tbuckley/cabot-search huggingface dataset:
Abstract 13056: Endoplasmic Reticulum-Resident Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding in Cardiac Fibroblasts
Authors: Chao-Ling Chen, Yin-Chun Shi, Yan Zhang, Rebecca L Mellor, Evelyn M Kanter, Yun Fang, Chen-Ting Hung, Jing-Yi Nong, Kathryn A Yamada, Jeanne M Nerbonne, Kai-Chien Yang
Journal: Circulation (2016)

Introduction: Cardiac fibrosis plays a critical role in fostering heart failure (HF). Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited. Exploiting RNA sequencing data from human failing heart and co-expression gene network analysis, we identified thioredoxin domain containing 5 (TXNDC5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum (ER) protein, as a potential novel mediator of cardiac fibrosis. The goal of this study was to test this hypothesis directly. Results: TXNDC5 mRNA and protein were highly upregulated in human failing heart and in the left ventricle (LV) from a mouse model of isoproterenol (ISO)-induced HF. Cardiac TXNDC5 expression showed strong positive correlation with that of ECM protein genes. TXNDC5 increased in CF upon transforming growth factor β (TGFβ) stimulation. Knocking down TXNDC5 in CF abrogated TGFβ-induced ECM protein upregulation and myofibroblast transformation independent of SMAD3 activity. Forced expression of TXNDC5 triggered activation of CF and increased ECM protein production. Further experiments revealed that TXNDC5, a protein disulfide isomerase, facilitated proper ECM protein folding; depletion of TXNDC5 led to ECM protein misfolding and degradation through ER-associated degradation (ERAD) pathway. In addition, TGFβ-induced TXNDC5 upregulation in CF was dependent on increased ER stress and activating transcription factor 6 (ATF6)-mediated regulation. Knocking out TXNDC5 by CRISPR/Cas9 genome editing showed cardioprotective effects including reduced cardiac fibrosis (by 36%), preserved LV contractility (post-ISO LV ejection fraction in WT 40.1±2.6 vs KO 57.5±5.1, P &lt;0.001) and improved survival in mice with ISO-induced HF. Conclusion: ER resident protein TXNDC5 promotes cardiac fibrosis by increasing CF activity and ECM production through facilitating ECM protein folding. Genetic deletion of TXNDC5 protects against β agonist-induced cardiac fibrosis and LV dysfunction. Targeting TXNDC5, therefore, could be a novel approach to mitigate excessive ECM accumulation and fibrosis formation during HF.
Delivery outcomes in term births after bariatric surgery: Population-based matched cohort study
Authors: Olof Stephansson, Kari Johansson, Jonas Söderling, Ingmar Näslund, Martin Neovius
Journal: PLoS Medicine (2018)

Background Obesity increases the risk of adverse delivery outcomes. Whether weight loss induced by bariatric surgery influences these risks remains to be determined. The objective was to investigate the risk of adverse delivery outcomes among post-surgery women compared with women without bariatric surgery history but with similar characteristics. Methods and findings We identified 801,443 singleton live-born term births (≥37 gestational weeks) in the Swedish Medical Birth Register between 1 January 2006 and 31 December 2013, of which 1,929 were in women with a history of bariatric surgery and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. For each post-surgery delivery, up to 5 control deliveries were matched by maternal pre-surgery BMI (early-pregnancy BMI used for controls), age, parity, smoking, education, height, country of birth, and delivery year (N post-surgery deliveries:matched controls = 1,431:4,476). The main outcome measures were mode of delivery, induction of labor, post-term pregnancy (≥42 + 0 gestational weeks), epidural analgesia, fetal distress, labor dystocia, peripartum infection, obstetric anal sphincter injury (perineal tear grade III–IV), and postpartum hemorrhage. Among the women with a history of bariatric surgery, the mean pre-surgery BMI was 42.6 kg/m2, the median surgery-to-conception interval was 1.4 years, and the mean BMI loss between surgery and early pregnancy was 13.5 kg/m2 (38 kg). Compared to matched control women, post-surgery women were less likely to have cesarean delivery (18.2% versus 25.0%, risk ratio [RR] 0.70, 95% CI 0.60–0.80), especially emergency cesarean (6.8% versus 15.1%, RR 0.40, 95% CI 0.31–0.51). Post-surgery women also had lower risks of instrumental delivery (5.0% versus 6.5%, RR 0.73, 95% CI 0.53–0.98), induction of labor (23.4% versus 34.0%, RR 0.68, 95% CI 0.59–0.78), post-term pregnancy (4.2% versus 10.3%, RR 0.40, 95% CI 0.30–0.53), obstetric anal sphincter injury (1.5% versus 2.9%, RR 0.46, 95% CI 0.25–0.81), and postpartum hemorrhage (4.6% versus 8.0%, RR 0.58, 95% CI 0.44–0.76). Since this study was not randomized, a limitation is the possibility of selection bias, despite our efforts using careful matching. Conclusions Bariatric-surgery-induced weight loss was associated with lower risks for adverse delivery outcomes in term births.
Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial
Authors: Gregg W Stone, Stephen G Ellis, Tommaso Gori, D Christopher Metzger, Bernardo Stein, Matthew Erickson, Jan Torzewski, Jerome Williams, William Lawson, Thomas M Broderick, Ameer Kabour, Guy Piegari, Jeffrey Cavendish, Barry Bertolet, James W Choi, Steven O Marx, Philippe Généreux, Dean J Kereiakes
Journal: The Lancet (2018)
Abstract 15068: Impact of Out-stent Plaque Vulnerability on Neointimal Stent Coverage in Patients with Acute Coronary Syndrome: Intracoronary Angioscopic and Ultrasonic Quantification
Authors: Kenji Kawai, Minoru Ichikawa, Takashi Takagi, Mitsutoshi Asai, Yoshizumi Takei, Kenji Fukuda, Shohei Yoshima, Takeshi Oshita, Yoshiyuki Kijima
Journal: Circulation (2014)

Background: Intracoronary angioscopy is a unique imaging device to visualize in-stent neointimal coverage (ISNC). iMAP intravascular ultrasound (IVUS) quantitates not only plaque burden but also it...
An Automated Grading System for Detection of Vision-Threatening Referable Diabetic Retinopathy on the Basis of Color Fundus Photographs
Authors: Zhixi Li, Stuart Keel, Chi Liu, Yifan He, Wei Meng, Jane Scheetz, Pei Ying Lee, Jonathan Shaw, Daniel Ting, Tien Yin Wong, Hugh Taylor, Robert Chang, Mingguang He
Journal: Diabetes Care (2018)

The goal of this study was to describe the development and validation of an artificial intelligence-based, deep learning algorithm (DLA) for the detection of referable diabetic retinopathy (DR).A DLA using a convolutional neural network was developed for automated detection of vision-threatening referable DR (preproliferative DR or worse, diabetic macular edema, or both). The DLA was tested by using a set of 106,244 nonstereoscopic retinal images. A panel of ophthalmologists graded DR severity in retinal photographs included in the development and internal validation data sets (n = 71,043); a reference standard grading was assigned once three graders achieved consistent grading outcomes. For external validation, we tested our DLA using 35,201 images of 14,520 eyes (904 eyes with any DR; 401 eyes with vision-threatening referable DR) from population-based cohorts of Malays, Caucasian Australians, and Indigenous Australians.Among the 71,043 retinal images in the training and validation data sets, 12,329 showed vision-threatening referable DR. In the internal validation data set, the area under the curve (AUC), sensitivity, and specificity of the DLA for vision-threatening referable DR were 0.989, 97.0%, and 91.4%, respectively. Testing against the independent, multiethnic data set achieved an AUC, sensitivity, and specificity of 0.955, 92.5%, and 98.5%, respectively. Among false-positive cases, 85.6% were due to a misclassification of mild or moderate DR. Undetected intraretinal microvascular abnormalities accounted for 77.3% of all false-negative cases.This artificial intelligence-based DLA can be used with high accuracy in the detection of vision-threatening referable DR in retinal images. This technology offers potential to increase the efficiency and accessibility of DR screening programs.
UCH-L1 bypasses mTOR to promote protein biosynthesis and is required for MYC-driven lymphomagenesis in mice
Authors: Sajjad Hussain, Tibor Bedekovics, Qiuying Liu, Wenqian Hu, Haeseung Jeon, Sarah H. Johnson, George Vasmatzis, Danielle G. May, Kyle J. Roux, Paul J. Galardy
Journal: Blood (2018)
Evaluating Artificial Intelligence Applications in Clinical Settings
Authors: Elaine O. Nsoesie
Journal: JAMA Network Open (2018)

Yogesan Kanagasingam, PhD; Di Xiao, PhD; Janardhan Vignarajan, BSc (Hons); Amita Preetham, MD; Mei-Ling Tay-Kearney, MD; Ateev Mehrotra, MD
Abstract 20554: Human iPS Derived Proepicardial Cells Enhance Cardiomyocyte Function and Organoid Structure
Authors: Jun Jie Tan, Jacques P Guyette, Ling Xiao, David J Milan, Harald C Ott
Journal: Circulation (2017)

Introduction: Proepicardial cells (PECs) originate from the proepicardial organ, which envelopes the heart during development to become the epicardium. PECs integrate with the adjacent myocardium t...
HOXA9 Reprograms the Enhancer Landscape to Promote Leukemogenesis
Authors: Yuqing Sun, Bo Zhou, Fengbiao Mao, Jing Xu, Hongzhi Miao, Zhenhua Zou, Le Tran Phuc Khoa, Younghoon Jang, Sheng Cai, Matthew Witkin, Richard Koche, Kai Ge, Gregory R. Dressler, Ross L. Levine, Scott A. Armstrong, Yali Dou, Jay L. Hess
Journal: Cancer Cell (2018)
Fyn kinase is a novel modulator of erythropoietin signaling and stress erythropoiesis
Authors: Elisabetta Beneduce, Alessandro Matte, Luigia De Falco, Serge Mbiandjeu, Deborah Chiabrando, Emanuela Tolosano, Enrica Federti, Sara Petrillo, Narla Mohandas, Angela Siciliano, Wilson Babu, Vijay Menon, Saghi Ghaffari, Achille Iolascon, Lucia De Franceschi
Journal: American Journal of Hematology (2018)

Abstract The signaling cascade induced by the interaction of erythropoietin (EPO) with its receptor (EPO‐R) is a key event of erythropoiesis. We present here data indicating that Fyn, a Src‐family‐kinase, participates in the EPO signaling‐pathway, since Fyn −/− mice exhibit reduced Tyr‐phosphorylation of EPO‐R and decreased STAT5‐activity. The importance of Fyn in erythropoiesis is also supported by the blunted responsiveness of Fyn −/− mice to stress erythropoiesis. Fyn −/− mouse erythroblasts adapt to reactive oxygen species (ROS) by activating the redox‐related‐transcription‐factor Nrf2. However, since Fyn is a physiologic repressor of Nrf2, absence of Fyn resulted in persistent‐activation of Nrf2 and accumulation of nonfunctional proteins. ROS‐induced over‐activation of Jak2‐Akt‐mTOR‐pathway and repression of autophagy with perturbation of lysosomal‐clearance were also noted. Treatment with Rapamycin, a mTOR‐inhibitor and autophagy activator, ameliorates Fyn −/− mouse baseline erythropoiesis and erythropoietic response to oxidative‐stress. These findings identify a novel multimodal action of Fyn in the regulation of normal and stress erythropoiesis.
Using ASCO QOPI and the QTP as an improvement model in a small safety net cancer center.
Authors: Crystal Simmons, Steve Power
Journal: Journal of Clinical Oncology (2018)

78 Background: Organizational change is challenging in a well-resourced large academic cancer center. Such challenges are greater in a resource-constrained safety net cancer center. This project sought to learn how the combination of ASCO QOPI data submission and the Quality Training Program (QTP) could assist JPS with implementing a quality improvement project. Methods: The results from QOPI data submissions for Fall 2016 and Spring 2017 indicated opportunity in the area of oral chemotherapy education. This was prioritized due to increasing use of oral chemotherapy and relatively poor adherence data nationally 1,2 . The team recognized the relatively low sample size in the QOPI results and supplemented the data with additional abstraction to validate the original hypothesis. Following the structure provided by the QTP enabled JPS to focus its limited resources on understanding the existing process and formally interrogating it to determine the key causes of the problem. Additional information was obtained from the provider team via the use of an online survey. The team found that no single intervention would achieve the goals of improving the metric to above the QOPI mean they implemented small changes over time. These included reducing variation in ordering processes by defaulting to an electronic method; adding the Via oral chemotherapy protocols to the EMR; and developing and deploying a pre-chemotherapy checklist. The team learned that continual reinforcement and inquiry was necessary to ensure the effectiveness of some interventions. Results: Post-implementation results revealed improvements beyond the targeted measure. Approaching the problem systematically and methodically deploying solutions, the team observed improvements in multiple related oral chemotherapy QOPI measures. Conclusions: Meaningful change can result from the ASCO QOPI data and QTP combination in a safety net cancer center. Projects need to start small and remain focused. Challenges to implementing QI in a resource limited environment remain; however, these can be addressed with a methodical approach and strong support from leadership.
Huge Abdominal Photopenic Area Due to Kidney Cyst Imaged by Bone Scintigraphy in a Prostate Cancer Patient
Authors: Chrissa Sioka, Evangelia Gkika, Athanasios Paliouras, John Giannakis, Andreas Fotopoulos
Journal: Clinical Nuclear Medicine (2018)

Bone scintigraphy is a method of choice in evaluating metastatic disease in patients with prostatic cancer. We describe the case of a 77-year-old man who was subjected to bone scan for evaluation of secondary metastatic disease due to an elevated prostatic-specific antigen level (7.2). Bone scintigraphy demonstrated a huge photopenic area in the left upper abdominal area, as a result of a huge kidney cyst (15 × 13 cm).
Social workers first-time treatment assessment.
Authors: Christa Poole, Tori Nelson, Jacqueline Barnes, Angela Clay, Erica Coyle, Juliette Dimitrov, Emily Douglas, Brittany Golias, Rene Barrat-Gordon, IIana Spaulding, Rebecca Zeiter, Cheryl M Carrino, Andrew Rothacker, Rosemary Truchanowicz, Chad W. Cummings
Journal: Journal of Clinical Oncology (2018)

164 Background: Supporting emotional, psychological, financial and spiritual well-being of patients has been shown to have a positive impact on quality of life and patient experience. Social workers in our outpatient cancer center are responsible for completing new patient assessments at the start of chemotherapy treatment to provide early access to psychosocial support services. Assessments are to be completed within three weeks of the patient’s first chemotherapy treatment. Connecting with patients early in the care experience allows social workers to proactively assist with education, support and link patients to vital resources. Methods: Completed assessments were tracked and from October through December 2017. The social workers leveraged the use of data analytics and a team based approach to increase the number of new patient assessments completed within the first 3 weeks of chemotherapy. Weekly 30-minute huddles were held using problem solving methods, including brain storming, cause and effect diagrams, force ranking, and polling. Results: A team identified 39 potential causes to why 65.14% of patients were not receiving assessments within the first 3 weeks of chemotherapy treatment. Potential causes were grouped and themed. Work prioritization, inconsistent methods of identifying patients receiving chemotherapy for the first time, and lack of visual management to monitor progress of this metric were identified as key objectives for improvement. Countermeasures were developed and implemented; a dashboard was created to analyze the first time treatment assessment completion percentages by disease group and standardizing the process of notifying social workers of patients in need of an assessment. Social worker assessment completion rates improved from 34.78% (December 2017) to 75.35% (April 2018). Conclusions: This project demonstrates the value of utilizing problem solving, visual management, and data analytics for continuous quality improvement projects related to clinical care and processes. Cross-disciplinary collaboration should be explored with the use of visual tools and other resources to facilitate communication that is understood by all disciplines.
Characteristics of Spontaneous Spinal Cord Infarction and Proposed Diagnostic Criteria
Authors: Nicholas L. Zalewski, Alejandro A. Rabinstein, Karl N. Krecke, Robert D. Brown, Eelco F. M. Wijdicks, Brian G. Weinshenker, Timothy J. Kaufmann, Jonathan M. Morris, Allen J. Aksamit, J. D. Bartleson, Giuseppe Lanzino, Melissa M. Blessing, Eoin P. Flanagan
Journal: JAMA Neurology (2018)

Spinal cord infarction (SCI) is often disabling, and the diagnosis can be challenging without an inciting event (eg, aortic surgery). Patients with a spontaneous SCI are often misdiagnosed as having transverse myelitis. Diagnostic criteria for SCI are lacking, hindering clinical care and research.To describe the characteristics of spontaneous SCI and propose diagnostic criteria.An institution-based search tool was used to identify patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1997 to December 2017 with a spontaneous SCI. Patients provided written consent to use their records for research. Participants were 18 years and older with a diagnosis of spontaneous SCI (n = 133), and controls were selected from a database of alternative myelopathy etiologies for validation of the proposed diagnostic criteria (n = 280).A descriptive analysis of SCI was performed and used to propose diagnostic criteria, and the criteria were validated.Of 133 included patients with a spontaneous SCI, the median (interquartile range) age at presentation was 60 (52-69) years, and 101 (76%) had vascular risk factors. Rapid onset of severe deficits reaching nadir within 12 hours was typical (102 [77%]); some had a stuttering decline (31 [23%]). Sensory loss occurred in 126 patients (95%), selectively affecting pain/temperature in 49 (39%). Initial magnetic resonance imaging (MRI) spine results were normal in 30 patients (24%). Characteristic MRI T2-hyperintense patterns included owl eyes (82 [65%]) and pencil-like hyperintensity (50 [40%]); gadolinium enhancement (37 of 96 [39%]) was often linear and located in the anterior gray matter. Confirmatory MRI findings included diffusion-weighted imaging/apparent diffusion coefficient restriction (19 of 29 [67%]), adjacent dissection/occlusion (16 of 82 [20%]), and vertebral body infarction (11 [9%]). Cerebrospinal fluid showed mild inflammation in 7 of 89 patients (8%). Diagnostic criteria was proposed for definite, probable, and possible SCI of periprocedural and spontaneous onset. In the validation cohort (n = 280), 9 patients (3%) met criteria for possible SCI, and none met criteria for probable SCI.This large series of spontaneous SCIs provides clinical, laboratory, and MRI clues to SCI diagnosis. The diagnostic criteria proposed here will aid clinicians in making the correct diagnosis and ideally improve future care for patients with SCI. The validation of these criteria supports their utility in the evaluation of acute myelopathy.
Abstract 17370: Precise Measures of Insulin Sensitivity, Adiposity, and Cardiorespiratory Fitness Explain Differences in Insulin Resistance Between South Asians and Europeans
Authors: Shirin Zarafshar, Meera Srinivasan, Khin N Chan, John Giacomini, Monica Divakaruni, Jonathan N Myers, Latha Palaniappan, Fahim Abbasi, Themistocles L Assimes
Journal: Circulation (2016)

Introduction: South Asians (SAs) are more insulin resistant (IR) and at substantially higher risk of Type 2 diabetes and coronary artery disease compared to Europeans (EURs). Whether SAs possess a ...
CBP Modulates Sensitivity to Dasatinib in Pre-BCR+ Acute Lymphoblastic Leukemia
Authors: Jesús Duque-Afonso, Chiou-Hong Lin, Kyuho Han, David W. Morgens, Edwin E. Jeng, Ziming Weng, Johan Jeong, Stephen Hon Kit Wong, Li Zhu, Michael C. Wei, Hee-Don Chae, Martin Schrappe, Gunnar Cario, Justus Duyster, Xiangshu Xiao, Kathleen M. Sakamoto, Michael C. Bassik, Michael L. Cleary
Journal: Cancer Research (2018)

Dasatinib is a multi-tyrosine kinase inhibitor approved for treatment of Ph
Improved acute pain management in oncology patients using early scheduled contact with a pain coach.
Authors: Johanna M. LaSala, Anne C. Chiang, Kimberly M Severino
Journal: Journal of Clinical Oncology (2018)

293 Background: Pain control is a challenging balance in the ambulatory oncology practice. Standard methods of pain reassessment resulted in poor pain control in the majority of patients given prescriptions for narcotics. We developed a proactive reassessment of pain using patient reported outcomes and a coach to assist in medication usage. The aim was to decrease the time to reassessment of pain to fewer than 5 days and achieve acceptable pain control in greater than 50% of patients receiving new narcotic prescriptions in an ambulatory oncology setting. Methods: Patients receiving a new narcotic prescription or a new dose were provided with a pain diary and an appointment with their pain coach at 48 hours. Using a standard pain scale 1-10, patients’ pain scores were recorded by the patient in their pain diary and communicated via nurse/patient phone contact at 48 hour intervals. Dosing intervention by the patient’s oncologist was made for unacceptable pain and reassessed at 48 hours. Uncontrolled pain at 96 hours was followed by in person appointment with the oncologist. Pain scores and days to reassessment were recorded using an Excel data collection tool for patients receiving new or dose adjusted narcotic prescriptions between August and December31, 2017. Results: There were 17 patients encounters where the patient received a new prescription or a dose change from August 1- Dec 31, 2017. Reassessment of pain was achieved in 100% of patients in fewer than 5 days. The average time was 2.6 days (range 2-4). Acceptable pain control (pain scores 0-3) at the time of reassessment was achieved in 53% of patients. Conclusions: Cancer related pain is an ongoing challenge in oncology practices. Barriers include lack of planned follow-up and patient education. The institution of a pain coach, pain diary and scheduled contact decreased the time to reassessment of pain and decreased pain scores during short interval reassessment periods achieving better pain control in 50% of patients during the evaluated period. Quality interventions in ambulatory settings are achievable though multiple patient interactions and record keeping require additional staffing resources to sustain this change.