tbuckley/cabot-search huggingface dataset:
Abstract 11714: Allogeneic Cardiosphere-Derived Cells Administered at the Time of Reperfusion Only Improve Ejection Fraction When Infused to Ischemic as well as Remote Myocardial Regions in Swine With Acute Myocardial Infarction
Authors: Gen Suzuki, Brian R Weil, Rebeccah F Young, James A Fallavollita, John M Canty
Journal: Circulation (2015)

Introduction: While intracoronary infusion of cardiosphere-derived cells (CDCs) to myocardial infarcts using the stop-flow technique reduces scar volume, ejection fraction (EF) remains unchanged. Hypothesis: We hypothesized that this may relate to ineffective treatment of myocyte loss in normally-perfused remote regions which could negatively impact EF. We therefore compared CDC infusion to the entire heart with conventional regional infusion to the infarct-related artery. Methods: Swine (n=24) chronically treated with cyclosporine (100 mg/day) underwent a 1-hour LAD occlusion and EF decreased from 60 ± 2% at baseline to 46 ± 2% after reperfusion (p&lt;0.05 vs. baseline). We infused either 10x10^6 intracoronary allogeneic CDCs via stop-flow infusion (regional LAD infusion), 20x10^6 intracoronary allogeneic CDCs to the entire heart under flow (global infusion) or vehicle 30 minutes after reperfusion. Four weeks later we assessed left ventricular function (echo), myocyte proliferation (Ki67), infarct size (TTC), myocyte nuclear density and cell size. Data were compared to vehicle. Results: Regional LAD infusion increased wall thickening and reduced scar volume but did not affect EF (Table). In contrast, global infusion increased EF despite an insignificant reduction in infarct volume. This was accompanied by 2-fold increases in myocyte proliferation (Ki67) in border and remote regions which did not change with regional LAD infusion. Global infusion increased myocyte nuclear density by 12% and decreased cell size by 9% while there were no significant changes after regional LAD infusion. Conclusion: Although regional LAD infusion reduces scar size and improves regional function, only global infusion improves EF since it effectively stimulates endogenous myocyte regeneration throughout the entire left ventricle. Thus, global infusion may more effectively prevent deleterious post-infarction remodeling than regional administration alone.
Hypomethylating agents in combination with venetoclax for acute myeloid leukemia: Update on clinical trial data and practical considerations for use
Authors: Matthew Mei, Ibrahim Aldoss, Guido Marcucci, Vinod Pullarkat
Journal: American Journal of Hematology (2018)

One of the most promising developments in therapy for acute myeloid leukemia (AML) in recent years has been the combination of hypomethylating agents (HMA, either decitabine or 5-azacytidine) with the Bcl-2 inhibitor venetoclax (VEN). Although both classes of drugs have single-agent activity in AML, the combination has resulted in high rates of complete remission (CR) both in the frontline and relapsed settings suggesting synergy between these two agents. Recent data have suggested that CR + CR with incomplete count recovery rate may exceed 70% for frontline VEN-HMA. Moreover, this activity has been observed across various genetic subtypes of AML including those known to have very poor response to conventional chemotherapy. Although VEN has only recently obtained FDA approval for treatment of AML, there has been increasing on and off-label use of this combination given its striking efficacy and excellent toxicity profile. In this article, we summarize the current available data on this combination and offer practical guidelines for management of patients receiving VEN-HMA. Our recommendations are based on protocol guidelines, published data from clinical trials as well as from analysis of real world evidence from patients treated with this combination.
Standardizing goals of care (GoC) documentation for new patients with metastatic disease.
Authors: Wajih Kidwai, Constance Engelking, Jennifer Pyle, Anne C. Chiang
Journal: Journal of Clinical Oncology (2018)

26 Background: Executing GoC discussions is an established national standard, underpins high quality patient-centered cancer care and ensures that patients participate actively in treatment decision-making. Capturing key aspects of those discussions in electronic documentation can be challenging when provider time is limited. This project sought to standardize workflow components to enable provider capacity to meet a GoC standard that ≥75% of patients presenting with metastatic cancer have a GoC discussion by their third visit as evidenced by retrievable documentation (EMR format and location). Methods: Baseline data describing provider: patient GoC interactions with eligible patients was obtained and presented. Providers reached consensus on a consistent timing, location and content for electronic GoC documentation. Patient assessment parameters for identifying patients needing GoC discussions were generated, a procedure outlining documentation expectations and facilitative tools were developed. Clinicians were educated on their roles in the process. A variety of quality improvement tools were utilized in project execution (e.g. focus groups, process mapping, cause-effect diagraming, pareto and control charting). Results: See table. Conclusions: Despite time constraints in a busy practice, the ≥75% target set for retrievable GoC documentation was exceeded within the 9-month project timeframe. Providers improved their documentation with familiarity and experience over time. Compliance with documentation location and use of smart phrases were not fully realized, likely due to the short timeframe for adoption of all elements of project aims. Continued improvement is expected as providers become more comfortable with the process and additional facilitative strategies are further integrated including expanding nursing assessment of patients' GoC needs, dedicating time in scheduling templates, Epic alert builds and utilizing Palliative Care Team assist for patients deemed uncomfortable with GoC discussions.[Table: see text]
Abstract #3872: NGAL mediates erlotinib resistance in NSCLC
Authors: Xiaoyan Cui, Li Zhu, Kostyantyn Krysan, Jie Luo, Sherven Sharma, Steven Dubinett
Journal: Cancer Research (2009)

To study erlotinib resistance in non-small cell lung cancer (NSCLC), we developed several erlotinib resistant cell lines by growing the initially moderately sensitive cells in the presence of increasing concentrations of erlotinib. Gene expression profiling (Affymetrix U133 Plus 2.0 Array) analysis indicates neutrophil gelatinase associated lipocalin (NGAL, also named lipocalin-2), is upregulated more than 200 fold in resistant cells. Western blot confirmed this result. To study the potential role of NGAL in erlotinib resistance, we established two stable NGAL overexpressing NSCLC cell lines, H441NGAL and H3255NGAL. Both cell lines were more resistant to erlotinib-induced apoptosis than control cell lines. The proapoptotic protein Bim was decreased and ERK1/2 phosphorylation was increased in both NGAL overexpressing cell lines. Knockdown of Bim expression by siRNA decreased apoptosis sensitivity, suggesting NGAL-mediated erlotinib resistance was Bim-dependent. Erlotinib treatment inhibited ERK1/2 phosphorylation and induced Bim expression, however, this induction was attenuated in both NGAL overexpressing cell lines. Studies using a proteosome inhibitor suggest that NGAL may promote Bim degradation via the ubiquitin-proteosome pathway via increasing ERK1/2 phosphorylation. In SCID mice, tumors derived from H3255NGAL cells are more resistant to erlotinib-induced growth inhibition compared to those derived from control cells. Compared to patients responding to therapy, serum NGAL levels in patients with late stage NSCLC receiving erlotinib treatment in progressive disease were higher. Our results suggest that NGAL could confer erlotinib resistance by decreasing Bim expression and increasing apoptosis resistance in NSCLC.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3872.
Rethinking community based strategies to tackle health inequities in South Asia
Authors: Zulfiqar A Bhutta, Abhay Bang, Kaosar Afsana, Bishal Gyawali, Shafiq Mirzazada, Renuka Jayatissa
Journal: BMJ (2018)

A long term strategy is vital to build on the impact of community health workers in achieving universal health coverage, say Zulfiqar Bhutta and colleagues
T-cell functionality testing is highly relevant to developing novel immuno-tracers monitoring T cells in the context of immunotherapies and revealed CD7 as an attractive target
Authors: Kristine E. Mayer, Sabine Mall, Nahid Yusufi, Dario Gosmann, Katja Steiger, Lisa Russelli, Henrique de Oliviera Bianchi, Stefan Audehm, Ricarda Wagner, Eva Bräunlein, Anja Stelzl, Florian Bassermann, Wilko Weichert, Wolfgang Weber, Markus Schwaiger, Calogero D'Alessandria, Angela M. Krackhardt
Journal: Theranostics (2018)

Cancer immunotherapy has proven high efficacy in treating diverse cancer entities by immune checkpoint modulation and adoptive T-cell transfer.However, patterns of treatment response differ substantially from conventional therapies, and reliable surrogate markers are missing for early detection of responders versus non-responders.Current imaging techniques using 18 F-fluorodeoxyglucose-positron-emmission-tomograpy ( 18 F-FDG-PET) cannot discriminate, at early treatment times, between tumor progression and inflammation.Therefore, direct imaging of T cells at the tumor site represents a highly attractive tool to evaluate effective tumor rejection or evasion.Moreover, such markers may be suitable for theranostic imaging.Methods: We mainly investigated the potential of two novel pan T-cell markers, CD2 and CD7, for T-cell tracking by immuno-PET imaging.Respective antibody-and F(ab´) 2 fragment-based tracers were produced and characterized, focusing on functional in vitro and in vivo T-cell analyses to exclude any impact of T-cell targeting on cell survival and antitumor efficacy.Results: T cells incubated with anti-CD2 and anti-CD7 F(ab´) 2 showed no major modulation of functionality in vitro, and PET imaging provided a distinct and strong signal at the tumor site using the respective zirconium-89-labeled radiotracers.However, while T-cell tracking by anti-CD7 F(ab´) 2 had no long-term impact on T-cell functionality in vivo, anti-CD2 F(ab´) 2 caused severe T-cell depletion and failure of tumor rejection. Conclusion:This study stresses the importance of extended functional T-cell assays for T-cell tracer development in cancer immunotherapy imaging and proposes CD7 as a highly suitable target for T-cell immuno-PET imaging.
Does increasing insurance improve outcomes for U.S. cancer patients?
Authors: J. K. Smith, J. E. Carroll, S. Ng, S. A. Shah, T. P. McDade, J. F. Tseng
Journal: Journal of Clinical Oncology (2010)

6015 Background: While debate continues on U.S. health care and insurance reform, there is lack of data on the impact of insurance when confronted with cancer. We examined insurance coverage and cancer mortality state-by-state. Methods: The U.S. Census Bureau Current Population Survey (2002-2004) was used for rates of uninsurance. Data were compared to cancer incidence and mortality from National Cancer Institute State Cancer Profiles (2002-2006). Individual cancer lethality rates were calculated. Rates of % uninsured and cancer lethality were evaluated. Results: U.S. uninsurance rate 2002-2004 was 15.5%. Examining the three states with significant decreases in uninsurance, the best insurance trend state demonstrated lower lethality rates than the U.S. averages across all identified cancers. Higher uninsurance was associated with higher than U.S. average cancer lethality rates, whereas better insured states were more likely to have lower than U.S. average rates (see Table). Conclusions: At the state level, insurance coverage correlated with improved cancer outcomes. Future work should examine these associations within individual communities and how best to surmount any barriers to cancer care in those communities. Cancer lethality among states with lowest and highest rates of uninsurance US MN HI IA VT RI LA NV OK NM TX % Uninsured 15.5 8.5 9.9 10.1 10.5 10.5 18.8 19.1 19.2 21.4 25.1 Lethality (%) by cancer site Pancreas 93.9 100 84.3 93.6 76.6 92.0 90.2 86.4 98.1 96.1 96.2 Esophagus 89.8 88.2 74.5 94.5 75.0 87.0 84.0 95.6 85.1 100 86.4 Liver/bile duct 88.3 95.6 69.5 97.6 100 85.1 98.4 87.1 75.4 80.3 82.4 Lung/bronchus 77.4 81.0 75.2 73.8 63.3 71.8 79.6 76.9 78.7 80.7 79.8 Ovary 69.1 67.5 73.5 65.9 58.3 73.4 73.1 64.0 64.0 78.0 69.2 Leukemia 61.5 48.3 51.5 58.1 69.0 53.7 67.6 59.3 53.0 50.9 53.5 Colon/rectum 36.5 33.2 29.5 34.3 34.0 28.9 37.3 37.5 34.8 38.6 38.9 Non-Hodgkin lymphoma 35.8 33.3 36.7 35.3 29.0 34.0 37.7 37.4 36.4 43.5 35.6 Breast 19.6 16.5 16.8 18.8 16.1 16.3 22.9 18.7 21.0 20.2 20.2 Prostate 15.5 12.1 10.1 18.1 13.5 16.3 17.5 17.0 14.6 19.2 16.0 Melanoma 14.8 11.1 9.4 13.1 10.8 15.3 15.8 18.3 17.8 21.8 19.4 Thyroid 4.6 4.8 ≤15 cases 7.2 ≤15 cases ≤15 cases 5.9 ≤15 cases 6.6 ≤15 cases 4.0 Abbreviations: US, United States; MN, Minnesota; HI, Hawaii; IA, Iowa; VT, Vermont; RI, Rhode Island; LA, Louisiana; NV, Nevada; OK, Oklahoma; NM, New Mexico; TX, Texas. No significant financial relationships to disclose.
Integrating the ENABLE early palliative care approach in community cancer centers: Results of an implementation trial.
Authors: Marie Bakitas, J Nicholas Dionne-Odom, Maria Pisu, Andres Azuero, Dilip Sankar Babu, Lucy Jean Gansauer, James D. Bearden, Keith M Swetz, Leigh Minchew, Margaret Murray Sullivan, Rachel Wells, Richard A. Taylor, Yasemin E. Turkman, Thomas Ramsey, Lisa Zubkoff
Journal: Journal of Clinical Oncology (2018)

114 Background: Despite national guidelines recommending early palliative care (EPC) for individuals newly-diagnosed with metastatic cancer, it is rarely available in rural community cancer centers serving underserved populations. We conducted the first implementation trial of EPC in rural cancer centers using the evidence-based ENABLE (Educate, Nurture, Advise, Before Life Ends) model of early, concurrent oncology palliative care. Methods: Mixed methods case study of a 4-year American Cancer Society-funded 4-site, implementation trial using a virtual learning collaborative in AL and SC. Guided by the RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) framework, we gathered qualitative and quantitative data via monthly reports and yearly in-person site visits using: 1) a RE-AIM Self-Assessment Tool completed by site staff to measure reach, adoption, implementation, and maintenance; 2) EPC General Organizational Index (GOI) to measure capacity for EPC services and implementation progress; and 3) field notes from site interviews and final reports. Results: Across the 4 sites, 62 patients (range: 4–31; mean: 15) and 46 caregivers (range: 2–22; mean: 12) participated. Baseline patient characteristics included: mean age of 58, 70% female, 17% Black or minority, 57% some college or college, 49% rural dwelling, and 57% non-gynecologic cancer. Sites enrolled at least 58% of the patients they planned to enroll (range: 58%–100%; average: 84%), of which 44% received 100% of ENABLE content and nearly 60% received two-thirds. Reasons for not completing all six sessions included death, unrecorded contacts, or lost to follow up. Longitudinal GOI scores indicated a trend of improved capacity for EPC services at three of the four sites. Qualitative data from site lead interviews revealed administrative (presence or lack of palliative ‘champions’), clinical (having adequate training), and economic (reimbursement) implementation barriers and facilitators. Conclusions: This pilot implementation study demonstrated feasibility and areas to enhance implementation in a larger comparative effectiveness trial to enhance scaling and spreading EPC in community practices.
Harbingers of Mental Disease—Infections Associated With an Increased Risk for Neuropsychiatric Illness in Children
Authors: Viviane Labrie, Lena Brundin
Journal: JAMA Psychiatry (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Statistical compared to clinical significance and the risk of misattribution
Authors: Magnus Ekström, Miriam J. Johnson, David C. Currow
Journal: European Respiratory Journal (2018)

<b>Observational analyses of putative drug effects, including a recent on antidepressants and increased mortality in COPD, may be biased, should be interpreted sceptically and often need to be confirmed by randomised data to change practice.</b>http://ow.ly/oh5030m9Q9I
The Hands of an Angel
Authors: Richard B. Weinberg
Journal: Annals of Internal Medicine (2018)

On Being a Doctor4 December 2018The Hands of an AngelRichard B. Weinberg, MDRichard B. Weinberg, MDWake Forest School of Medicine, Winston Salem, North Carolina (R.B.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-2379 Audio Reading - “The Hands of an Angel” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Hands of an Angel," by R.B. Weinberg. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail We huddled together on opposite sides of the nurses' station like sweaty preadolescents at their first middle school dance: interns on one side, newly graduated nurses on the other. Mrs. Lincoln, the veteran head nurse of 3 West, stood before us, lecturing us on hospital policies. Her words sailed inaudibly over me, muted by my racing pulse and uncontrollable anxiety—I had never been as scared as I was on that first day of my internship. Scanning the assembled faces, I saw that I was not alone: Everyone bore the same tight, teeth-gritted grimace of apprehension and fear … except her.... Author, Article, and Disclosure InformationAffiliations: Wake Forest School of Medicine, Winston Salem, North Carolina (R.B.W.)Corresponding Author: Richard B. Weinberg, MD, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27104; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “The Hands of an Angel” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "The Hands of an Angel," by R.B. Weinberg. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: 815-816KeywordsComaFearNauseaNursesPostural controlShockSleepStrokeThoraxTouch ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges
Authors: Luis M. Seijo, Nir Peled, Daniel Ajona, Mattia Boeri, John K. Field, Gabriella Sozzi, Ruben Pio, Javier J. Zulueta, Avrum Spira, Pierre P. Massion, Peter J. Mazzone, Luis M. Montuenga
Journal: Journal of Thoracic Oncology (2018)
An ATF6-tPA pathway in hepatocytes contributes to systemic fibrinolysis and is repressed by DACH1
Authors: Ze Zheng, Lalitha Nayak, Wei Wang, Arif Yurdagul, Xiaobo Wang, Bishuang Cai, Stephanie Lapping, Lale Ozcan, Rajasekhar Ramakrishnan, Richard G. Pestell, Mukesh K. Jain, Ira Tabas
Journal: Blood (2018)

Tissue-type plasminogen activator (tPA) is a major mediator of fibrinolysis and, thereby, prevents excessive coagulation without compromising hemostasis. Studies on tPA regulation have focused on its acute local release by vascular cells in response to injury or other stimuli. However, very little is known about sources, regulation, and fibrinolytic function of noninjury-induced systemic plasma tPA. We explore the role and regulation of hepatocyte-derived tPA as a source of basal plasma tPA activity and as a contributor to fibrinolysis after vascular injury. We show that hepatocyte tPA is downregulated by a pathway in which the corepressor DACH1 represses ATF6, which is an inducer of the tPA gene Plat Hepatocyte-DACH1-knockout mice show increases in liver Plat, circulating tPA, fibrinolytic activity, bleeding time, and time to thrombosis, which are reversed by silencing hepatocyte Plat Conversely, hepatocyte-ATF6-knockout mice show decreases in these parameters. The inverse correlation between DACH1 and ATF6/PLAT is conserved in human liver. These findings reveal a regulated pathway in hepatocytes that contributes to basal circulating levels of tPA and to fibrinolysis after vascular injury.
Engineered RNase P Ribozymes Effectively Inhibit the Infection of Murine Cytomegalovirus in Animals
Authors: Wei Li, Yujun Liu, Yuanyuan Wang, Ruilin Li, Phong Trang, Wei Tang, Zhu Yang, Yu Wang, Xu Sun, Xiwen Xing, Sangwei Lu, Fenyong Liu
Journal: Theranostics (2018)

Rationales: Gene-targeting ribozymes represent promising nucleic acid-based gene interference agents for therapeutic application.We previously used an in vitro selection procedure to engineer novel RNase P-based ribozyme variants with enhanced targeting activity.However, it has not been reported whether these ribozyme variants also exhibit improved activity in blocking gene expression in animals.Methods and Results: In this report, R388-AS, a new engineered ribozyme variant, was designed to target the mRNA of assemblin (AS) of murine cytomegalovirus (MCMV), which is essential for viral progeny production.Variant R338-AS cleaved AS mRNA sequence in vitro at least 200 times more efficiently than ribozyme M1-AS, which originated from the wild type RNase P catalytic RNA sequence.In cultured MCMV-infected cells, R338-AS exhibited better antiviral activity than M1-AS and decreased viral AS expression by 98-99% and virus production by 15,000 fold.In MCMV-infected mice, R388-AS was more active in inhibiting AS expression, blocking viral replication, and improving animal survival than M1-AS.Conclusions: Our results provide the first direct evidence that novel engineered RNase P ribozyme variants with more active catalytic activity in vitro are also more effective in inhibiting viral gene expression in animals.Moreover, our studies imply the potential of engineering novel RNase P ribozyme variants with unique mutations to improve ribozyme activity for therapeutic application.