tbuckley/cabot-search huggingface dataset:
Abstract 16064: Coronary Artery Calcification, Left Atrial, and Left Ventricular Size Measured From Non-contrast Cardiac CT Predict Incident Heart Failure Hospitalization in the General Population
Authors: Iryna Dykun, Nils Lehmann, Hagen Kälsch, Isabelle Nöllen, Marie Henrike Geisel, Stefan Möhlenkamp, Susanne Moebus, Karl-Heinz Jöckel, Raimund Erbel, Amir Mahabadi
Journal: Circulation (2015)

Objective: Non-contrast cardiac computed tomography (CT) is increasingly performed especially in the absence of known cardiac disease. We aimed to determine, whether CT-derived left atrial (LA), left ventricle (LV) size, and coronary artery calcification (CAC) are associated with future hospitalizations due to heart failure (HF). Methods: Subjects without known cardiac diseases from the population based Heinz Nixdorf Recall Study were followed for incident HF hospitalization. From non-contrast cardiac CT, LA and LV area were measured from axial images and indexed by body surface area. Cox regression analysis determined the association of each CT-measure with HF hospitalization in unadjusted and ASCVD-Score (atherosclerotic cardiovascular disease, pooled cohort risk equation) adjusted analysis. Hazard ratios (HR) and 95% confidence intervals are shown per standard deviation of LA/LV area and increase in log(CAC+1) by 1. Results: From 3944 subjects without known cardiac disease (59±8 years, 47% male, mean ASCVD-Score 11.3±10.8%), 31 subjects (0.8%) were hospitalized due to HF during 10.3±2.0 years of follow-up. LA index, LV index, and CAC-score were significantly associated with incident HF hospitalization in unadjusted analysis (LA: 3.24 [1.75-5.99], p=0.0002, LV: 5.65 [3.02-10.57], p&lt;0.0001, CAC: 1.30 [1.12-1.51], p=0.0007). HRs remained significant for all three CT-measures after adjustment for ASCVD-Score (LA: 2.59 [1.36-4.94], p=0.004; LV: 4.19 [2.17-8.08], p&lt;0.0001, CAC: 1.19 [1.01-1.40], p=0.042). Stratifying by age at baseline, association of LA and LV were stronger for younger subjects (&lt;65 years: LA: 4.26 [1.91-9.49], p=0.0004; LV: 7.38 [3.23-16.88], p&lt;0.0001; ≥65 years: LA: 1.40 [0.57-3.48], p=0.5; LV: 3.08 [1.13-8.36], p=0.03) while CAC-score was stronger in older subjects (&lt;65 years: 1.07 [0.84-1.36], p=0.6; ≥65 years: 1.29 [1.01-1.65], p=0.041) in ASCVD-adjusted analysis. Conclusion: LA size, LV size, and CAC-score as measured from non-contrast cardiac CT are associated with incident HF hospitalization in the general population. Once cardiac CT is performed, quantification of LA and LV size may identify subjects at early and subclinical stages of HF that qualify for further cardiac workup, especially in younger age.
Extracellular Adenosine Stimulates Vacuolar ATPase–Dependent Proton Secretion in Medullary Intercalated Cells
Authors: Maria A. Battistone, Anil V. Nair, Claire R. Barton, Rachel N. Liberman, Maria A. Peralta, Diane E. Capen, Dennis Brown, Sylvie Breton
Journal: Journal of the American Society of Nephrology (2017)

Export Acidosis is an important complication of AKI and CKD. Renal intercalated cells (ICs) express the proton pumping vacuolar H+-ATPase (V-ATPase) and are extensively involved in acid-base homeostasis. H+ secretion in type A intercalated cells (A-ICs) is regulated by apical vesicle recycling and stimulated by cAMP. In other cell types, cAMP is increased by extracellular agonists, including adenosine, through purinergic receptors. Adenosine is a Food and Drug Administration–approved drug, but very little is known about the effect of adenosine on IC function. Therefore, we investigated the role of adenosine in the regulation of V-ATPase in ICs. Intravenous treatment of mice with adenosine or agonists of ADORA2A and ADORA2B purinergic P1 receptors induced V-ATPase apical membrane accumulation in medullary A-ICs but not in cortical A-ICs or other IC subtypes. Both receptors are located in A-IC apical membranes, and adenosine injection increased urine adenosine concentration and decreased urine pH. Cell fractionation showed that adenosine or an ADORA2A or ADORA2B agonist induced V-ATPase translocation from vesicles to the plasma membrane and increased protein kinase A (PKA)–dependent protein phosphorylation in purified medullary ICs that were isolated from mice. Either ADORA2A or ADORA2B antagonists or the PKA inhibitor mPKI blocked these effects. Finally, a fluorescence pH assay showed that adenosine activates V-ATPase in isolated medullary ICs. Our study shows that medullary A-ICs respond to luminal adenosine through ADORA2A and ADORA2B receptors in a cAMP/PKA pathway–dependent mechanism to induce V-ATPase–dependent H+ secretion.
Abstract 28: Identifying mechanisms of PD-L1 regulation in HNSCC
Authors: Jacqueline E. Mann, Megan Ludwig, Aditi Kulkarni, Rebecca Hoesli, Judy Kafelghazal, Alexey Nesvizhskii, J. Chad Brenner
Journal: Clinical Cancer Research (2017)

Abstract Evidence of immunosuppression is frequently reported in head and neck squamous cell carcinoma (HNSCC). Thus, there has been growing interest in advancing therapies for HNSCC that relieving immunosuppression to permit anti-tumor immunity. The immune checkpoint inhibitor Pembrolizumab targets the coinhibitory PD-1/PD-L1 pathway, which serves to shield tumor cells from attack by cytotoxic T lymphocytes. While Pembrolizumab was recently approved for the treatment of metastatic and recurrent HNSCC, the initial trial reported overall response rates of only 18%. A more comprehensive understanding of the intrinsic and extrinsic mechanisms inducing PD-L1 expression on tumor cells may reveal therapeutic targets that improve response to immune modulation. We have employed a high-throughput genetic screen to identify targetable signaling pathways that may regulate PD-L1 expression in patients with specific genetic lesions. The Genome-scale CRISPR Knock-Out (GeCKO) library, established in multiple HNSCC cell lines, consists of a pool of stable knockouts targeting &amp;gt;20,000 genes with representation of approximately 300 gRNAs per target gene. Sub-populations with enhanced or diminished expression of PD-L1 were sequenced to identify gRNA targets whose knockout causes a change in PD-L1 expression. We expect that by performing these screens across multiple cell lines with diverse genetic lesions, pathways consistently regulating PD-L1 expression will be revealed, and that targeting such pathways will provide novel avenues for modulating this immunosuppressive mechanism. Citation Format: Jacqueline E. Mann, Megan Ludwig, Aditi Kulkarni, Rebecca Hoesli, Judy Kafelghazal, Alexey Nesvizhskii, J. Chad Brenner. Identifying mechanisms of PD-L1 regulation in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 28.
Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study
Authors: Raul Martínez-Fernández, Rafael Rodríguez-Rojas, Marta del Álamo, Frida Hernández-Fernández, Jose A Pineda-Pardo, Michele Dileone, Fernando Alonso-Frech, Guglielmo Foffani, Ignacio Obeso, Carmen Gasca-Salas, Esther de Luis-Pastor, Lydia Vela, José A Obeso
Journal: The Lancet Neurology (2017)
Arming oncolytic adenovirus with FAP-targeting bispecific T-cell engager to improve antitumor efficacy
Authors: J. de Sostoa Pomés, C.A. Fajardo, M Farrera Sal, R. Moreno, M. Arias-Badia, L.A. Rojas, R. Alemany
Journal: Annals of Oncology (2017)
Marked elevation of serum lactate dehydrogenase in primary myelofibrosis: clinical and prognostic correlates
Authors: Sahrish Shah, Mythri Mudireddy, Curtis A. Hanson, Rhett P. Ketterling, Naseema Gangat, Animesh Pardanani, Ayalew Tefferi
Journal: Blood Cancer Journal (2017)

Primary myelofibrosis (PMF) is a clonal stem cell-derived myeloproliferative neoplasm (MPN), characterized by dysregulated proliferation of megakaryocytes, myeloid and erythroid cells, extramedullary hematopoiesis, and reactive changes in the bone marrow, including reticulin deposition, osteosclerosis, and neo-angiogenesis 1 .Patients with PMF often experience transfusion-dependent anemia, hepatosplenomegaly, vascular events, infections, cachexia, leukemic transformation, and shortened survival 1, 2 .About 90% of the patients with PMF carry JAK2, CALR, or MPL mutations, which are often mutually exclusive and are referred to as "driver" mutations 1, 3 .Current prognostication in PMF employs the International Prognostic Scoring System (IPSS) 4 , Dynamic IPSS (DIPSS) 5 , and DIPSS-plus 6 .Additional prognostic contribution from driver mutational status and presence or absence of high-risk mutations, such as ASXL1 and SRSF2, has since been realized.Furthermore, the World health Organization (WHO) classification system underscores the prognostically relevant distinction between overt and early/prefibrotic PMF (pre-PMF) 7 .Most recently, we reported leukocytosis-independent contribution of serum lactate dehydrogenase (LDH) in essential thrombocythemia (ET) 8 .In the current study, we looked for a similar possibility in PMF, in the context of conventional risk models.
Is It Our Duty To Hunt for Pathogenic Mutations?
Authors: Roel H.P. Wouters, Rhodé M. Bijlsma, Geert W.J. Frederix, Margreet G.E.M. Ausems, Johannes J.M. van Delden, Emile E. Voest, Annelien L. Bredenoord
Journal: Trends in Molecular Medicine (2017)
Abstract 23242: SOMVC001(DuraGraft) Vascular Graft Treatment in Patients Undergoing Coronary ArteryBypass Grafting
Authors: Louis Perrault
Journal: Circulation (2016)

Background:  The principal mechanism thought to limit the benefits of CABG is saphenous vein graft disease leading to vein graft failure (VGF). Injury to the saphenous vein graft (SVG) endothelium during harvesting and implantation promotes inflammation and neointimal hyperplasia that can lead to subsequent graft atherosclerosis and occlusion. We investigated the impact of a novel intraoperative vein graft treatment SOMVC001 (DuraGraft) on angiographic early graft wall thickness and late lumen loss in patients undergoing CABG.   Methods:  This is a prospective randomized, double-blinded study designed to compare within patient the impact of DuraGraft vs. the standard of care by evaluating the magnitude of change in the mean wall thickness of paired grafts within patients from 4-6 weeks to 3 months and the change from 4-6 weeks to 12 months in mean lumen diameter over each graft plus the lumen diameter at maximal stenosis within-person following CABG surgery using 64-slice or better multi-detector computed tomography (MDCT) angiography.   Results:  Enrollment of 134 patients from seven investigational sites was completed. Patient baseline and procedural characteristics is representative of a contemporary population of individuals undergoing initial CABG with at least two SVG. MDCT angiographic follow-up is ongoing and scheduled to be completed in October 2016.   Conclusions:  The study data will establish whether SVGs pretreated with DuraGraft can prevent early (1 to 3 months) graft wall thickness as an expression of intima hyperplasia and late (12 months) graft lumen loss as an expression of VGF in patients undergoing CABG surgery.
AAV8-antiVEGFfab Ocular Gene Transfer for Neovascular Age-Related Macular Degeneration
Authors: Yuanyuan Liu, Seth D. Fortmann, Jikui Shen, Erik Wielechowski, Anna Tretiakova, Stephen Yoo, Karen Kozarsky, Jiangxia Wang, James M. Wilson, Peter A. Campochiaro
Journal: Molecular Therapy (2017)

Sustained suppression of VEGF is needed in many patients with neovascular age-related macular degeneration (NVAMD), and gene transfer of a VEGF-neutralizing protein is a promising approach to achieve it. Initial clinical trials testing this approach have shown encouraging signals, but evidence of robust transgene expression and consistent antiangiogenic and antipermeability activity has been lacking. In this study, we demonstrate expression of an anti-human VEGF antibody fragment (antiVEGFfab) after subretinal injection of AAV8-antiVEGFfab. In transgenic mice expressing human VEGF in retina (rho/VEGF mice), a model of type 3 choroidal neovascularization (NV), eyes injected with ≥1 × 107 gene copies (GC) of AAV8-antiVEGFfab had significantly less mean area of NV than null vector-injected eyes. A dose-dependent response was observed with modest reduction of NV with ≤3 × 107, >50% reduction with ≥1 × 108 GC and almost complete elimination of NV with 3 × 109 or 1 × 1010 GC. In Tet/opsin/VEGF mice, in which doxycycline-induced high expression of VEGF leads to severe vascular leakage and exudative retinal detachment (RD), reduction of total RD by 70%–80% occurred with 3 × 109 or 1 × 1010 GC of AAV8-antiVEGFfab, an effect that was sustained for at least a month. These data strongly support initiating clinical trials testing subretinal injection of AAV8-antiVEGFfab in patients with NVAMD. Sustained suppression of VEGF is needed in many patients with neovascular age-related macular degeneration (NVAMD), and gene transfer of a VEGF-neutralizing protein is a promising approach to achieve it. Initial clinical trials testing this approach have shown encouraging signals, but evidence of robust transgene expression and consistent antiangiogenic and antipermeability activity has been lacking. In this study, we demonstrate expression of an anti-human VEGF antibody fragment (antiVEGFfab) after subretinal injection of AAV8-antiVEGFfab. In transgenic mice expressing human VEGF in retina (rho/VEGF mice), a model of type 3 choroidal neovascularization (NV), eyes injected with ≥1 × 107 gene copies (GC) of AAV8-antiVEGFfab had significantly less mean area of NV than null vector-injected eyes. A dose-dependent response was observed with modest reduction of NV with ≤3 × 107, >50% reduction with ≥1 × 108 GC and almost complete elimination of NV with 3 × 109 or 1 × 1010 GC. In Tet/opsin/VEGF mice, in which doxycycline-induced high expression of VEGF leads to severe vascular leakage and exudative retinal detachment (RD), reduction of total RD by 70%–80% occurred with 3 × 109 or 1 × 1010 GC of AAV8-antiVEGFfab, an effect that was sustained for at least a month. These data strongly support initiating clinical trials testing subretinal injection of AAV8-antiVEGFfab in patients with NVAMD.
Tolerancia a una gastroscopia dependiendo de la información dada previamente
Authors: C Echeverría Perez, MDP Ortiz Lana, A Esparza Nieva, N Vergara Torres, EL Borobio Aguilar, A Cebrián García, R Irisarri Garde, M Polo Gil
Journal: Endoscopy (2017)

La gastroscopia es una exploración que permite la visualización directa de la parte alta del tubo digestivo (esófago, estómago y duodeno). No es un procedimiento doloroso, pero puede provocar náuseas e incomodidad al paciente. Por eso se puede aplicar anestesia local mediante una pastilla de tetracaina 30 mg que el paciente debe chupar por lo menos 5 minutos previos a la prueba.
Risk Assessment in Patients With Diabetes With the TIMI Risk Score for Atherothrombotic Disease
Authors: Brian A. Bergmark, Deepak L. Bhatt, Eugene Braunwald, David A. Morrow, Ph. Gabriel Steg, Yared Gurmu, Avivit Cahn, Ofri Mosenzon, Itamar Raz, Erin Bohula, Benjamin M. Scirica
Journal: Diabetes Care (2017)

OBJECTIVE Improved risk assessment for patients with type 2 diabetes and elevated cardiovascular (CV) risk is needed. The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P) predicts a gradient of risk in patients with prior myocardial infarction (MI) but has not been evaluated in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS CV event rates were compared by baseline TRS 2°P in 16,488 patients enrolled in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53) with type 2 diabetes and high CV risk or established CV disease. Calibration was tested in the diabetes cohort from the REACH (REduction of Atherothrombosis for Continued Health) Registry. RESULTS TRS 2°P revealed a robust risk gradient for the composite of CV death, MI, and ischemic stroke in the full trial population, with 2-year event rates of 0.9% in the lowest- and 19.8% in the highest-risk groups (Ptrend &amp;lt; 0.001). A clear risk gradient was present within the subgroups of all coronary artery disease (CAD), CAD without prior MI, CAD with prior MI, peripheral artery disease, and prior stroke (Ptrend &amp;lt; 0.001 for each), with consistent risk relationships across subgroups. The C-statistic (0.71 for CV death and 0.66 for the composite end point) was consistent in each subgroup. There was close calibration with the type 2 diabetes cohort from the REACH Registry (goodness-of-fit P = 0.78). CONCLUSIONS The expanded TRS 2°P provides a practical and well-calibrated risk prediction tool for patients with type 2 diabetes.
Deficiency Of Toll-Like Receptor 3 (tlr3) Exacerbates Pulmonary Hypertension In Mice
Authors: Thompson Aar., N D Arnold, A T Braithwaite, H L Casbolt, J A Pickworth, J E Cole, C Monaco, D Kiely, I Sabroe, A Lawrie
Journal: American Journal of Respiratory and Critical Care Medicine (2016)
Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study
Authors: Rajit K Basu, Ahmad Kaddourah, Stuart L Goldstein, Ayse Akcan-Arikan, Megan Arnold, Cody Cruz, Michele Goldsworthy, Nancy Jaimon, Stephen Alexander, Marino Festa, Deirdre Hahn, Lauren Brown, Ari Jeon, Akash Deep, David Askenazi, Sean Bagshaw, Catherine Morgan, Rashid Alobaidi, Rajit Basu, David Cooper, Stuart Goldstein, Ahmad Kaddourah, Theresa Mottes, Tara Terrell, Patricia Arnold, Christina Metcalf, Shalayna Woodley, Radovan Bogdanović, Natasa Stajić, Branko Kovacevic, Amira Peco-Antic, Aleksandra Paripovic, Patrick Brophy, Timothy Bunchman, Duane Williams, Michelle Hoot, Vimal Chadha, Keefe Davis, Vikas Dharnidharka, Leslie Walther, Vincent Faustino, Janet Taft, Joana Tala, Katja Gist, Danielle Soranno, Il Soo Ha, Hee Gyung Kang, Richard Hackbarth, Mary Avendt-Reeber, Chloe Butler, Doug DeGraaf, Dawn Eding, Nathalie Hautala, Akunne Ndika, Eka Laksmi Hidayati, Songming Huang, Sean Kennedy, Madeleine Didsbury, Hari Kushartono, Risky Prasetyo, Cherry Mammen, Matthew Paden, Cheryl Stone, Stefano Picca, Federica Connola, James Schneider, Todd Sweberg, Aaron Kessel, David Selewski, Susan Hieber, Brankica Spasojević-Dimitrijeva, Ivana Ivanisevic, Jovana Putnik, Snezana Ristic, Scott Sutherland, Amy Staples, Craig Wong, Senan Hadid, Catherine Joseph, Robert Woroniecki, Michael Zappitelli, Noha Elsaerafy, Joshua Zaritsky
Journal: The Lancet Child & Adolescent Health (2017)
Association of US State Implementation of Newborn Screening Policies for Critical Congenital Heart Disease With Early Infant Cardiac Deaths
Authors: Rahi Abouk, Scott D. Grosse, Elizabeth C. Ailes, Matthew E. Oster
Journal: JAMA (2017)

In 2011, critical congenital heart disease was added to the US Recommended Uniform Screening Panel for newborns, but whether state implementation of screening policies has been associated with infant death rates is unknown.To assess whether there was an association between implementation of state newborn screening policies for critical congenital heart disease and infant death rates.Observational study with group-level analyses. A difference-in-differences analysis was conducted using the National Center for Health Statistics' period linked birth/infant death data set files for 2007-2013 for 26 546 503 US births through June 30, 2013, aggregated by month and state of birth.State policies were classified as mandatory or nonmandatory (including voluntary policies and mandates that were not yet implemented). As of June 1, 2013, 8 states had implemented mandatory screening policies, 5 states had voluntary screening policies, and 9 states had adopted but not yet implemented mandates.Numbers of early infant deaths (between 24 hours and 6 months of age) coded for critical congenital heart disease or other/unspecified congenital cardiac causes for each state-month birth cohort.Between 2007 and 2013, there were 2734 deaths due to critical congenital heart disease and 3967 deaths due to other/unspecified causes. Critical congenital heart disease death rates in states with mandatory screening policies were 8.0 (95% CI, 5.4-10.6) per 100 000 births (n = 37) in 2007 and 6.4 (95% CI, 2.9-9.9) per 100 000 births (n = 13) in 2013 (for births by the end of July); for other/unspecified cardiac causes, death rates were 11.7 (95% CI, 8.6-14.8) per 100 000 births in 2007 (n = 54) and 10.3 (95% CI, 5.9-14.8) per 100 000 births (n = 21) in 2013. Early infant deaths from critical congenital heart disease through December 31, 2013, decreased by 33.4% (95% CI, 10.6%-50.3%), with an absolute decline of 3.9 (95% CI, 3.6-4.1) deaths per 100 000 births after states implemented mandatory screening compared with prior periods and states without screening policies. Early infant deaths from other/unspecified cardiac causes declined by 21.4% (95% CI, 6.9%-33.7%), with an absolute decline of 3.5 (95% CI, 3.2-3.8) deaths per 100 000 births. No significant decrease was associated with nonmandatory screening policies.Statewide implementation of mandatory policies for newborn screening for critical congenital heart disease was associated with a significant decrease in infant cardiac deaths between 2007 and 2013 compared with states without these policies.
C5a receptor 1 promotes autoimmunity, neutrophil dysfunction and injury in experimental anti-myeloperoxidase glomerulonephritis
Authors: Jonathan Dick, Poh-Yi Gan, Sharon L. Ford, Dragana Odobasic, Maliha A. Alikhan, Sven H. Loosen, Pam Hall, Clare L. Westhorpe, Anqi Li, Joshua D. Ooi, Trent M. Woodruff, Charles R. Mackay, A. Richard Kitching, Michael J. Hickey, Stephen R. Holdsworth
Journal: Kidney International (2017)
Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry
Authors: Sandra Sanchez-Roige, Pierre Fontanillas, Sarah L. Elson, Anita Pandit, Ellen M. Schmidt, Johanna R. Foerster, Gonçalo R. Abecasis, Joshua C. Gray, Harriet de Wit, Lea K. Davis, James MacKillop, Abraham A. Palmer
Journal: Nature Neuroscience (2017)
Caterpillar Sign in Infantile Hypertrophic Pyloric Stenosis
Authors: Bruno Martinez-Leo, Luis M Garcia-Cabello
Journal: New England Journal of Medicine (2017)

A 23-day-old male infant presented with nonbilious vomiting. Physical examination of the abdomen revealed a possible olive-sized mass, and imaging showed the “caterpillar” sign, which is suggestive of pyloric stenosis.
Make detaining patients who can’t pay their medical bills illegal
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Detaining patients who are unable to pay their healthcare bills should be made illegal with prosecutions for hospitals that break the law, global health specialists have said.

The phenomenon of imprisoning patients who have outstanding medical fees is common in several sub-Saharan African countries, including Cameroon, Democratic Republic of Congo, Ghana, Kenya, Nigeria, and Zimbabwe, as well as in India and Indonesia, according to a report from the Centre on Global Health Security at the think tank Chatham House in London.1

It’s difficult to say how many people are affected as there is very little research on this issue.

The report gives the …