tbuckley/cabot-search huggingface dataset:
Transforming a cancer center into a high reliability organization.
Authors: Anna C. Pavlick, Kathleen C. Duffy Fray, Annette C. Rabinovich, Benjamin C. Wertheimer
Journal: Journal of Clinical Oncology (2019)

234 Background: The goals of a high reliability organization (HRO) are to eliminate preventable harm and streamline processes to maximize efficiency. The NYU Langone Medical Center embarked upon transforming the entire organization into an HRO. Educating the staff of the NYU Perlmutter Clinical Cancer Center (NYUPCCC) about the principles of HRO and a stepwise rollout began in March 2018. Methods: All cancer center employees were provided with an anonymous survey designed to assess culture, teamwork and burnout. Response rate to the survey was 83%. The survey evaluated 8 areas: improvement readiness, local leadership, teamwork climate, safety climate, decision making, burnout climate, personal burnout and emotional recovery. Three areas of opportunity were identified: teamwork and communication, discussing and correcting errors and participation in decision-making. Implementation and onboarding of the NYUPCCC occurred in 3 phases due to the physical layout of the center. Infusion floors were paired with physician floors that utilized them. Three “aims” for each floor were proposed with one aim being an overlapping aim that would require collaboration between the treatment and physician floors. Weekly “huddles” at a white board occur at a defined time and is led by a different staff member each week. This 15-minute gathering of all floor staff allows for an open exchange of ideas, verbalization of new areas of improvement and staff acknowledgement who provided a service above and beyond expectations. Initiatives and results will be presented. Results: This initiative had a positive impact on culture, improved staff-wide communication, improved physician efficacy and decreased patient wait times through the utilization of staff generated ideas and processes. It identified the need for better physician engagement. It also identified a data collection challenge so that information could be gathered in real time and metrics analyzed promptly. Conclusions: Transforming the NYUPCCC into an HRO identified opportunities for staff to encourage a culture of acceptance, foster teamwork, enhance overall cancer center communication and streamline processes to maximize patient safety and overall system efficiency.
A universal artificial intelligence platform for collaborative management of cataracts
Authors: Xiaohang Wu, Yelin Huang, Zhenzhen Liu, Weiyi Lai, Erping Long, Kai Zhang, Jiewei Jiang, Duoru Lin, Kexin Chen, Tongyong Yu, Dongxuan Wu, Cong Li, Yanyi Chen, Minjie Zou, Chuan Chen, Yi Zhu, Chong Guo, Xiayin Zhang, Ruixin Wang, Yahan Yang, Yifan Xiang, Lijian Chen, Congxin Liu, Jianhao Xiong, Zongyuan Ge, Dingding Wang, Guihua Xu, Shaolin Du, Chi Xiao, Jianghao Wu, Ke Zhu, Danyao Nie, Fan Xu, Jian Lv, Weirong Chen, Yizhi Liu, Haotian Lin
Journal: The Lancet (2019)
Medication reconciliation practices in ambulatory cancer care across Canada.
Authors: Ernie Mak, Melanie Lynn Powis, Celina Dara, Genevieve Bouchard-Fortier, Vishal Kukreti, Terri Stuart-McEwan, Hemangi Dave, Ryan Lawrence Kirkby, Jean-Pierre Bissonnette, Victoria Glinsky, Doris Howell, Anet Julius, Alyssa Macedo, Lyndon Morley, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2019)

248 Background: Substantial work has been done to implement medication reconciliation (MedRec) in the inpatient setting to reduce medical errors and drug discrepancies. However, this work has not extended to the ambulatory cancer setting, where care spans multiple providers and responsibility remains unclear. We undertook an environmental scan to understand current MedRec practices in ambulatory cancer care across Canada. Methods: Semi-structured telephone interviews were conducted with stakeholders from institutions across Canada during a 2-month period in 2019. Questionnaires were pre-circulated to participants to guide discussions. Questions probed participants on processes, policies, roles and responsibilities, definitions of target populations, information sources, and barriers and facilitators. Results: 21 of the 23 stakeholders contacted were interviewed, representing 9 of 10 Provinces. Most institutions had a process in place for collecting best possible medication history (BPMH; 81%); however, considerable variation in practice was noted and full MedRec was uncommon. Of those institutions with a process, BPMH was most often undertaken by a pharmacist or pharmacy tech (53%) using a comprehensive Provincial drug information system (65%) as a starting point, and targeted patients initiating systemic therapy (59%). Few institutions (22%) routinely collected performance measures evaluating the process or outcomes. Lack of resources (physical, human and financial), high patient volumes, and access to medication records from external institutions and community pharmacies were identified as significant barriers to routinely collecting BPMH. Understanding the value added, clinician buy-in, and patient education regarding the importance of bringing medication to the clinic were identified as facilitators. Leveraging patients to more actively participate in collection and maintenance of their own medication records was identified as an area for future work. Conclusions: While most centres were doing BPMH in some patients, MedRec was uncommon in the ambulatory cancer setting. Results indicate a lack of consensus regarding best practices for medication management in ambulatory cancer care.
circRNA circAF4 functions as an oncogene to regulate MLL-AF4 fusion protein expression and inhibit MLL leukemia progression
Authors: Wei Huang, Ke Fang, Tian-Qi Chen, Zhan-Cheng Zeng, Yu-Meng Sun, Cai Han, Lin-Yu Sun, Zhen-Hua Chen, Qian-Qian Yang, Qi Pan, Xue-Qun Luo, Wen-Tao Wang, Yue-Qin Chen
Journal: Journal of Hematology & Oncology (2019)

Abstract Background Circular RNAs (circRNAs) represent a type of endogenous noncoding RNAs that are generated by back-splicing events and favor repetitive sequences. Recent studies have reported that cancer-associated chromosomal translocations could juxtapose distant complementary repetitive intronic sequences, resulting in the aberrant formation of circRNAs. However, among the reported fusion genes, only a small number of circRNAs were found to originate from fusion regions during gene translocation. We question if circRNAs could also originate from fusion partners during gene translocation. Methods Firstly, we designed divergent primers for qRT-PCR to identify a circRNA circAF4 in AF4 gene and investigated the expression pattern in different types of leukemia samples. Secondly, we designed two small interfering RNAs specially targeting the back-spliced junction point of circAF4 for functional studies. CCK8 cell proliferation and cell cycle assay were performed, and a NOD-SCID mouse model was used to investigate the contribution of circAF4 in leukemogenesis. Finally, luciferase reporter assay, AGO2 RNA immunoprecipitation (RIP), and RNA Fluorescent in Situ Hybridization (FISH) were performed to confirm the relationship of miR-128-3p, circAF4, and MLL - AF4 expression. Results We discovered a circRNA, named circAF4, originating from the AF4 gene, a partner of the MLL fusion gene in MLL - AF4 leukemia. We showed that circAF4 plays an oncogenic role in MLL - AF4 leukemia and promotes leukemogenesis in vitro and in vivo. More importantly, knockdown of circAF4 increases the leukemic cell apoptosis rate in MLL - AF4 leukemia cells, while no effect was observed in leukemia cells that do not carry the MLL - AF4 translocation. Mechanically, circAF4 can act as a miR-128-3p sponge, thereby releasing its inhibition on MLL - AF4 expression. We finally analyzed most of the MLL fusion genes loci and found that a number of circRNAs could originate from these partners, suggesting the potential roles of fusion gene partner-originating circRNAs (named as FP-circRNAs) in leukemia with chromosomal translocations. Conclusion Our findings demonstrate that the abnormal elevated expression of circAF4 regulates the cell growth via the circAF4/miR-128-3p/MLL-AF4 axis, which could contribute to leukemogenesis, suggesting that circAF4 may be a novel therapeutic target of MLL - AF4 leukemia.
Clinical and epidemiological characteristics of Coxsackievirus A6- and Enterovirus 71-associated clinical stage 2 and 3 severe hand, foot, and mouth disease in Guangxi, Southern China, 2017
Authors: Yu Ju, Zhenlian Tan, Hao Huang, Minmei Chen, Yi Tan, Chao Zhang, Jin Wang, Hong Wang, Min Chen
Journal: Journal of Infection (2019)
Characteristics associated with hospitalization for patients with cancer receiving chemotherapy who present to the emergency department (ED).
Authors: Ryan David Nipp, Chinenye Azoba, Austin Vyas, Paul Kay, Charn-Xin Fuh, Irene Wang, Minh Mai, Margaret Soriano, Therese Marie Mulvey
Journal: Journal of Clinical Oncology (2019)

23 Background: Patients with cancer receiving chemotherapy often present to the ED and require hospitalization to manage acute issues. However, little work has sought to understand characteristics associated with hospitalizations for patients with cancer receiving chemotherapy who present to the ED. Methods: As part of a quality improvement initiative, we reviewed ED visits within 30-days of patients receiving intravenous chemotherapy at Massachusetts General Hospital from October 2017-January 2018. We used descriptive statistics to compare sociodemographic and clinical factors for hospitalized and non-hospitalized patients. We used logistic regression to explore variables independently associated with being hospitalized. We also compared death rates within 6 months between groups. Results: We identified 500 ED visits during our study period, which resulted in 350 (70.0%) hospitalizations. Hospitalized and non-hospitalized patients did not differ by age (mean 64.1 vs 63.4, P = 0.61), sex (48.9% vs 51.3% female, P = 0.61), or presence of metastatic disease (71.1% vs 68.7%, P = 0.59). Hospitalized patients were more likely to have gastrointestinal (25.7% vs 20.7%) and lung (14.0% vs 11.3%) cancer; less likely to have breast cancer (7.4% vs 16.7%, P &lt; 0.01). Hospitalized patients were more likely to come to the ED on a Thursday (15.7% vs 6.7%); less likely to come on a Wednesday (10.3% vs 19.3%, P &lt; 0.01). On logistic regression, factors associated with higher likelihood of being hospitalized included white race (OR = 1.84, P = 0.03), and presenting with fever/cold symptoms (OR = 2.64, P &lt; 0.01), fatigue (OR = 2.15, P = 0.04), or dyspnea (OR = 2.29, P = 0.04). Death rates within 6 months were higher for the hospitalized patients (50.0% vs 18.7%, P &lt; 0.01). Conclusions: Patients with cancer who visited the ED within 30-days of receiving intravenous chemotherapy often require hospitalization. We identified factors associated with higher likelihood of hospitalization, including patient characteristics, presenting symptoms, and the day of the week. Our findings should inform future efforts to enhance care delivery and outcomes for patients with cancer receiving chemotherapy.
Abstract 465: High Circulating Levels of 8-OHdG are an Independent Predictor of Subsequent MACE
Authors: Oxana Galenko, Serene A Kergaye, Stacey Knight, Joseph B Muhlestein, Jeffrey L Anderson, Kirk U Knowlton, John F Carlquist
Journal: Circulation Research (2019)

Objective: Oxidative stress is associated with several cardiovascular risk factors and cardiovascular disease. Damaged cells release cell-free DNA (cfDNA) into the circulation; oxidized cfDNA presence in the plasma indicates a pathological process in the context of oxidative stress. We hypothesized that biomarker of oxidative DNA damage 8-hydroxy- 2’deoxyguanosine (8-OHdG) may be associated with incident major adverse cardiovascular events (MACE). Methods: Plasma samples from 84 consenting patients undergoing coronary angiography at Intermountain Healthcare were obtained at the time of the procedure and tested for 8-OHdG by ELISA. Study endpoints were subsequent myocardial infarction (MI), stroke and all-cause death (determined by electronic medical records and death certificates) within median follow-up of 10 years (IQR: 8.8, 10.6). Cox-proportional hazard analysis was used for examining MACE rate association by quartile of 8-OHdG. Results: Mean 8-OHdG was significantly higher for individuals with a subsequent MACE vs those without (124.8 and 98.7 nM, respectively; p&lt;0.006, t-test). No other baseline demographic was significantly associated with 8-OHdG. MACE rates by 8-OHdG quartiles revealed a significant trend (p = 0.0346) (Figure). Hazard ratio increased by 1.653 for every 42 unit increase in 8-OHdG, p=0.006. Conclusion: High 8-OHdG plasma levels independently predict subsequent MACE. Whether 8-OHdG is contributes etiologically to event causation needs to be determined.
Abstract 759: Circulating Preoperative microRNA-29, Biomarkers of Collagen Synthesis, and Age Predictive of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting
Authors: Farhan Rizvi, Mahek Mirza, Susan Olet, Melissa Albrecht, Stacie Edwards, Larisa Emelyanova, David Kress, Gracious R Ross, Ekhson Holmuhamedov, A. Jamil Tajik, Bijoy K Khanderia, Arshad Jahangir
Journal: Circulation Research (2019)

Background: Postoperative atrial fibrillation (PoAF) is a common complication occurring in 35-50% patients within 2-3 days after cardiac surgery. Identification of patients, especially those with no prior history of atrial fibrillation before surgery, is a challenge. A pre-existing atrial substrate appears to be an important factor in the development of PoAF. The aim of this study was to assess the role of biomarkers in identifying patients at risk of PoAF in a pathophysiology-based risk predictive model by combining clinical and biochemical risk factors. Methods: Preoperative blood from patients undergoing cardiac surgery with no previous history of AF was assessed for circulating levels of biomarkers reflecting collagen synthesis/degradation and extracellular matrix remodeling using ELISA. Reverse transcriptase polymerase chain reaction assessed microRNA29 in the serum and correlated to extent of atrial fibrosis. Echocardiographic evaluation of LA mechanics was performed preoperatively using M-mode, 2D Doppler, and 3D Speckle tracking. Results: Out of 55 patients, 31 patients (56.4%) who developed PoAF after surgery during their hospital stay were older in age (70.0 ± 4.0 years vs.63.4±9.9; p&lt;0.01) with abnormal global longitudinal stain (6.9±0.69 vs.10.9±0.93, p=0.007), higher amino-terminal peptide procollagen III (PIIINP) levels (101.1±42.7 vs.36.6±20.0; p=0.043) with increased collagen to myocardial ratio (0.20±0.09 vs. 0.09±0.01, p= 0.026), and reduced preoperative circulating microRNA-29a, -29b and -29c levels. By combining the clinical risk factors, circulating biochemical and molecular biomarkers, we developed a model that identified PoAF patients (AUC=0.7987; 95% CI, 0.6174—0.98) with reduced preoperative atrial ejection fraction (32±2% vs. 42±2 %; p=0.01) as an independent risk factor for PoAF. Conclusion: Our study developed a noninvasive tool to identify those who are at risk for new-onset PoAF in patients with no previous history of AF when combining age, biomarkers of collagen synthesis and microRNA-29a.
Abstract 585: Role of Splice Variant Clic5B in Cardiac Mitochondrial Localization and Function
Authors: Devasena Ponnalagu, Ahmed T Hussain, Erhe Gao, Harpreet Singh
Journal: Circulation Research (2019)

Blocking chloride channels (Cl - ) with indanyloxyacetic acid (IAA-94) abrogated the cardio-protective effects of ischemic preconditioning (IPC) and increased myocardial infarction suggesting the possible contribution of IAA-94 sensitive Cl - channels in IPC mediated cardio-protection. Unlike cation channels, insights into the role of Cl - channels in cardioprotection is limited due to lack of information on their molecular identity. Chloride intracellular channel (CLIC) proteins are one of the known targets of IAA-94. They exist in both soluble and integral membrane form. Amongst the six known mammalian paralogs, CLIC1, CLIC4 and CLIC5 are most abundant in heart. Previously, we showed differential localization of CLIC4 and CLIC5 to outer and inner mitochondrial membrane respectively where as CLIC1 is present in the endoplasmic reticulum. Both CLIC4 and CLIC5 are important for mitochondrial functional integrity as well as cardioprotection from ischemia-reperfusion injury. Interestingly, none of the CLICs possesses conventional mitochondrial targeting sequence, which intrigued us to understand the mechanism of their localization to mitochondria. In this study we demonstrate that the mitochondrial localization of CLIC5 is related with the presence of splice variant CLIC5B (~50 kDa) in heart but not in lung lysates. Two different bands of CLIC5 at ~30 kDa (CLIC5A) and ~50 kDa, were observed in the cardiac mitochondrial lysates. Lung lysates showed the presence of only CLIC5A. In addition, mass spectrometric analysis revealed a peptide coverage of ~30% corresponding to CLIC5B at 50 kDa in heart but not in lung lysates further confirming its presence in heart. Moreover CLIC5 localized to mitochondria in p3 neonatal cardiomyocytes isolated from mouse but not in mouse lung epithelial (11 ± 2.1 %) cells which lacked CLIC5B indicating that the splice variant CLIC5B has a role in IMM localization. Interestingly, cardiac mitochondria from clic5 -/- mice exhibited increased ROS (p&lt; 0.05, n=3) production whereas the clic5 -/- lung mitochondria did not show any change, suggesting the role of CLIC5B in regulating the mitochondrial function as well. Our study establishes splice variation as a mechanism for targeting ion channels to mitochondria.
The Effect of JAK 1/2 Inhibitors on Outcomes of Allogeneic Stem Cell Transplantation for Patients with Myelofibrosis
Authors: Guido Lancman, Kathleen Miller, Shuli Li, Vincent T. Ho, Amir T. Fathi, Yi-Bin Chen, Alla Keyzner, Douglas Tremblay, Anita Geevarghese, Prapti Chatterjee, Ronald Hoffman, John Mascarenhas, Gabriela S. Hobbs
Journal: Blood (2018)
Abstract 282: Mitochondrial Complex I Induced Myocardial Stunning Following Cardiopulmonary Resuscitation
Authors: Lin Piao, Yonghu Fang, Robert B Hamanaka, Gökhan M Mutlu, Cameron Dezfulian, Stephen L Archer, Willard W Sharp
Journal: Circulation Research (2019)

Background: Cardiogenic shock following cardiopulmonary resuscitation (CPR) for sudden cardiac arrest is common, occurring even in the absence of acute coronary artery occlusion, and contributes to high rates of post-CPR mortality. The pathophysiology of this shock is unclear and effective therapies for improving clinical outcomes are lacking. Methods and Results: Using a murine model of asystolic cardiac arrest, we investigated the pathophysiology of post-CPR cardiogenic shock and discovered that duration of cardiac arrest (4, 8, 12 or 16-minute) prior to CPR determined post-resuscitation success rates, degree of neurological injury, and severity of myocardial dysfunction. Post-CPR cardiac dysfunction was not associated with myocardial necrosis, apoptosis, inflammation, or mitochondrial permeability transition pore opening and recovered within several days, indicative of myocardial stunning. Post-CPR myocardial stunning was associated with increases in ventricular and mitochondrial reactive oxygen species (ROS, P &lt;0.001 vs Sham, respectively). Seahorse micropolarimetry of isolated post-CPR cardiac mitochondria revealed decreased rates of maximal oxygen consumption rates (OCR) for both Complex I and Complex II vs controls ( P &lt;0.01 vs Sham, respectively), indicating inhibition of mitochondrial oxidative phosphorylation. Paradoxically, in the presence of ADP stimulated coupled respiration, post-CRP mitochondria demonstrated increased OCR ( P &lt;0.05 vs Sham) and increased rates of proton leak ( P &lt;0.05 vs Sham), suggesting Complex I as the site of ROS generation. These findings were not observed at complex II. S1QEL, a complex I-specific superoxide inhibitor, administered during CPR, decreased myocardial ROS generation while improving post-CPR myocardial function ( P &lt;0.01 vs CPR control), neurological injury ( P &lt;0.01 vs CPR control), and survival ( P &lt;0.01 vs CPR control). Conclusions: Our results demonstrate that cardiogenic shock following resuscitation from cardiac arrest is consistent with myocardial stunning mediated by mitochondrial complex I injury and ROS generation. Targeting this mechanism represents a novel and practical therapy for improving sudden cardiac arrest resuscitation outcomes.
Abstract 591: Improving Cardiovascular Health Through DNA Repair
Authors: Colin G Wu
Journal: Circulation Research (2019)

Accumulated DNA damage and oxidative stress play a critical role in the etiology of cardiovascular diseases. Malfunctions of human DNA repair proteins can lead to increased myocardial infarctions, ischemic heart disease, and congestive heart failure. The FANCJ helicase and the BRCA1 tumor suppressor are essential proteins that coordinate the repair of interstrand DNA crosslinks and double-stranded breaks in human cells. Their activities are especially needed in heart muscle, which undergoes tremendous physiological and chemical stress. Our limited understanding of how FANCJ and BRCA1 target damaged DNA structures remains a major barrier to research progress. As an independent investigator, my primary focus is to assess the impact of oxidative DNA damage on cardiovascular health through systematic dissection of the DNA repair pathways maintained by FANCJ and BRCA1. A detailed understanding of these molecular mechanisms would provide new diagnostic and therapeutic strategies to detect and to treat ischemic heart disease and congestive heart failure. Here, we have examined the DNA binding properties of FANCJ and BRCA1 using fluorescence spectroscopy and biolayer interferometry. We have also measured the viabilities of human cardiomyocytes and probed their sensitivity to reactive oxygen species by automated cell counting and single-cell electrophoresis. The DNA binding results, which describe precisely how FANCJ and BRCA1 organize onto damaged DNA sites, are compared with the cell-based analysis to correlate their DNA interaction patterns with cardioprotection. Our future work will utilize this platform to predict the risks of FANCJ and BRCA1 single-nucleotide polymorphisms that still have unknown cardiovascular effects.