tbuckley/cabot-search huggingface dataset:
Abstract P222: Moderate Alcohol Consumption is Associated With a Lower Risk of Coronary Artery Disease: The Million Veteran Program
Authors: Rebecca J Song, Xuan-Mai T Nguyen, Rachel M Quaden, Yuk-Lam Ho, Amy C Justice, Kelly Cho, Christopher J O’Donnell, John Concato, J. Michael Gaziano, Luc Djousse on behalf of the MVP investigators
Journal: Circulation (2017)

Introduction: Moderate alcohol consumption has been shown to protect against coronary artery disease (CAD) in the general population, but this relationship has not been well studied among U.S. Veterans. Methods: 61,587 Million Veteran Program (MVP) participants completed a baseline and lifestyle survey that included questions about frequency and volume of alcohol consumption. We combined grams of ethanol in wine, beer, and spirits to create the exposure variable for this analysis. Using the VA electronical health record, incident CAD events included myocardial infarction, angina pectoris, other forms of chronic ischemic heart disease (ICD9 codes 410-414.9) or coronary procedures (ICD9 procedure codes 36.0-36.99). Participants with prevalent CAD (n=27,844) before the baseline survey date or alcohol abuse using ICD9 codes 303.0 and 305.0 (n=16,048) were excluded from the analysis. We used a Cox Proportional Hazard model to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CAD adjusting for age, sex, body mass index, and smoking status. Results: Among 59,288 participants analyzed, the mean age was 65y (SD=11.9), mean BMI was 28.9 kg/m 2 , 90% were men, 33% were never smokers, 86% self-reported as White, 11% Black, and 6% Hispanic. Participants were categorized into 6 alcohol consumption categories: Never, former, and current drinkers of half drink/d, &gt;half to 1 drink/d, &gt;1 to 2 drinks/d, &gt;2 to 3 drinks/d, &gt;3 to 4 drinks/d, and &gt;4 drinks/d. During a mean follow up of 3.3 years, 3,670 CAD events were documented. Using current drinkers of ≤half a drink/d as the reference group, we found a 19% lower risk of CAD in drinkers of &gt;1 to 2 drinks/d, a 25% lower risk of CAD with alcohol intake of &gt;3 to 4 drinks/d, and 34% lower risk in the highest alcohol category in a multivariable adjusted model (Table 1). As expected, former drinkers had a slightly higher risk of CAD. We did not have enough data on women to conduct sex-specific analyses. Conclusion: Our data show a lower risk of CAD with moderate alcohol consumption among MVP participants.
TCTAP A-061 Percutaneous Closure of Perimembranous Ventricular Septal Defects Using Patent Ductus Arteriosus Closure Device: 5-year Follow-Up Prospective Cohort Study
Authors: Hieu Lan Nguyen, Quang Phan Tan, Hieu Ba Tran, Linh Huynh Dinh, Julian Johny Thottian, Hoyoun Won, SangWook Kim
Journal: Journal of the American College of Cardiology (2018)
Mannose and Mannose‐6‐Phosphate Receptor–Targeted Drug Delivery Systems and Their Application in Cancer Therapy
Authors: Elena Dalle Vedove, Gabriella Costabile, Olivia M. Merkel
Journal: Advanced Healthcare Materials (2018)

In order to overcome the main disadvantages of conventional cancer therapies, which prove to be inadequate because of their lack of selectivity, the development of targeted delivery systems is one of the main focuses in anticancer research. It is repeatedly shown that decorating the surface of nanocarriers with high-affinity targeting ligands, such as peptides or small molecules, is an effective way to selectively deliver therapeutics by enhancing their specific cellular uptake via the binding between a specific receptor and the nanosystems. Nowadays, the need of finding new potential biological targets with a high endocytic efficiency as well as a low tendency to mutate is urgent and, in this context, mannose and mannose-6-phosphate receptors appear promising to target anticancer drugs to cells where their expression is upregulated. Moreover, they open the path to encouraging applications in immune-based and gene therapies as well as in theragnostic purposes. In this work, the potential of mannose- and mannose-6-phosphate-targeted delivery systems in cancer therapy is discussed, emphasizing their broad application both in direct treatments against cancer cells with conventional chemotherapeutics or by gene therapy and also their encouraging capabilities in immunotherapy and diagnostics purposes.
Frialty is an independent predictive factor of hospital admissions and falls in patients with cirrhosis
Authors: E. Roman, M. Parramon, M. Flavià, C. Gely, M. Poca, R. Santesmases, E. Hernández, J.C. Nieto, E. Urgell, E. Alvarado, S. Vidal, V.M.V. Blasco, C. Guarner, G. Soriano
Journal: Journal of Hepatology (2018)
A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and GEJ cancer
Authors: B. F. El-Rayes, B. Patel, M. Zalupski, N. Hammad, A. Shields, L. Heilbrun, R. Venkatramanamoorthy, P. Philip
Journal: Journal of Clinical Oncology (2009)

4563 Background: VEGF (vascular endothelial growth factor) has a central role in angiogenesis, tumor growth and metastasis of gastric cancer. Bevacizumab, an anti-VEGF monoclonal antibody, has demonstrated anti-tumor activity in multiple diseases. This phase II study was undertaken to determine the effects of adding bevacizumab to a regimen of docetaxel and oxaliplatin. Methods: The primary endpoint was time to progression (TTP) in patients with locally advanced or metastatic adenocarcinoma of the gastric or gastroesophageal junction treated with docetaxel, oxaliplatin and bevacizumab. Previously untreated patients with a performance status (PS) of 0–1 were eligible for this study. Patients received bevacizumab 7.5 mg/kg, docetaxel 70 mg/m 2 and oxaliplatin 75 mg/m 2 administered on day 1 of a 21 day cycle. Results: A total of 23 patients (median age 57, males 70%, gastric 52%) were enrolled on the study. Median PS was 1. The median number of cycles was 5. Ten patients are still receiving treatment on study. Partial responses were documented in 10 (59%) patients and stable disease in 7 (41%). No treatment related deaths were observed. The most commonly reported grade 3–4 toxicities were neutropenia (13%), leukopenia (4%), fever (4%), acute neuropathy (4%), and hypertension (4%). Gastrointestinal (GI) perforation occurred in 3 patients. Perforation was not found at the tumor site in the patient who required surgery. The site of perforation could not be ascertained in the second patient who was managed medically. Both patients had had no prior surgical resection of the primary tumor. The third perforation presented as a tracho-bronchial fistula. The patient had previously undergone surgical resection of his primary tumor after receiving chemoradiotherapy to the thoracic area. Conclusions: The regimen of docetaxel, oxaliplatin and bevacizumab appears to be very active. The development of GI perforations in 3 patients is of concern. At this time, bevacizumab should not be used in gastric or gastroesophageal junction cancers outside of a clinical trial until its safety is well established. [Table: see text]
Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster
Authors: Ola Landgren, Rachel Zeig-Owens, Orsolya Giricz, David Goldfarb, Kaznouri Murata, Katie Thoren, Lakshmi Ramanathan, Malin Hultcrantz, Ahmet Dogan, George Nwankwo, Ulrich Steidl, Kith Pradhan, Charles B. Hall, Hillel W. Cohen, Nadia Jaber, Theresa Schwartz, Laura Crowley, Michael Crane, Shani Irby, Mayris P. Webber, Amit Verma, David J. Prezant
Journal: JAMA Oncology (2018)

The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood.To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS.Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781).WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002.Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS.Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93).Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.
Platelet-camouflaged nanococktail: Simultaneous inhibition of drug-resistant tumor growth and metastasis via a cancer cells and tumor vasculature dual-targeting strategy
Authors: Lijia Jing, Haijing Qu, Dongqi Wu, Chaojian Zhu, Yongbo Yang, Xing Jin, Jian Zheng, Xiangsheng Shi, Xiufeng Yan, Yang Wang
Journal: Theranostics (2018)

Multidrug resistance (MDR) poses a great challenge to cancer therapy. It is difficult to inhibit the growth of MDR cancer due to its chemoresistance. Furthermore, MDR cancers are more likely to metastasize, causing a high mortality among cancer patients. In this study, a nanomedicine RGD-NPVs@MNPs/DOX was developed by encapsulating melanin nanoparticles (MNPs) and doxorubicin (DOX) inside RGD peptide (c(RGDyC))-modified nanoscale platelet vesicles (RGD-NPVs) to efficiently inhibit the growth and metastasis of drug-resistant tumors via a cancer cells and tumor vasculature dual-targeting strategy. Methods: The in vitro immune evasion potential and the targeting performance of RGD-NPVs@MNPs/DOX were examined using RAW264.7, HUVECs, MDA-MB-231 and MDA-MB-231/ADR cells lines. We also evaluated the pharmacokinetic behavior and the in vivo therapeutic performance of RGD-NPVs@MNPs/DOX using a MDA-MB-231/ADR tumor-bearing nude mouse model. Results: By taking advantage of the self-recognizing property of the platelet membrane and the conjugated RGD peptides, RGD-NPVs@MNPs/DOX was found to evade immune clearance and target the αvβ3 integrin on tumor vasculature and resistant breast tumor cells. Under irradiation with a NIR laser, RGD-NPVs@MNPs/DOX produced a multipronged effect, including reversal of cancer MDR, efficient killing of resistant cells by chemo-photothermal therapy, elimination of tumor vasculature for blocking metastasis, and long-lasting inhibition of the expressions of VEGF, MMP2 and MMP9 within the tumor. Conclusion: This versatile nanomedicine of RGD-NPVs@MNPs/DOX integrating unique biomimetic properties, excellent targeting performance, and comprehensive therapeutic strategies in one formulation might bring opportunities to MDR cancer therapy.
Single-cell sequencing reveals the origin and the order of mutation acquisition in T-cell acute lymphoblastic leukemia
Authors: Jolien De Bie, Sofie Demeyer, Llucia Alberti-Servera, Ellen Geerdens, Heidi Segers, Michaël Broux, Kim De Keersmaecker, Lucienne Michaux, Peter Vandenberghe, Thierry Voet, Nancy Boeckx, Anne Uyttebroeck, Jan Cools
Journal: Leukemia (2018)

Next-generation sequencing has provided a detailed overview of the various genomic lesions implicated in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). Typically, 10–20 protein-altering lesions are found in T-ALL cells at diagnosis. However, it is currently unclear in which order these mutations are acquired and in which progenitor cells this is initiated. To address these questions, we used targeted single-cell sequencing of total bone marrow cells and CD34+CD38− multipotent progenitor cells for four T-ALL cases. Hierarchical clustering detected a dominant leukemia cluster at diagnosis, accompanied by a few smaller clusters harboring only a fraction of the mutations. We developed a graph-based algorithm to determine the order of mutation acquisition. Two of the four patients had an early event in a known oncogene (MED12, STAT5B) among various pre-leukemic events. Intermediate events included loss of 9p21 (CDKN2A/B) and acquisition of fusion genes, while NOTCH1 mutations were typically late events. Analysis of CD34+CD38− cells and myeloid progenitors revealed that in half of the cases somatic mutations were detectable in multipotent progenitor cells. We demonstrate that targeted single-cell sequencing can elucidate the order of mutation acquisition in T-ALL and that T-ALL development can start in a multipotent progenitor cell.
P152The Q222R deoxyribonuclease I single nucleotide polymorphism is associated with mortality in patients after ST-elevation myocardial infarction
Authors: A Ondracek, T M Hofbauer, T Scherz, J Mueller, A Panzenboeck, A Mangold, I M Lang
Journal: Cardiovascular Research (2018)

recognised: Signal 1 or priming (expression of NLRP3 protein, pro-IL-1b, pro-IL-18 and pro-Caspase-1), followed by Signal 2 or activation (active IL-1b and IL-18).Additionally, Caspase 5 may be involved via a non-canonical pathway.The purpose of this study was to investigate the possible role of mitochondrial and cytosolic superoxide in activating the NLRP3 inflammasome in THP-1 and HUVEC and EA.hy926 endothelial cells.THP-1 cells were differentiated with PMA (5ng/ml) for 1-3 days.Subsequently, LPS treatment (0.1mg/ml) was administered for 24 h for Signal 1 activation followed by ATP (500uM) for 1 hour for Signal 2. The effects of intracellular generation of superoxide (mitoparaquat and paraquat at 1 and 5mM) was investigated before and after LPS.NLRP3, pro-IL-1b, pro-IL-18, pro-Caspase-1 and -5 were detected in THP-1 cell lysates by Western blotting and active IL-1b and IL-18 detected in cell culture supernatants by ELISA.In our hands, intracellular superoxide generation did not activate the NLRP3 inflammasome in PMA-differentiated THP-1 cells nor did it inhibit LPS-induced priming.Both endothelial cell types showed evidence of low level Signal 1 activation.Despite HUVEC cells showing priming of the NLRP3 inflammasome, there was no evidence for either active IL-1b or active IL-18 synthesis.Surprisingly, EA.hy926 cells showed low levels of active IL-1b, when exposed to PMA, suggesting other endpoints of an active NLRP3 inflammasome are worthy of investigation. P151Epicardial placement of mesenchymal stem cells-loaded hydrogel for cardiac repair
Abstract 19781: Life-threatening Arrhythmia in Cardiac Sarcoidosis: Does Left Ventricular Ejection Fraction Matter?
Authors: David G Rosenthal, Richard K Cheng, Bradley J Petek, Daniel M Arnett, Logan Vincent, Paco E Bravo, Ganesh Raghu, Carolina S Masri, Zachary D Goldberger, Kristen K Patton
Journal: Circulation (2017)

Introduction:  Cardiac sarcoidosis (CS) patients with systolic dysfunction experience high rates of ventricular arrhythmias (VA) and sudden cardiac arrest (SCA). However, the risk of VA and SCA in CS patients without significant systolic dysfunction remains incompletely understood.   Methods:  We consecutively identified patients with clinical CS diagnosed per HRS guidelines or suspected isolated CS based on cardiac MRI findings and PET inflammation studies at a tertiary care referral center. Patients were divided into a priori defined groups of biplane LVEF ≥ 40% and LVEF    Results:  Of 110 CS patients, LVEF    Conclusion:  Compared to lower optimal LVEF cutoffs in ischemic and non-ischemic cardiomyopathies, the elevated risk of VA or SCA in CS patients with LVEF ≥ 40% in CS highlights the additional consideration beyond LVEF required to make decisions regarding arrhythmia prevention in this population.
Novel agents for pancreatic ductal adenocarcinoma: emerging therapeutics and future directions
Authors: Yiyin Zhang, Chao Yang, He Cheng, Zhiyao Fan, Qiuyi Huang, Yu Lu, Kun Fan, Guopei Luo, Kaizhou Jin, Zhengshi Wang, Chen Liu, Xianjun Yu
Journal: Journal of Hematology & Oncology (2018)

A poor prognosis of pancreatic ductal adenocarcinoma (PDAC) associated with chemoresistance has not changed for the past three decades. A multidisciplinary diagnosis followed by surgery and chemo(radiation)therapy is the main treatment approach. However, gemcitabine- and 5-fluorouracil-based therapies did not present satisfying outcomes. Novel regimens targeting pancreatic cancer cells, the tumor microenvironment, and immunosuppression are emerging. Biomarkers concerning the treatment outcome and patient selection are being discovered in preclinical or clinical studies. Combination therapies of classic chemotherapeutic drugs and novel agents or novel therapeutic combinations might bring hope to the dismal prognosis for PDAC patients.
P568Old dogma, new aspects - Role of angiotensin converting enzymes in the cardiovascular continuum
Authors: V Banhegyi, M Fagyas, I Manyine Siket, A Enyedi, K Bottyan, I Edes, Z Papp, A Toth
Journal: Cardiovascular Research (2018)

phosphorylation on the inhibitory Ser377 in response to inflammatory stimuli.Endothelial cell-specific CSE deletion reduced H2S bioavailability by 70%, increased 5-fold L-cystathionine circulating levels and resulted in endothelial cell dysfunction in murine aortas, elevated monocyte adhesion and accelerated atherosclerosis.Overall, reduced H2S bioavailability in the murine and human vascular wall resulted in the loss of sulfhydration of the RNA binding protein HuR, which potentiated the homodimerization of HuR and its capacity to bind to the 3' UTR of its targets CD62E and CTSS.Conclusion: H2S produced by CSE, constitutively S-sulfhydrates HuR to inhibit its activity and limit the expression of its pro-atherogenic protein targets.L-cystathionine may serve as a biomarker of endothelial cell dysfunction and a prognostic marker of CSE activity and atherosclerosis development. P565Vascular endothelial cells exposed to oxidized HDL increases LOX-1 destination at the plasma membrane through a mechanism involving ROS/NOX/NF-kB/LOX-1 pathway
Loss of STAG2 expression and prognosis in Ewing sarcoma family of tumors.
Authors: Armita Bahrami, Jianrong Wu, Michael A. Dyer, Olivier Delattre, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2015)

10024 Background: The Ewing sarcoma family of tumors (ESFTs) is an aggressive primitive sarcoma of bone and soft tissue. Although several clinical factors are associated with patient outcomes, few biomarkers have prognostic relevance. Recurrent inactivating mutations or deletions in the cohesin complex subunit STAG2 have been recently described in 15-20% of ESFTs, but their prognostic significance is uncertain. We previously reported that concurrent STAG2 and TP53 mutations in ESFTs predict clinical aggressiveness. In this study of an independent cohort, we evaluated the prognostic significance of STAG2 deficiency on clinical outcomes in correlation with established clinical risk markers. Methods: Immunohistochemical (IHC) analysis for STAG2 was performed on 143 ESFT samples from 111 patients (90 osseous; 21 extraosseous). The Cox regression model was used to study the association between overall survival (OS) and potential risk factors [age at diagnosis ( < 15 vs. ≥ 15 years), gender, primary tumor site (axial vs. extremities), metastatic disease at diagnosis, and STAG2 status]. p53 IHC was performed on STAG2-deficient ESFTs to determine the frequency of coexisting TP53 missense mutations (TP53mut). Results: ESFTs occurred in 68 (66%) male and 43 (34%) female patients with a median age of 12.9 years (range, 5 months to 22 years). Tumors involved extremities in 47 (42%) patients and axial/pelvis in 64 (58%) patients. Metastatic disease at diagnosis was seen in 27 (24%) patients. Of the 111 patients, 38 were alive (median follow-up, 16.1 years), 64 died of disease, and 9 died of other causes (median time to death, 2.8 years). STAG2 was expressed in 95 (86%) tumors and not in 16 (14%) tumors. Of the 16 STAG2-negative tumors, 4(25%) harbored concurrent TP53mut. Cox regression analysis identified metastatic disease at diagnosis as the most significant adverse prognostic indicator for OS (P= 0.0005). Axial location and STAG2 deficiency were associated with a lower OS, but neither reached statistical significance (P= 0.053 and P= 0.059, respectively). Conclusions: Our findings do not support using STAG2 loss as single predictor of outcome. The effects of STAG2 deficiency in ESFTs may be mediated by coexisting genetic modifiers such as TP53 alterations.
Whole genome viral sequencing reveals subgenotype specific dynamics of antiviral treatment response in HBeAg positive and treatment naive chronic hepatitis B patients
Authors: O. Podlaha, K. Agarwal, A. Thompson, G. Foster, D. Samuel, H. Yatsuhashi, A. Gaggar, K. Kitrinos, Z. Jiang, M. Tong, E. Gane, M. Brunetto
Journal: Journal of Hepatology (2018)