tbuckley/cabot-search huggingface dataset:
Abstract 13661: Prediction of Incident Heart Failure With Data From Electronic Medical Records in a Community Hospital
Authors: Weijia Wang, Jingsha Chen, Shoshana Ballew, Josef Coresh, Allen Twigg, Kunihiro Matsushita
Journal: Circulation (2017)

Background: Electronic medical records (EMR) are ubiquitously used, and their data reflect institution-specific patient characteristics and practice patterns. Few attempts have been made to build prediction models for heart failure (HF) using EMR data. Hypothesis: Institution-specific prediction models for incident HF with a number of predictors in EMR data will have excellent discrimination and calibration and be valid over time in that institution. Methods: We used EMR data from Meritus Health, a community hospital in Washington County, Maryland. We set January 1, 2006 as baseline and explored 75 demographic, vital, diagnostic, and lab variables. Based on statistical significance, we developed a prediction model for 5-year risk of incident HF (an admission or two outpatient visits with ICD codes for HF [e.g., 428]). Then, using patient data with January 1, 2010 as baseline, we tried to validate the developed prediction model. Results: In 2006, 144,371 patients (age: 47±17 years, predominantly whites) wi...
Relative Pancreas Volume Is Reduced in First-Degree Relatives of Patients With Type 1 Diabetes
Authors: Martha L. Campbell-Thompson, Stephanie L. Filipp, Joseph R. Grajo, Bimota Nambam, Richard Beegle, Erik H. Middlebrooks, Matthew J. Gurka, Mark A. Atkinson, Desmond A. Schatz, Michael J. Haller
Journal: Diabetes Care (2018)

Pancreas size is reduced in patients at type 1 diabetes onset and in autoantibody (AAB)-positive donors without diabetes. We sought to determine whether pancreas volume (PV) imaging could improve understanding of the loss of pancreas size in first-degree relatives (FDRs) of patients with type 1 diabetes. We also examined relationships among PV, AAB status, and endocrine and exocrine functions.We conducted a cross-sectional study that included five groups: AAB- control subjects (no diabetes and no first- or second-degree relatives with type 1 diabetes) (N = 49), AAB- FDRs (N = 61), AAB+ FDRs (N = 67 total: n = 31 with a single positive AAB [AAB+ single] and n = 36 with multiple positive AABs [AAB+ multiple]), and patients with recent-onset type 1 diabetes (<1 year) (N = 52). Fasting subjects underwent 1.5T pancreatic MRI, and PV and relative PV (RPV) (PV-to-BMI ratio) were analyzed between groups and for correlations with HbA1c, C-peptide, glucose, and trypsinogen.All FDR groups had significantly lower RPV adjusted for BMI (RPVBMI) than control subjects (all P < 0.05). Patients with type 1 diabetes had lower RPVBMI than AAB- FDR (P < 0.0001) and AAB+ multiple (P ≤ 0.013) subjects. Transformed data indicated that trypsinogen levels were lowest in patients with type 1 diabetes.This study demonstrates, for the first time, all FDRs having significantly smaller RPVBMI compared with AAB- control subjects. Furthermore, RPVBMI was significantly lower in patients with recent-onset type 1 diabetes than in the AAB- FDR and AAB+ multiple groups. As such, RPVBMI may be a novel noninvasive biomarker for predicting progression through stages of type 1 diabetes risk. This study highlights the potential paracrine relationships between the exocrine and endocrine pancreas in progression to type 1 diabetes in subjects at risk.
ZD6474, a small molecule targeting VEGF and EGF receptor signaling, inhibits lung angiogenesis and metastasis and improves survival in an orthotopic model of non-small cell lung cancer
Authors: Wenjuan Wu, Takeshi Isobe, Satoshi Itasaka, Tomoaki Shintani, Robert R. Langley, Amir Onn, Jill C. Hansen, Michael S. O’Reilly, Roy S. Herbst
Journal: Cancer Research (2004)

4551  Vascular endothelial and epidermal growth factor receptors (VEGFR, EGFR) are critical regulators of tumor and endothelial cells. To further understand the role of VEGFR and EGFR signaling in human lung cancer progression, we investigated the antiangiogenic and antimetastatic activity of ZD6474 (a selective small molecule inhibitor of VEGFR-2 tyrosine kinase with additional activity against the EGFR tyrosine kinase) using invitro and invivo systems. In the human lung cancer cell line NCI-H441 (which we determined to express VEGF, TGF-alpha, VEGFR-2 and EGFR) and mouse lung endothelial cells (MLECs), ZD6474 inhibited EGFR phosphorylation, VEGFR-2 phosphorylation and subsequently downstream Akt phosphorylation. ZD6474 treatment of both NCI-H441 and MLECs decreased proliferation and colony formation, induced apoptosis and inhibited migration and invasion. These in vitro data suggest that ZD6474 targets multiple events that are important for both angiogenesis and metastasis. ZD6474 also inhibited in vivo angiogenesis formation, demonstrated by a decrease in microvessel density (MVD) in subcutaneously implanted gelfoam–agarose sponges. To better characterize the effect of ZD6474 in human lung cancer, an orthotopic model using NCI-H441 cells was developed that closely mimics the patterns of growth and metastasis observed in the clinic. Treatment was evaluated at different stages of tumor progression (early, middle and late) with ZD6474 initiated on day 5, 10 or 15 after tumor injection, respectively. ZD6474 (25 mg/kg and 50 mg/kg) impaired pleural effusion formation and pleural invasion at every stage. Daily oral dosing with 25 or 50 mg/kg ZD6474 (initiated on day 5 following tumor inoculation) resulted in the almost complete suppression of the growth, invasion and metastasis of established lung tumors, when compared with controls (P 300% relative to the control (25 days vs 80 days, the time of experiment termination, P
Abstract MP072: Low Vitamin K Status is Prospectively Associated With Greater Left Ventricular Mass
Authors: Hanne van Ballegooijen, Ingeborg A Brouwer, Marjolein Visser, Giel Nijpels, Jacqueline M Dekker, Roger J Rennenberg, Cees Vermeer, Coen D Stehouwer, Joline W Beulens
Journal: Circulation (2017)

Introduction: Vitamin K is a fat soluble vitamin and is required as a co-factor for the carboxylation of several proteins. Matrix gla-protein (MGP) requires vitamin K for its activation and is a potent vascular calcification inhibitor. High concentrations of dephosphorylated uncarboxylated MGP (dp-ucMGP) -a functional marker of vitamin K status- are associated with increased coronary artery calcification and cardiovascular disease, but the underlying mechanism remains unclear. Hypothesis: We hypothesized that higher levels of dp-ucMGP (indicating low vitamin K status) are associated with unfavorable measures of cardiac structure and function after 7 years of follow-up. Methods: In the Hoorn Study, a population-based cohort, 598 participants mean age 70.1±6.6 years, 51% female, had physical examinations in 2000-2001 (baseline for the current analyses), of whom 249 had a follow-up in 2007-2009. Plasma dp-ucMGP levels were measured with ELISA in baseline samples. We studied the cross-sectional and prospective association of dp-ucMGP with echocardiographic measures of left ventricular mass index (LVMI), ejection fraction and left atrium volume index using linear regression analyses, adjusted for age, sex, BMI, education, smoking, type 2 diabetes and LDL-cholesterol. Results: Median plasma dp-ucMGP was 567 (392-701) pmol/l and mean follow-up time was 7.0±0.7 year. Cross-sectionally, the highest dp-ucMGP quartile ≥701 pmol/l compared to the lowest quartile &lt;392 pmol/l was associated with a 2.7 g/m 2.7 (95% CI -0.8, 6.2) greater LVMI. In the prospective analysis adjusting for baseline LVMI and follow-up time, the association was more pronounced and became significant 6.5 g/m 2.7 (95% CI 1.5, 11.4). This result was confirmed by the continuous association (Figure 1). No significant associations were observed between dp-ucMGP with ejection fraction and left atrium volume index. Conclusion: In conclusion, these results suggest that a low vitamin K status is prospectively associated with a greater LVMI.
Abstract 9565: Impact of Hepatic GPAT1 or DGAT2 Deficiency on Plasma Lipids and MTP Inhibitor-Induced Elevation of Liver Triglycerides in Mice
Authors: Caroline Houde, Kenny K Wong, Sheng-Ping Wang, David G McLaren, Vivienne Mendoza, Ray Rosa, Paul L Miller, Steven J Stout, Shuo Quan, Aiwu Zhang, Andy Taggart, Thomas P Roddy, Stephen Previs, Heather H Zhou, Doug Johns, Brian K Hubbard
Journal: Circulation (2011)

Purpose: Systemic microsomal triglyceride transfer protein (MTP) inhibitors induce beneficial changes in the serum lipid profile in animals and humans, including reduced total and LDL cholesterol (LDL-C) as well as VLDL triglyceride (TG). However, as a consequence of their mechanism of action, these agents also elevate intestinal and hepatic triglyceride levels. A treatment that ameliorates liver TG accumulation could conceivably prevent hepatotoxicity and provide a path forward for developing these compounds. As a proof of principle, we sought to induce hepatic deficiency of either of two key enzymes in the TG biosynthetic pathway - GPAT1 and DGAT2 - and measure the impact of their loss on liver TG accumulation induced by a MTP inhibitor in mice. Methods: A recombinant adeno-associated viral vector (AAV) was used to introduce shRNA directed against either GPAT1 or DGAT2 to the livers of B6[Tg(CETP)/LDLR tm1 ] F1 mice - a model with a serum lipid profile similar to humans. Stable isotope tracer techniques were employed to assess the degree to which de novo liver TG synthesis was compromised in these animals, thereby indicating in vivo target engagement. Once target engagement was confirmed, the animals were challenged with a MTP inhibitor and liver TG levels assessed ex vivo one week later. Impacts on the plasma lipid profile were also assessed. Results: At 42 days post AAV treatment, hepatic GPAT1 and DGAT2 mRNA levels were reduced by over 90% relative to controls by their respective AAV-shRNA vectors. Both treatments were associated with significant and distinct changes in the manner in which intravenously administered 13 C-oleic acid tracer was incorporated into various lipid species by the liver. Of the two treatments, only DGAT2 altered the overall plasma lipid profile, with significantly reduced plasma TG, Apolipoprotein B, and total, VLDL, LDL and HDL cholesterol. Both treatments significantly lowered liver TG levels, both alone and in response to a MTP inhibitor. In the case of DGAT2, the elevated liver TG induced by MTP inhibition was nearly abolished. Conclusion: These data provide proof of principle that inhibiting hepatic TG synthesis ameliorates liver TG accumulation in response to MTP inhibition.
Adolescent Vaping and Nicotine Use in 2017–2018 — U.S. National Estimates
Authors: Richard Miech, Lloyd Johnston, Patrick M O'Malley, Jerald G Bachman, Megan E Patrick
Journal: New England Journal of Medicine (2018)

To the Editor: Geserick et al. (Oct.4 issue) 1 report tracking body-mass index (BMI) in individual children over time.However, they did not use longitudinal analytic strategies.
Evaluating reinforcement learning agents for anatomical landmark detection
Authors: Amir Alansary, Ozan Oktay, Yuanwei Li, Loic Le Folgoc, Benjamin Hou, Ghislain Vaillant, Konstantinos Kamnitsas, Athanasios Vlontzos, Ben Glocker, Bernhard Kainz, Daniel Rueckert
Journal: Medical Image Analysis (2019)
Abstract 18323: Electrocardiographic Changes as a Predictor of Right Ventricle Dysfunction in Acute Pulmonary Embolism
Authors: Ana Devesa, Ana Lucía Rivero, Angelica María Romero-Daza, Juan Martínez-Milla, Marcelino Cortés, Miguel Ángel Navas, Jerónimo Farré
Journal: Circulation (2017)

Background: Acute pulmonary embolism (APE) is a common potentially life-threatening condition. Right ventricular (RV) dysfunction is associated with poor prognosis in patients with APE. However, there is lack of information regarding electrocardiographic (ECG) changes and its relationship with APE prognosis. The aim of this study is to describe the ECG changes in APE and evaluate their relationship with RV dysfunction as an indicator of poor prognosis. Methods: From January 2010 to February 2017 all patients admitted in our coronary care unit (CCU) with APE were included. A multivariate logistic regression analysis was made to evaluate the relationship between ECG changes and RV dysfunction parameters in transthoracic echocardiogram (TTE). Results: 226 patients were included, 57.1% were female, mean age was 74.5 years (IR: 61- 81). At admission ECG and TTE were performed in all patients. The most frequent ECG findings at admission were Negative T waves, S1Q3T3 pattern and sinus tachycardia, in a 49%, 44% ...
Clear cell acanthoma (CCA)-like lesions of the nipple/areola: A clinicopathological study of 12 cases supporting a nonneoplastic eczematous disease
Authors: Kang-Ling Kuo, Chi-Shou Lo, Li-yu Lee, Chih-Hsun Yang, Tseng-tong Kuo
Journal: Journal of the American Academy of Dermatology (2018)
Abstract 14538: MANP: A Novel Aldosterone Inhibitor: Potential Molecular Mechanisms in vitro in Human Adrenal Cells
Authors: Yang Chen, Seethalakshmi Iyer, John Burnett
Journal: Circulation (2017)

Introduction: Aldosterone (Aldo) is synthesized and secreted by the adrenal cortex zona glomerulosa (ZG) cells. In cardiovascular (CV) disease Aldo is increased and plays a critical role in disease...
Novel TLR2-binding adjuvant induces enhanced T cell responses and tumor eradication
Authors: Gijs G. Zom, Marian M. J. H. P. Willems, Selina Khan, Tetje C. van der Sluis, Jan Willem Kleinovink, Marcel G. M. Camps, Gijsbert A. van der Marel, Dmitri V. Filippov, Cornelis J. M. Melief, Ferry Ossendorp
Journal: Journal for ImmunoTherapy of Cancer (2018)

Ligands for the Toll-like receptor (TLR) family can induce activation of cells of the innate immune system and are widely studied for their potential to enhance adaptive immunity. Conjugation of TLR2-ligand Pam3CSK4 to synthetic long peptides (SLPs) was shown to strongly enhance the induction of antitumor immunity. To further improve cancer vaccination, we have previously shown that the novel TLR2-L Amplivant (AV), a modified Pam3CSK4, potentiates the maturation effects on murine DCs. In the current study, we further assessed the immunological properties of AV.Naïve mice were vaccinated with a conjugate of either Pam3CSK4 or AV and an SLP to assess specific T cell priming efficiency in vivo. The potency of AV and Pam3CSK4, either as free compounds or conjugated to different SLPs, to mature murine DCs was compared by stimulating murine dendritic cells overnight followed by ELISA and flow cytometry analysis. Murine tumor experiments were carried out by vaccinating mice carrying established HPV16 E6 and E7-expressing tumors and subsequently analyzing myeloid and lymphoid cells infiltrating the tumor microenvironment. Furthermore, tumor outgrowth after vaccination was monitored to enable comparison of the efficiency to induce antitumor immunity by Pam3CSK-SLP and AV-SLP conjugates. To enhance therapeutic efficacy, AV-SLP conjugate vaccination was combined with ablative therapies to assess whether synergism between such therapies would occur.SLPs conjugated to AV induce stronger DC maturation, in vivo T cell priming and antitumor immunity compared to conjugates with Pam3CSK4. Interestingly, AV-SLP conjugates modulate the macrophage populations in the tumor microenvironment, correlating with a therapeutic effect in an aggressive murine tumor model. The potency of AV-SLP conjugates in cancer vaccination operates optimally in combination with chemotherapy or photodynamic therapy.These data allow further optimization of vaccination-based immunotherapy of cancer by use of the improved TLR2-ligand Amplivant.
HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis
Authors: Nick Dand, Michael Duckworth, David Baudry, Alice Russell, Charles J. Curtis, Sang Hyuck Lee, Ian Evans, Kayleigh J. Mason, Ali Alsharqi, Gabrielle Becher, A. David Burden, Richard G. Goodwin, Kevin McKenna, Ruth Murphy, Gayathri K. Perera, Radu Rotarescu, Shyamal Wahie, Andrew Wright, Nick J. Reynolds, Richard B. Warren, Christopher E.M. Griffiths, Catherine H. Smith, Michael A. Simpson, Jonathan N. Barker, Marilyn Benham, Sagair Hussain, Brian Kirby, Linda Lawson, Kathleen McElhone, Anthony Ormerod, Caroline Owen, Michael R. Barnes, Paola Di Meglio, Richard Emsley, Andrea Evans, Katherine Payne, Deborah Stocken
Journal: Journal of Allergy and Clinical Immunology (2018)
Breast implants linked to rare cancer are removed from European market
Authors: Deborah Cohen
Journal: BMJ (2018)

One of the world’s best selling types of silicone breast implants, which have been linked to a rare form of atypical lymphoma (BIA-ALCL), have been removed from the market across Europe.

The recall of Allergan textured implants came after the French national agency for the safety of medicines and health products (ANSM) said it was suspending the Conformite Europeene (CE) mark for Allergan’s Microcell and Biocell products.

It means that, for now, the implants cannot be manufactured or sold in Europe and those held at clinics are being recalled.

French authorities said they had not “identified any immediate risk for the …
Role of Systemic High-Dose Methotrexate and Combined Approaches in the Management of Vitreoretinal Diffuse Large B-Cell Lymphoma: A Single Center Experience 1990-2018
Authors: Alessia Castellino, Jose Pulido, Patrick Johnston, Kay M. Ristow, Nabila Nora Bennani, David J Inwards, William R. Macon, Ivana N Micallef, Rebecca L King, Diva Salomao, Thomas E. Witzig, Thomas M. Habermann, Grzegorz Nowakowski
Journal: Blood (2018)
Specific and Synergistic Targeting of JAK2V617F Cells By Interferon Alpha and Arsenic
Authors: Nabih Maslah1, Tracy Dagher, Valérie Edmond, Bruno Cassinat, Valérie Lallemand-Breitenbach, Emmanuelle Verger, Isabelle Plo, Jean-Jacques Kiladjian, Jean-Luc Villeval, Hugues de Thé
Journal: Blood (2018)
Baseline CRP predicts severe immune related adverse events
Authors: R. Verheijden, K. Suijkerbuijk
Journal: Annals of Oncology (2018)

Background: The PD-1 inhibitors nivolumab and pembrolizumab are currently widely used as treatment of advanced melanoma. While being tolerated very well by some patients, they cause severe and even fatal immune related adverse events (irAEs) in others. Factors associated with increased risk of toxicity have barely been identified. With the perspective of long-term survival in stage IV disease, and increasing numbers of patients receiving adjuvant immunotherapy in stage III melanoma, being able to predict severe (≥grade 3) toxicity becomes more and more important. In this study, we aimed to assess factors associated with severe irAEs in clinical data and routine peripheral blood tests. Methods: Patients with advanced (stage III-IV) melanoma, treated with nivolumab or pembrolizumab with at least 3 months follow-up were included. Demographical parameters together with lactate dehydrogenases (LDH), C-reactive protein (CRP), leukocytes, eosinophils, neutrophils and lymphocytes at baseline and at last measurement before toxicity were retrieved retrospectively. IrAEs were graded according to CTCAE 4.03. Non parametric tests were used to assess the difference between groups. Results: 60 patients treated with anti-PD1 monotherapy were included, of whom 7 developed ≥grade 3 irAEs. Median CRP at baseline was significantly higher in patients that experienced severe irAEs (25mg/L) compared to patients who did not (3 mg/L; p = 0,038). Furthermore, in patients with severe irAEs, median eosinophil level at last measurement before toxicity (0,27x109/L) was significantly increased compared to baseline (0,15x109/L; p = 0,047). Conclusions: Our data indicate that baseline CRP is a potential predictor of severe anti-PD1 induced toxicity. If confirmed in a larger study, CRP could play a role in clinical decision making at the start of treatment. Furthermore, our observation that increase of eosinophils precedes ≥grade 3 toxicity underpins its possible role in the pathogenesis of irAEs and could help identify and treat irAEs at an early stage. Legal entity responsible for the study: University Medical Center Utrecht. Funding: Has not received any funding. Disclosure: K. Suijkerbuijk: Consulting/advisory relationship: Bristol-Myers Squibb, MSD; Honoraria (paid to institution): Novartis, Roche. All other authors have declared no conflicts of interest.
Abstract 11511: Insulin Resistance is an Independent Predictor for Impaired Exercise Tolerance in Hypertensive Patients Without Type 2 Diabetes Mellitus
Authors: Haruka Ishii, Daisuke Kamekawa, Yumi Kamada, Mayu Katagiri, Hitomi Koshi, Takumi Sakai, Ayako Akiyama, Kentaro Kamiya, Ryosuke Shimizu, Minoru Tabata, Chiharu Noda, Takashi Masuda
Journal: Circulation (2012)

Background Increase of insulin resistance is well known to cause the autonomic imbalance and decreased muscle strength, resulting in the impaired exercise tolerance in patients with type 2 diabetes...
Abstract 14618: Cavbeta2a Overexpression in Smooth Muscle Causes Hypertension via Impairment of Acetylcholine-dependent Vascular Relaxation
Authors: Xiaoying Zhang, Zhongjian Cheng, Xiaojie Ai, Mingxin Tang, Xiang Hua, steven R Houser, Manuel F Navedo, Luis F Santana, Hong Wang, Xiongwen Chen
Journal: Circulation (2016)

Introduction: The L-type Calcium channel (Cav1.2) plays an important role in smooth muscle contraction (via providing Ca2+ for contraction and inducing Ca2+ release from the sarcoplasmic reticulum)...
Low-dose chidamide restores immune tolerance in ITP in mice and humans
Authors: Hong-yu Zhao, Ya-hui Ma, Da-qi Li, Tao Sun, Li-zhen Li, Ping Li, Xin-guang Liu, Hai Zhou, Yu Hou, Yang Liu, Pan-pan Han, Ya-jing Zhao, Fang-miao Jing, Jun Peng, Ming Hou
Journal: Blood (2018)
Abstract 18096: Interrelationship Between Reduction in Weight and Adiposity Indices and Improvement in Cardiovascular Death and Heart Failure Outcomes With Empagliflozin in Patients With Type 2 Diabetes in EMPA-REG OUTCOME
Authors: Ian J Neeland, Darren K McGuire, Uwe Hehnke, Hans-Juergen Woerle, David Fitchett, Odd Erik Johansen
Journal: Circulation (2017)

Introduction: In EMPA-REG OUTCOME®, empagliflozin significantly reduced CV death by 38% and hospitalization for heart failure and HF death by 39%. Whether empagliflozin-mediated reduction in weight...
Business not as usual: how multisectoral collaboration can promote transformative change for health and sustainable development
Authors: Shyama Kuruvilla, Rachael Hinton, Ties Boerma, Ryan Bunney, Nuria Casamitjana, Rafael Cortez, Patrizia Fracassi, Jennifer Franz-Vasdeki, Daniel Helldén, Joanne McManus, Susan Papp, Kumanan Rasanathan, Jennifer Requejo, Karlee L Silver, Petra Tenhoope-Bender, Yael Velleman, Mary Nell Wegner, Corinne E Armstrong, Sarah Barnett, Carla Blauvelt, Saidatul Norbaya Buang, Louise Bury, Emily A Callahan, Jai K Das, Vandana Gurnani, Mary White Kaba, Helia Molina Milman, John Murray, Ilona Renner, Marion Leslie Roche, Victoria Saint, Sarah Simpson, Hasina Subedar, Daria Ukhova, Claudia Nieves Velásquez, Patricia Young, Wendy Graham
Journal: BMJ (2018)

<b>Shyama Kuruvilla and colleagues</b> present findings across 12 country case studies of multisectoral collaboration, showing how diverse sectors intentionally shape new ways of collaborating and learning, using "business not as usual" strategies to transform situations and achieve shared goals