitin sulfate side chains of CD44. In vivo homing experiments with MRC- and CD44-deficient mice verified that MRC and CD44 function as a receptor-ligand pair in supporting lymphocyte migration via the afferent lymphatics into the draining lymph nodes. Conclusions:These...
PPARα Activators Inhibit Tissue Factor Expression and Activity in Human Monocytes
Authors: NikolausMarx, NigelMackman, UweSchönbeck, NurcanYilmaz, VinzenzHombach, PeterLibby, JorgePlutzky
Journal: Circulation (2001)

Background—Tissue factor (TF), expressed on the surface of monocytes and macrophages in human atherosclerotic lesions, acts as the major procoagulant initiating thrombus formation in acute coronary syndromes. Peroxisome proliferator–activated receptor-α (PPARα), a nuclear receptor family member, regulates gene expression in response to certain fatty acids and fibric acid derivatives. Given that some of these substances reduce TF activity in patients, we tested whether PPARα activators limit TF responses in human monocytic cells. Methods and Results—Pretreatment of freshly isolated human monocytes or monocyte-derived macrophages with PPARα activators WY14643 and eicosatetraynoic acid (ETYA) led to reduced lipopolysaccharide (LPS)-induced TF activity in a concentration-dependent manner (maximal reduction to 43±8% with 250 μmol/L WY14643 [P 0.05, n=3]). Two different PPARγ activators (15-deoxy_Δ12,14-prostaglandin J2 and BRL49653) lacked similar effects. WY1464...
Reply to Mummadi <i>et al.</i>: Overfitting and Use of Mismatched Cohorts in Deep Learning Models: Preventable Design Limitations
Authors: Germán González, Samuel Y. Ash, Raúl San José Estépar, George Washko
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The electronic health record (EHR) is a powerful tool with the potential to facilitate communication across healthcare systems.By informing clinical practice, administrative operations, and research initiatives, the EHR has the potential to support the needs of diverse stakeholders, including clinicians, patients, caregivers, researchers,
Abstract 363: Role of the SAGA histone acetylation module in lung cancer
Authors: Lisa Maria Mustachio, Jason Roszik, Sharon YR Dent
Journal: Cancer Research (2018)

Abstract Lung cancer causes the highest mortality in cancer-related deaths. Definition of novel molecular targets is needed since these cancers often become resistant to existing therapies. Epigenetic modifications may provide such targets. Recent reports suggest that the histone acetyltransferase (HAT) module within the transcriptional coactivator SAGA complex plays a role in cancer, creating a new link between epigenetic regulators and this disease. We are working to define the role of the SAGA HAT protein GCN5 in the regulation and function of oncogenes in lung cancers. Since our prior work indicates that GCN5 serves as a coactivator for MYC target genes, we hypothesize that inhibition of GCN5 will reduce lung oncogenesis by suppressing MYC functions. We also propose that inhibition of GCN5 will reduce lung cancer formation and progression in mouse models of lung cancer. Our preliminary data indicate that both GCN5 and MYC expression levels are upregulated and positively associated in mouse and human lung cancers. Both proteins are also associated with MYC target genes in lung cancer tissues. Inhibition of the GCN5 active site or bromodomain significantly (p &amp;lt; 0.05) reduces cell proliferation compared to normal lung epithelium cells. Studies investigating how GCN5 inhibition affects other lung cancer phenotypes are underway. Specific genes and pathways affected by GCN5 loss will be determined using RNA-Seq and RPPA assays to identify mechanisms behind observed phenotypes. In addition, we will determine whether knockout of Gcn5 reduces lung formation and progression in the KrasLA2 lung cancer mouse model. Our ongoing studies will determine whether targeting GCN5 represses multiple oncogenic pathways in cancer and whether it inhibits oncoproteins difficult to directly target, such as MYC. We expect that our findings will highlight the importance of epigenetic regulators in carcinogenesis and extend beyond our current research focus to other cancer types. Citation Format: Lisa Maria Mustachio, Jason Roszik, Sharon YR Dent. Role of the SAGA histone acetylation module in lung cancer [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 363.
Vitamin D Supplementation in Pregnancy and Lactation and Infant Growth
Authors: Daniel E. Roth, Shaun K. Morris, Stanley Zlotkin, Alison D. Gernand, Tahmeed Ahmed, Shaila S. Shanta, Eszter Papp, Jill Korsiak, Joy Shi, M. Munirul Islam, Ishrat Jahan, Farhana K. Keya, Andrew R. Willan, Rosanna Weksberg, Minhazul Mohsin, Qazi S. Rahman, Prakesh S. Shah, Kellie E. Murphy, Jennifer Stimec, Lisa G. Pell, Huma Qamar, Abdullah Al Mahmud
Journal: New England Journal of Medicine (2018)

It is unclear whether maternal vitamin D supplementation during pregnancy and lactation improves fetal and infant growth in regions where vitamin D deficiency is common.We conducted a randomized, double-blind, placebo-controlled trial in Bangladesh to assess the effects of weekly prenatal vitamin D supplementation (from 17 to 24 weeks of gestation until birth) and postpartum vitamin D supplementation on the primary outcome of infants' length-for-age z scores at 1 year according to World Health Organization (WHO) child growth standards. One group received neither prenatal nor postpartum vitamin D (placebo group). Three groups received prenatal supplementation only, in doses of 4200 IU (prenatal 4200 group), 16,800 IU (prenatal 16,800 group), and 28,000 IU (prenatal 28,000 group). The fifth group received prenatal supplementation as well as 26 weeks of postpartum supplementation in the amount of 28,000 IU (prenatal and postpartum 28,000 group).Among 1164 infants assessed at 1 year of age (89.5% of 1300 pregnancies), there were no significant differences across groups in the mean (±SD) length-for-age z scores. Scores were as follows: placebo, -0.93±1.05; prenatal 4200, -1.11±1.12; prenatal 16,800, -0.97±0.97; prenatal 28,000, -1.06±1.07; and prenatal and postpartum 28,000, -0.94±1.00 (P=0.23 for a global test of differences across groups). Other anthropometric measures, birth outcomes, and morbidity did not differ significantly across groups. Vitamin D supplementation had expected effects on maternal and infant serum 25-hydroxyvitamin D and calcium concentrations, maternal urinary calcium excretion, and maternal parathyroid hormone concentrations. There were no significant differences in the frequencies of adverse events across groups, with the exception of a higher rate of possible hypercalciuria among the women receiving the highest dose.In a population with widespread prenatal vitamin D deficiency and fetal and infant growth restriction, maternal vitamin D supplementation from midpregnancy until birth or until 6 months post partum did not improve fetal or infant growth. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01924013 .).
A Bayesian Model to Predict Survival After Left Ventricular Assist Device Implantation
Authors: Manreet K. Kanwar, Lisa C. Lohmueller, Robert L. Kormos, Jeffrey J. Teuteberg, Joseph G. Rogers, JoAnn Lindenfeld, Stephen H. Bailey, Colleen K. McIlvennan, Raymond Benza, Srinivas Murali, James Antaki
Journal: JACC Heart Failure (2018)