tbuckley/cabot-search huggingface dataset:
Abstract 15237: Inhibition of the Kynurenine Pathway Improves Neurological Recovery in a Rat Model of Cardiac Arrest
Authors: Roberta Affatato, Jacopo Lucchetti, Sabina Ceriani, Francesca Fumagalli, Claudia Fracasso, Lidia Staszewsky, Teresa Letizia, Serge Masson, Marco Gobbi, Roberto Latini, Giuseppe Ristagno
Journal: Circulation (2015)

Introduction: Kynurenine pathway (KP), the major route of the tryptophan (TRP) catabolism, is involved in the pathogenesis of numerous cerebral disorders. We have previously demonstrated that KP is activated following cardiac arrest (CA) and correlates with neurological injury both in animals and humans. We thus hypothesized that inhibition of the enzyme initiating the TRP catabolism into kynurenine (KYN), i.e. indoleamine-2,3-dioxygenase (IDO), could prevent KP activation and improve neurological recovery. Methods: Twenty-two rats received oral administration of 1-Methyl-Tryptophan (1-MT, 800mg/Kg of racemate) (n=10) or corresponding vehicle (n=12), 24h and 2h before CA. Ventricular fibrillation was induced and untreated for 8 min. CPR was then performed for additional 8 min prior to defibrillation. Blood samples were obtained for assay of plasma levels of: 1-MT, TRP, KYN, high-sensitive cardiac troponin T (hs-cTnT), and neuron specific enolase (NSE). Rats were observed up to 96h for assessment of neurological recovery by the neurological deficit score (NDS). Results: High plasma levels of 1-MT were observed up to 96h after drug administration (Fig). CA induced a significant and long-lasting KP activation (reported as KYN/TRP) and this was significantly reduced in rats treated with 1-MT (Fig). 90% of animals treated with 1-MT were successfully resuscitated compared to 75% of those treated with vehicle. Lower levels of hs-cTnT (5186 vs. 9207 ng/L) and NSE (0.44 vs. 0.76 ng/mL) were observed in treated animals compared to vehicles. 1-MT also significantly reduced the KP activation in the hippocampus, restoring the KYN/TRP ratio to the values observed in naïve rats. The severity of CA-induced neurological deficit was significantly reduced by 1-MT (Fig), and correlated with level of KP activation, both in plasma (Fig) and in the hippocampus (r=0.73, p=0.019). Conclusions: In this model, inhibition of KP was feasible and improved neurological recovery after CA.
Stereotactic Body Radiotherapy (SBRT) or Surgery in Early Stage (I a II) Non Small Cell Lung Cancer (NSCLC)
Authors: Hirsh Koyi, Gunnar Hillerdal, Signe Friesland, Karl Gustav Kolbeck, Olov Andersson, Per Bergman, Lotta Orre, Per Liv, Eva Branden
Journal: Journal of Thoracic Oncology (2015)
Correction: Article on E2F7 in SCC: Figure 2.
Journal: Cancer Research (2009)

In the article on E2F7 in SCC in the March 1, 2009 issue of Cancer Research, data from murine keratinocytes was inadvertently shown instead of human epidermal keratinocytes. The corrected Fig. 2A appears below. The legend for Fig. 2A should read as follows: “A, the basal layer of the epidermis comprises TA keratinocytes and KSCs from which PMD keratinocytes of the suprabasal layers are derived. Cell fractions enriched for KSC, TA, and PMD cells were isolated from human epidermal tissue (Materials and Methods) based on their staining intensity for α6 (FITC-A) and CD71 (PE-A). Enriched fractions were reanalyzed and a representative merged image demonstrating the purity of the fractions is shown.” The conclusions and interpretation of the data in the article are unaltered by this correction.
<i>TLR7</i> escapes X chromosome inactivation in immune cells
Authors: Mélanie Souyris, Claire Cenac, Pascal Azar, Danièle Daviaud, Astrid Canivet, Solange Grunenwald, Catherine Pienkowski, Julie Chaumeil, José E. Mejía, Jean-Charles Guéry
Journal: Science Immunology (2018)

Biallelic TLR7 expression in immune cells may contribute to increased autoimmune disease risk in women.
Abstract 19784: Characterizing the Practice of Vascular Medicine at an Academic Medical Center
Authors: Maya Serhal, Nancy Nguyen, Ellen Brinza, Chris Bajzer, Philip Erwin, Natalie Evans, Natalia Fendrikova Mahlay, Marcelo Gomes, Deborah Hornacek, Douglas Joseph, Soo H Kim, Medhi Shishehbor, John R Bartholomew, Heather Gornik
Journal: Circulation (2016)

Introduction: There is increasing recognition of vascular medicine as a distinct subspecialty of internal medicine and cardiology. There are currently few vascular medicine training programs nation...
Efficacy and Safety of AR101 in Peanut Allergy: Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial (PALISADE)
Authors: Stacie M. Jones, Kirsten Beyer, A. Wesley Burks, Thomas B. Casale, Jonathan O'B. Hourihane, Annette Marcantonio, Andrea Vereda, Brian P. Vickery, Rezi Zawadzki, Daniel C. Adelman
Journal: Journal of Allergy and Clinical Immunology (2018)
IL-13 Mediates Skin Lipid Abnormalities in Atopic Dermatitis
Authors: Evgeny Berdyshev, Elena Goleva, Irina Bronova, Patricia A. Taylor, John Jung, Brittany Richers, Clifton F. Hall, Mingeum Jeong, Tao Zheng, Donald Y.M. Leung
Journal: Journal of Allergy and Clinical Immunology (2018)
Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in Non–Small Cell Lung Cancer
Authors: Harper G. Hubbeling, Emily F. Schapira, Nora K. Horick, Kelly E.H. Goodwin, Jessica J. Lin, Kevin S. Oh, Alice T. Shaw, William A. Mehan, Helen A. Shih, Justin F. Gainor
Journal: Journal of Thoracic Oncology (2018)
Keynote-200 phase 1b: A novel combination study of intravenously delivered coxsackievirus A21 and pembrolizumab in advanced cancer patients.
Authors: Hardev S. Pandha, Christy Ralph, Kevin Harrington, Brendan D. Curti, Rachel E. Sanborn, Wallace L. Akerley, Sumati Gupta, Charles M. Rudin, Jonathan E. Rosenberg, David Ross Kaufman, Emmett V. Schmidt, Mark Grose, Darren Shafren
Journal: Journal of Clinical Oncology (2017)

TPS3108 Background: Coxsackievirus A21 (CVA21, CAVATAK) is a naturally occurring ICAM-1 targeted oncolytic immunotherapeutic virus. Pembrolizumab is a human programmed death receptor-1 (PD-1) blocking antibody that has yielded significant solid tumor responses via reversal of tumor induced T-cell suppression. Intravenous (i.v.) CVA21 mono-therapy is generally well tolerated, with low toxicity and can successfully target tumors in patients with melanoma, NSCLC and bladder cancer as confirmed by detection of CVA21 viral RNA in post-treatment tumor biopsies (Pandha et al., 2016). Intratumoral CVA21 replication has the potential to up-regulate numerous key immune checkpoint molecules, including PD-L1 (Andtbacka et al., 2016).The combination of i.v. CVA21+pembrolizumab may translate to a potential enhanced benefit in the clinic. Methods: The Phase Ib KEYNOTE-200 (NCT02043665) Treatment: Primary objectives are to assess dose-limiting toxicities (DLT) of CVA21 in combination with pembrolizumab. Secondary objectives are to assess ORR by irRECIST 1.1 criteria, PFS, and OS. Patients (pts) are infused with CVA21 in 100 mL saline + pembrolizumab. In Cohort 1 (n = 3), CVA21 is administered at a dose of 1 x 10 8 TCID 50 , in Cohort 2 (n = 3) at a dose of 3 x 10 8 TCID 50 and in Cohort 3 (n = ~80) at a dose of 1 x 10 9 TCID 50 on study days 1,3,5,8,29,and Q3W for 6 additional infusions. Pembrolizumab is given in all cohorts at 200 mg IV Q3W from Day 8 for up to 2 years. Treatment (tx) with CVA21 + pembrolizumab will continue until confirmed CR or PD (whichever comes first) per irRECIST 1.1 or DLT.To date the combination of intravenous CVA21 and pembrolizumab has been generally well-tolerated. At present one gr 3 CVA21-related hyponatremia with no DLT for the combination of CVA21 and pembrolizumab being observed. Enrolment in Cohorts 1 and 2 is complete with tx of pts in Cohort 3 currently underway. Key eligibility: Pts with advanced disease considered appropriate tx with CVA21 + pembrolizumab, lesion(s) accessible for core biopsy, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression. Clinical trial information: NCT02043665.
Resolving Ethical Dilemmas in a Tertiary Care Veterinary Specialty Hospital: Adaptation of the Human Clinical Consultation Committee Model
Authors: Philip M. Rosoff, Jeannine Moga, Bruce Keene, Christopher Adin, Callie Fogle, Rachel Ruderman, Heather Hopkinso, Charity Weyhrauch
Journal: The American Journal of Bioethics (2018)

Technological advances in veterinary medicine have produced considerable progress in the diagnosis and treatment of numerous diseases in animals. At the same time, veterinarians, veterinary technicians, and owners of animals face increasingly complex situations that raise questions about goals of care and correct or reasonable courses of action. These dilemmas are frequently controversial and can generate conflicts between clients and health care providers. In many ways they resemble the ethical challenges confronted by human medicine and that spawned the creation of clinical ethics committees as a mechanism to analyze, discuss, and resolve disagreements. The staff of the North Carolina State University Veterinary Hospital, a specialty academic teaching institution, wanted to investigate whether similar success could be achieved in the tertiary care veterinary setting. We discuss the background and rationale for this method, as well as the approach that was taken to create a clinical ethics committee.
All plugged up — noninvasive mucus score to assess airway dysfunction in asthma
Authors: Steve N. Georas
Journal: Journal of Clinical Investigation (2018)

Asthma is remarkably heterogeneous, and there are multiple underlying inflammatory pathways and structural airway abnormalities that lead to symptomatic disease. Consequently, a current challenge in the field is to precisely characterize different types of asthma, with the goal of developing personalized approaches to therapy. In the current issue of the JCI, Dunican et al. developed a noninvasive way to assess airway dysfunction in asthma by measuring mucus accumulation using multidetector computed tomography (MDCT) and found that mucus plugging of small airways was remarkably common in subjects with severe asthma. This work highlights the importance of noninvasive imaging approaches in defining specific asthma subsets and guiding targeted therapies.
NCCN Guidelines Insights: T-Cell Lymphomas, Version 2.2018
Authors: Steven M. Horwitz, Stephen M. Ansell, Weiyun Z. Ai, Jeffrey Barnes, Stefan K. Barta, Michael Choi, Mark W. Clemens, Ahmet Dogan, John P. Greer, Ahmad Halwani, Bradley M. Haverkos, Richard T. Hoppe, Eric Jacobsen, Deepa Jagadeesh, Youn H. Kim, Matthew A. Lunning, Amitkumar Mehta, Neha Mehta-Shah, Yahurio Oki, Elise A. Olsen, Barbara Pro, Saurabh A. Rajguru, Satish Shanbhag, Andrei Shustov, Lubomir Sokol, Pallawi Torka, Ryan Wilcox, Basem William, Jasmine Zain, Mary A. Dwyer, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2018)

Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas.
Swiping Left on the Quantified Relationship: Exploring the Potential Soft Impacts
Authors: Lily Frank, Michał Klincewicz
Journal: The American Journal of Bioethics (2018)

John Danaher, Sven Nyholm, and Brian D. Earp's (2018) fascinating articleon potential ethical objections to the use of quantified relationship technologies contends that “there is no blanket objection to or knockdown argument against” their use (17). Although we agree with this conclusion and with their plea for further empirical study of these technologies, we argue that their discussion of the quantified relationship does not adequately consider potential soft impacts of quantified relationship technologies (QRT).
Abstract P194: Association of First Birth with Long-term Trajectories of Cardiovascular Health: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Sarah Uttal, Donald Lloyd-Jones, Hongyan Ning, Norrina Allen, Cora Lewis, Erica Gunderson, Lisa VanWagner
Journal: Circulation (2016)

Background: Pregnancy is the first major physiologic stress women will experience that may exacerbate cardiovascular risk factors. Little is known about how pregnancy impacts cardiovascular health (CVH), as defined by the AHA. We examined the effects of a first birth on trajectories of CVH in a community-based sample of biracial women. Methods: CARDIA is a longitudinal study of 5,115 black and white adults aged 18-30 years at enrollment (1985-86). CVH was defined as poor, intermediate and ideal levels of 6 of 7 available AHA factors (BMI, physical activity, smoking, blood pressure, glucose, and cholesterol) assigned scores of 0, 1, and 2, respectively. A modified CVH score (CVHS) was calculated as the sum of scores from individual health factors (range 0-14; higher score=greater CVH). We employed latent-class modeling to identify distinct trajectories in CVHS over 25 years of follow up after first birth. Results: Among 1,775 baseline nulliparas (59.1% white), 888 first live births occurred. In women with ≥1 birth (Figure 1a) and with no births (Figure 1b) there were 6 distinct CVHS trajectories and most tracked over time. Trajectory patterns were similar between women with and without a birth, and select groups experienced a rapid decline in CVHS (Figure 1a: groups 1,2,5; 1b: groups 1,2,3). There is no statistically significant difference in likelihood of group membership based on number of births or exam year of first birth (1a). Conclusion: Contrary to expectation, CVHS trajectories through adulthood do not differ markedly between women with and without live births. Future analyses among subgroups at risk for longer adverse effects are being evaluated.
α1-Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease
Authors: John M. Magenau, Steven C. Goldstein, Dan Peltier, Robert J. Soiffer, Thomas Braun, Attaphol Pawarode, Mary M. Riwes, Maggi Kennel, Joseph H. Antin, Corey S. Cutler, Vincent T. Ho, Edwin P. Alyea, Brian L. Parkin, Gregory A. Yanik, Sung Won Choi, Eli C. Lewis, Charles A. Dinarello, John Koreth, Pavan Reddy
Journal: Blood (2018)
Countdown to 2030: tracking progress towards universal coverage for reproductive, maternal, newborn, and child health
Authors: Ties Boerma, Jennifer Requejo, Cesar G Victora, Agbessi Amouzou, Asha George, Irene Agyepong, Carmen Barroso, Aluisio J D Barros, Zulfiqar A Bhutta, Robert E Black, Josephine Borghi, Kent Buse, Liliana Carvajal Aguirre, Mickey Chopra, Doris Chou, Yue Chu, Mariam Claeson, Bernadette Daelmans, Austen Davis, Jocelyn DeJong, Theresa Diaz, Shams El Arifeen, Fernanda Ewerling, Monica Fox, Stuart Gillespie, John Grove, Tanya Guenther, Annie Haakenstad, Ahmad Reza Hosseinpoor, Sennen Hounton, Luis Huicho, Troy Jacobs, Safia Jiwani, Youssouf Keita, Rajat Khosla, Margaret E Kruk, Taona Kuo, Catherine Kyobutungi, Ana Langer, Joy E Lawn, Hannah Leslie, Mengjia Liang, Blerta Maliqi, Alexander Manu, Honorati Masanja, Tanya Marchant, Purnima Menon, Allisyn C Moran, Oscar J Mujica, Devaki Nambiar, Kelechi Ohiri, Lois A Park, George C Patton, Stefan Peterson, Ellen Piwoz, Kumanan Rasanathan, Anita Raj, Carine Ronsmans, Ghada Saad-Haddad, Mariam L Sabin, David Sanders, Susan M Sawyer, Inacio Crochemore M da Silva, Neha S Singh, Kate Somers, Paul Spiegel, Hannah Tappis, Marleen Temmerman, Lara M E Vaz, Rajani R Ved, Luis Paulo Vidaletti, Peter Waiswa, Fernando C Wehrmeister, William Weiss, Danzhen You, Shehla Zaidi
Journal: The Lancet (2018)
Abstract 14536: Non-Invasive Evaluation of the Severity of Chronic Thromboembolic Pulmonary Hypertension With Ventilatory Gas Analysis
Authors: Mina Akizuki, Koichiro Sugimura, Tatsuo Aoki, Takaaki Kakihana, Osamu Ito, Hiroaki Shimokawa, Masahiro Kohzuki
Journal: Circulation (2016)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by organic thrombotic obstructions of pulmonary arteries, leading to reduced pulmonary vascular reserve and right ...
Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy
Authors: William C. Stafford, Xiaoxiao Peng, Maria Hägg Olofsson, Xiaonan Zhang, Diane K. Luci, Li Lu, Qing Cheng, Lionel Trésaugues, Thomas S. Dexheimer, Nathan P. Coussens, Martin Augsten, Hanna-Stina Martinsson Ahlzén, Owe Orwar, Arne Östman, Sharon Stone-Elander, David J. Maloney, Ajit Jadhav, Anton Simeonov, Stig Linder, Elias S. J. Arnér
Journal: Science Translational Medicine (2018)

Selective irreversible inhibitors of selenoprotein TXNRD1 yield anticancer efficacy without overt systemic toxicity in mouse models.
Abstract 90: Serum Kawasaki Disease-specific Microbe-associated Molecular Patterns are Derived from in Vitro and in Vivo Biofilms
Authors: Takeshi Kusuda, Yasutaka Nakashima, Murata Kenji, Shunsuke Kanno, Mitsumasa Saito, Tamami Tanaka, Yumi Mizuno, Kazunobu Ouchi, Kenji Waki, Toshiro Hara
Journal: Circulation (2015)

Background: We have found that serum KD-specific molecules possess molecular structures common to microbe-associated molecular patterns (MAMPs) from several bacteria by liquid chromatography-mass spectrometry (LC-MS) analysis. In the present study, we have extensively searched for the culture conditions that reproducibly produce MAMPs common to serum KD specific molecules. Methods: Yersinia pseudotuberculosis, spore-forming bacteria and pathogenic bacteria were obtained from KD patients. Others were purchased from American Type Culture Collection. Microbes were cultured in a variety of conditions (medium, temperature, duration, shaking and biofilm formation). For biofilm formation, a various kind of oil/butter was added to the culture medium. Extraction from in vitro samples (culture supernatants, bacteria cells, and biofilms) as well as in vivo biofilm samples (teeth, tongue, nasal cavity, or rectum) was performed with ethyl acetate. Samples were analyzed by HPLC and MS (Esquire 6000 electrospray ionization). Human coronary artery endothelial cells (HCAECs) were employed for cytokine assay. The concentrations of cytokines were measured by EC800 cell analyzer with a BD™ Cytometric Bead Array. Results: Serum KD-specific molecules showed m/z and MS/MS fragmentation patterns almost identical to those of MAMPs obtained from the biofilms formed in vitro (Bacillus cereus, Bacillus subtilis, Yersinia pseudotuberculosis, Staphylococcus aureus) or in vivo. Not culture supernatants but biofilm extracts from these bacteria, especially cultured in the presence of butter, induced proinflammatory cytokines by HCAECs. Conclusions: Extensive analysis by LC-MS/MS revealed that serum KD-specific molecules common to MAMPs were mostly derived from biofilms in vitro and in vivo. This report offers novel insight into the pathogenesis of KD.
Abstract 10961: QRS Duration and Left Bundle Branch Block Do Not Deter Assessment of Low Voltage in Cardiac Amyloidosis
Authors: Brett W Sperry, Michael N Vranian, Hariom Joshi, Rory Hachamovitch, Mazen Hanna
Journal: Circulation (2015)

Introduction: Left bundle branch block (LBBB) with QRS duration &gt; 120 msec is typically associated with increased ECG voltage without a necessary increase in left ventricular wall thickness. Studies assessing voltage criteria in amyloidosis and other cardiomyopathies have excluded patients with LBBB. We sought to assess the effects of QRS duration and LBBB on voltage criteria in cardiac amyloidosis. Methods: We performed a retrospective analysis of patients with newly diagnosed cardiac amyloidosis at our institution from 2001-2014. Low voltage in the precordial leads was defined by the Sokolow criteria (S wave in V1 plus R wave in V5 or V6 ≤ 15mm). Limb lead voltage was calculated by the sum of the entire QRS complex voltage of leads I, II and III with low voltage being defined as each lead ≤ 5 mm. Patients with left bundle branch block were propensity matched to assess voltage criteria based upon age, sex, history of HTN, amyloid type (AL vs TTR), anteroseptal thickness and BSA to those with QRS &lt; 120msec. Results: In 299 subjects (age 69.6 +/- 11.7 years, male 69%, HTN 53%, AL 53%, IVS 18.1 +/- 4.1 mm, BSA 1.95 +/- 0.26, EF 48 +/- 14%), mean QRS duration was 107 +/- 25 msec with 71 patients (24%) having a QRS duration greater than 120 msec (17 LBBB). The average limb voltage was 15.1 +/- 7.3 mm with low limb lead voltage seen in 62% of patients. Low precordial lead voltage was found in 73% of patients with a mean Sokolow voltage of 12.9 +/- 7.5 mm. After propensity matching the 17 patients with LBBB on a 1:3 basis with patients with a narrow complex QRS, there was no difference in any measure of voltage criteria. Conclusion: LBBB is not associated with higher voltage and does not hinder the ability to detect low voltage in patients with cardiac amyloidosis.
Abstract 21041: Cardiac Resynchronization Therapy for Pacemaker Induced Cardiomyopathy Results in Super Response
Authors: Ridhima Kapoor, Sudhi Tyagi, Judy Fox, Michael Widlansky, James Roth, James Oujiri, Jason Rubenstein, Marcie Berger
Journal: Circulation (2017)

Background: Sustained right ventricular (RV) pacing can cause cardiomyopathy due to electrical dyssynchrony. Cardiac resynchronization therapy (CRT) can lead to reverse left ventricular (LV) remodeling by minimizing conduction delay. We hypothesized that CRT in pacemaker induced cardiomyopathy (PICM) would result in a greater improvement in EF compared to other causes of cardiomyopathy. Objective: To determine the change in ejection fraction after CRT upgrade in patients with PICM. Methods: A retrospective EMR review was conducted for individuals who underwent CRT upgrade between January 1, 2010 and January 31, 2016. Inclusion criteria were normal EF prior to pacemaker placement, RV pacing ≥ 80% and EF ≤ 45% prior to CRT upgrade. Frequency of improvement in EF of greater than or equal to 5% and 10% were calculated. Results: The study population included 22 patients with average age 69.7 ± 13.1 and average EF of 36.8 ± 6.9% at the time of CRT upgrade. Eight patients had aortic stenosis prior to CRT upgrade. Sixteen patients (73%) experienced at least 5% improvement in EF one year after upgrade to CRT and 12 patients (55%) improved by at least 10%. Average change in EF was 9.2 ± 12.3% compared to 4.6% improvement in all-comers with heart failure in the MIRACLE study. Ninety-two percent of participants without aortic stenosis had improvement in EF of at least 10% or to greater than 50% compared to only 8.3% of participants with aortic stenosis experiencing this degree of improvement (p=0.002). Conclusion: In patients with PICM, EF improvement after CRT upgrade is higher than in all-comers. Furthermore, the presence of concomitant aortic stenosis was associated with an attenuated improvement in EF.
Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium
Authors: Sicai Zhang, Francois Lebreton, Michael J. Mansfield, Shin-Ichiro Miyashita, Jie Zhang, Julia A. Schwartzman, Liang Tao, Geoffrey Masuyer, Markel Martínez-Carranza, Pål Stenmark, Michael S. Gilmore, Andrew C. Doxey, Min Dong
Journal: Cell Host & Microbe (2018)