tbuckley/cabot-search huggingface dataset:
Abstract 236: Biphasic Reprogramming of Ventricular Cardiomyocytes to Pacemaker Cells by Tbx18
Authors: Jinqi Fan, Natasha Fernandez, Hee Cheol Cho
Journal: Circulation Research (2019)

Background: We have previously demonstrated that an embryonic transcription factor, TBX18, suffices to reprogram postnatal ventricular cardiomyocytes to induced pacemaker cells. Here, we sought to gain finer understanding of the reprogramming process by investigating genotype/phenotype of the de novo pacemaker cells in multiple temporal domains. Methods: TBX18-induced pacemaker cells (TBX18-iPMs) were created in vitro by somatic gene transfer of Adeno-TBX18 into neonatal rat ventricular myocytes (NRVMs). Control ventricular myocytes were transduced with Adeno- GFP. To investigate in vivo reprogramming, we delivered AAV9-TBX18 via tail vein of Hcn4(+/eGFP) heterozygous transgenic mice, which expresses eGFP under the Hcn4 promoter, so as to lineage-trace de novo pacemaker cells in the ventricular myocardium. Results: The automaticity of TBX18-iPMs was higher than that of GFP-NRVMs during D1-D3, decreased after D3 and rebound by D14. Monolayers of the iPMs revealed multiple foci of spontaneous field potentials with lower spike amplitude, spike slope, and conduction velocity, demonstrating phenotypic reprogramming to the iPMs by D14. RNAseq and qPCR revealed two distinct phases of reprogramming; an early phase that showed loss of expression of ventricular myocyte-related gene program and a late phase that showed gain of expression of nodal gene program which plateaued by D14. For example, Hcn4 gene expression began increasing during week 1 and continued the pattern during week 2. By week 3, Hcn4-positive TBX18-iPMs appeared in clusters of NRVM monolayers while GFP-NRVMs were spread evenly throughout the monolayers. We lineage-traced de novo, TBX18-reprogrammed pacemaker cells in vivo by delivering AAV9-TBX18 via tail-vein of Hcn4(+/eGFP) mice. In line with our in vitro data, in vivo pacemaker cell lineage tracing experiments indicated a progressive loss of ventricular gene program followed by gain of nodal gene program. Conclusions: Our data indicate that TBX18-induced reprogramming of ventricular myocytes to nodal pacemaker cells undergoes progressive changes in gene expression shedding ventricular gene/phenotype first, and then gaining nodal pacemaker genotype/phenotype, establishing fully functional nodal pacemaker by D14.
Technology-Enabled Clinical Trials
Authors: Guillaume Marquis-Gravel, Matthew T. Roe, Mintu P. Turakhia, William Boden, Robert Temple, Abhinav Sharma, Boaz Hirshberg, Paul Slater, Noah Craft, Norman Stockbridge, Bryan McDowell, Joanne Waldstreicher, Ariel Bourla, Sameer Bansilal, Jennifer L. Wong, Claire Meunier, Helina Kassahun, Philip Coran, Lauren Bataille, Bray Patrick-Lake, Brad Hirsch, John Reites, Rajesh Mehta, Evan D. Muse, Karen J. Chandross, Jonathan C. Silverstein, Christina Silcox, J. Marc Overhage, Robert M. Califf, Eric D. Peterson
Journal: Circulation (2019)

The complexity and costs associated with traditional randomized, controlled trials have increased exponentially over time, and now threaten to stifle the development of new drugs and devices. Nevertheless, the growing use of electronic health records, mobile applications, and wearable devices offers significant promise for transforming clinical trials, making them more pragmatic and efficient. However, many challenges must be overcome before these innovations can be implemented routinely in randomized, controlled trial operations. In October of 2018, a diverse stakeholder group convened in Washington, DC, to examine how electronic health record, mobile, and wearable technologies could be applied to clinical trials. The group specifically examined how these technologies might streamline the execution of clinical trial components, delineated innovative trial designs facilitated by technological developments, identified barriers to implementation, and determined the optimal frameworks needed for regulatory oversight. The group concluded that the application of novel technologies to clinical trials provided enormous potential, yet these changes needed to be iterative and facilitated by continuous learning and pilot studies.
Is CRP-guided antibiotic treatment a safe way to reduce antibiotic use in severe hospitalised patients with exacerbations of COPD?
Authors: Marc Miravitlles, Carl Llor, Lars Bjerrum, Sanjay Sethi, Antonio Anzueto
Journal: European Respiratory Journal (2019)

We read with great interest the well-conducted clinical trial on C-reactive protein (CRP)-guided antibiotic treatment in admitted patients with acute exacerbations of COPD by Prins et al. [1]. This is a study showing that the use of CRP can potentially assist clinicians in making more prudent use of antibiotics in patients with severe exacerbations, as has also been found in the primary care setting [2]. One of the striking results is, however, the disturbingly high rate of treatment failure observed of approximately 24% at 10 days and 45% at 30 days, as pointed out in the accompanying editorial [3], and consistent with this high rate of treatment failure is a remarkably short time to next exacerbation of less than 1 month [1]. Since the percentage of patients treated with antibiotics in both study groups was very low (31% and 46%), it would be necessary to rule out that the reduction in the use of antibiotics is not responsible for an increase in clinical failures in this population with severe exacerbations of COPD. For comparison, a recent study using CRP to guide antibiotic use in much milder COPD patients in an ambulatory setting resulted in 57% of patients treated with antibiotics [4], in contrast to the 31% antibiotic prescription in CRP guided therapy in severe hospitalised patients in the study by Prins et al. [1]. A reduction in antibiotic use to treat COPD must be safe for the patient <http://bit.ly/2GxGpTO>
RhoA Gtpase Regulates Erythroblast Cytokinesis and Enucleation By Dynamic Coordination Of The Microtubule-Actomyosin Machineries For Successful Abscission
Authors: Diamantis G. Konstantinidis, Suvarnamala Pushkaran, Katie M. Giger, Ping Zhou, Paul R. Andreassen, Ursula Klingmuller, James Palis, Yi Zheng, Theodosia A. Kalfa
Journal: Blood (2013)
Successful Engraftment In Children With Severe Aplastic Anemia After Transplantation Of HLA-Identical Hematopoietic Donor Cells With Shorter Telomere Length
Authors: Abdulrahman Alsultan, Gabriela M. Baerlocher, Elisabeth Oppliger Leibundgut, Sameera AlAfghani, Reem Al-Sudairy, Mohammed Al Balwi, Mohammed Jarrar
Journal: Blood (2013)
Polyoma (BK) Viruria Prior to Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) from Donors Other Than Matched Siblings: A Prospective Evaluation of Hemorrhagic Cystitis (HC) Incidence
Authors: Leandro de Padua silva, Poliana Patah, Rima M. Saliba, Nicholas A. Szewczyk, Lisa Gilman, Alison Gulbis, Joyce Neumann, Julia Walker, Demetrios Petropoulos, Rocco LaSala, Kashif Ali Shaz Mir, Yago Nieto, Issa Khouri, Sergio Giralt, Richard E. Champlin, Marcos De Lima
Journal: Blood (2008)
Phase 2 Study of 5 Days Azacytidine Priming Prior to Fludarabine, Cytarabine and G-CSF Combination for Patients with Relapsed or Refractory AML
Authors: Ibraheem H. Motabi, Shahid Iqbal, Syed Ziauddin A. Zaidi, Belal Albtoosh, Nawal Faiez Alshehry, Mubarak S. AlGhamdi, Imran Khan Tailor, Syed Altaf
Journal: Blood (2018)
Ovarian metastases in colorectal carcinoma.
Authors: Idris Yucel, Dilek Erdem, Bahiddin Yilmaz, Guzin Gonullu
Journal: Journal of Clinical Oncology (2013)

e14697 Background: 5-30 % of all ovarian tumors are metastatic and only 3-14 % of them derive from gastrointestinal tract. The aim of this study is to determine the rate of colorectal cancer patients with ovarian metastases and also to identify the features in the management of these patients. Methods: 972 colorectal cancer patients admitted to our clinic between 01/2001 and 12/2011 were included in the study. Among these patients, only 9 had ovarian metastases. Age, menopausal status, initial symptom, operation status, localisation of colorectal tumor, stage at diagnosis, tumor grade, histopathological type, colorectal tumor-ovarian metastases interval, having synchronous or metachronous metastases, the place of metastases and concurrent metastatic disease were evaluated. SPSS 16 is used. Results: Mean age of patients was 45 years (range between 21-72 years). 66.7 % had premenopausal state. 55 % of them had right colon tumor. 5 patients had stage IV disease. 5 patients had synchronous metastases (55 %). Colorectal cancer-ovarian metastases interval was 6-49 months in the patients with metachronous metastases. Among patients; 5 had right and 1 had left ovarian metastases and 3 had metastases to both ovaries. 2 of 3 bilateral ovarian metastases were derived from right-sided tumors (66.6 %). 7 patients also had metastases to other different parts and most of those had peritoneal involvement (85.7 %). PFS was between 2 and 27 months. At the time of ovarian metastases, 7 patients had high CA 125 levels and 3 had high CEA levels. All patients with high levels of CA 125 during diagnosis continued to have high levels of CA 125 with ovarian metastases. Conclusions: Premenopausal patients seem to have higher risk of ovarian metastases. This study support that examining CA 125 levels in colorectal cancer patients who have abnormal findings in the gynecological examination preoperatively may help not to miss synchronous ovarian metastases.The finding of ovarian metastases should make consideration that the disease is disseminated. Ovaries should be examined preoperatively and it should be kept in mind that CA 125 levels may be a valuable marker in this setting.
Efficacy and Safety of Micafungin for Prophylaxis of Invasive Fungal Infections in Patients Undergoing Haplo-Identical Hematopoietic Stem Cell Transplant
Authors: Jean El-Cheikh, Geoffroy Venton, Roberto Crocchiolo, Sabine Furst, Catherine Faucher, Angela Granata, Claire Oudin, Reda Bouabdallah, Norbert Vey, Segolene Duran, Pierre Berger, Christian Chabannon, Didier Blaise
Journal: Blood (2012)
Turning influenza vaccinology on its head to reveal the stalk
Authors: Sophie A Valkenburg, Benjamin J Cowling
Journal: The Lancet Infectious Diseases (2019)

Inactivated influenza virus vaccines (IIVs) have been in use for more than 70 years with no major changes in the underlying technology. Limitations of these vaccines include the long production cycle, which requires strain selection well in advance of their use; provision of only moderate protection when vaccine strains match circulating strains; protection that wanes quickly; potential issues with repeated annual immunisation, such as reduced haemagglutination-inhibition boosting and protection from infection; and no protection against novel outbreak or pandemic strains.
Donor Lymphocyte Infusion from G-CSF-Primed, Unmanipulated Whole Blood Is Safe and Improves Chimerism in HLA-Matched and Haploidentical Transplantation
Authors: Andrés Gómez-De León, Perla R Colunga Pedraza, Diana E Garcia-Camarillo, Roberto I. Vázquez-Garza, Paola Santana-Hernandez, Cesar Homero Gutierrez Aguirre, Olga Cantu Rodriguez, David Gomez-Almaguer
Journal: Blood (2018)
Abstract 704: Profiling Differential Response to Myocardial Infarction by Single Cell Analysis of the Cardiac Interstitium
Authors: Elvira Forte
Journal: Circulation Research (2019)

Myocardial infarction (MI) is one of the main causes of mortality in Western Countries. The non-regenerative adult mammalian heart responds to injury with the formation of a scar. The outcome of repair is highly dependent on interstitial cells and on the delicate interplay between the inflammatory response and fibrosis, which leads to adverse ventricular remodeling and heart failure or cardiac rupture in the early phase post-injury. Our data show that inbred mice strains have different reliance to MI, suggesting differences in the cellular response to the injury. To profile the dynamic response of cardiac interstitial cells to MI and their embryological origin, we performed unbiased scRNAseq analysis of cardiac interstitial cells at homeostasis and 1, 3, 5, 7, 14, 28 days post-injury from transgenic mice on C57bl/6j background (B6), expressing ZsGreen under the control of the epicardial marker Wt1 ( Wt1 Cre ;RosaZsgreen f/+ ) . About 38,600 cells were captured using the 10xChromium technology and we distinguished 16 main cell populations that evolved over time. By high resolution sub-clustering of stromal cells, 7 main subpopulations were identified. Of these, one was endocardial derived and present at all time points, the others were epicardial derived (ZsGreen+) and included 3 populations of fibroblasts present at different frequencies at all time points, a transient population of immune-response activating fibroblasts (IR) prevailing at day1 and preceding the appearance of myofibroblasts between day 3 and 7 and matrifibrocytes prevalent at day 14 and day 28. To determine the role of cell composition in different reparative outcomes, we compared the data on the C57BL/6J background with 129S1/SvlmJ (129), the inbred strain presenting the highest frequency of cardiac rupture (70%) among the 9 tested. We observed increased number of activated IR and myofibroblasts in 129 3 days post-MI. 129 also showed higher level of collagens, chemokines, fibrin deposition and acute phase response genes. The hyperactivation of myofibroblasts was possibly mediated by the enhanced responsiveness to the Renin-Angiotensin System, currently one of the main targets of clinical therapies.
Coordination of Pro- and Anti-Inflammatory Signals Determine Human Hematopoietic Stem and Progenitor Cell Expansion
Authors: Jalila Chagraoui, Elisa Tomellini, Leo Aubert, Iman Fares, Jean-Francois Spinella, Simon Girard, Nadine Mayotte, Philippe P Roux, Guy Sauvageau
Journal: Blood (2018)
Pharmacist-driven oral oncolytic medication education and consent.
Authors: Bernard Tawfik, Harmony Bowles, Zoneddy R. Dayao, Richard C. Lauer, Janet Abernathy
Journal: Journal of Clinical Oncology (2019)

44 Background: The number and type of oral oncolytic therapy in oncology is expanding rapidly. Oral oncolytics have serious side effect potential and patient education has been shown to reduce adverse events. Pharmacist driven interventions have been shown to safety and adherence. The University of New Mexico Comprehensive Cancer Center (UNM CCC) initiated and then improved upon a pharmacist driven patient education and consent process for oral oncolytic therapy. Methods: A pharmacist driven education and consent process was initiated at UNM CCC and monitored from August 2016 to October 2018. The intervention initially used a message generated by an order in the Electronic Medical Record (EMR) to alert the pharmacist of new oral oncolytic prescriptions. Initial uptake by providers was low so education regarding this order was presented to providers. Outpatient pharmacy staff were instructed not to release first fill oral oncolytic prescriptions without notifying the pharmacist educator. Lastly, hematology and oncology fellows notified the pharmacist educator of patients discharged directly from the hospital with a new oncolytic prescription. The metric measured was the percent of patients on oral oncolytic therapy who were educated and consented by the pharmacist for oral oncolytic medications filled at UNM CCC. Statistical analysis included run charts with 95% Confidence Intervals and t-tests with two tails, assuming unequal variation between groups and an alpha of 0.05. Results: The initial monthly education and consent rate was 17.9% followed by 45.5% the following month. This quickly grew to an average of 87.0% (95% CI 55.7-118.2) for the subsequent 15 months which achieved control. Additional changes were made as part of the PDSA cycle which increased the education rate to 95.7% (95% CI 84.4-107.1). These two periods were statistically significantly different (p = 0.0025). Conclusions: A pharmacist driven program for education and consent upon initiation of oral oncolytics is possible and can successfully educate the majority of patients. Future expansions of this program will include ensuring patient adherence and educating patients who fill oral oncolytics outside UNM CCC.
Retrospective Analysis of Outcomes in Acute Myeloid Leukemia (AML) Patients Exposed to Intravenous Contrast Prior to Stem Cell Transplantation
Authors: Gayathri Ravi, Yazan Abou-Ismail, Margaret Rothgery, Anjali Shekar, Sophie Golec, Marcos de Lima, Ben Tomlinson
Journal: Blood (2018)
Is the Patient Cured?
Authors: Harry B. Burke, Scott Kopetz
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
FOLFOXIRI Plus Panitumumab As First-Line Treatment of <i>RAS</i> Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109)
Authors: Dominik P. Modest, Uwe M. Martens, Jorge Riera-Knorrenschild, Jobst Greeve, Axel Florschütz, Swen Wessendorf, Thomas Ettrich, Stephan Kanzler, Dominik Nörenberg, Jens Ricke, Max Seidensticker, Swantje Held, Petra Buechner-Steudel, Jens Atzpodien, Volker Heinemann, Thomas Seufferlein, Andrea Tannapfel, Anke C. Reinacher-Schick, Michael Geissler
Journal: Journal of Clinical Oncology (2019)

This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer.The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival.A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12).The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.
Association of Bulimia Nervosa With Long-term Risk of Cardiovascular Disease and Mortality Among Women
Authors: Rasmi M. Tith, Gilles Paradis, Brian J. Potter, Nancy Low, Jessica Healy-Profitós, Siyi He, Nathalie Auger
Journal: JAMA Psychiatry (2019)

Bulimia nervosa is associated with short-term cardiovascular complications in women, but its long-term consequences on cardiovascular health are unknown.To study the association of bulimia nervosa with the long-term risk of cardiovascular disease and mortality in women.In this longitudinal cohort study, 416 709 women hospitalized in Quebec, Canada, including women hospitalized for bulimia nervosa and those for pregnancy-related events as a comparison group, were followed up for 12 years from 2006 to 2018 to identify incidences of cardiovascular disease and death.At least 1 hospitalization for bulimia nervosa.The study participants were followed up to identify future incidences of cardiovascular disease and deaths. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs to assess the association of bulimia nervosa with future outcomes after adjustment for patient characteristics.The study population comprised 818 women who were hospitalized for bulimia nervosa (mean [SD] age, 28.3 [13.4] years) and 415 891 hospitalized for pregnancy-related events (mean [SD] age, 28.3 [5.4] years). Patients were followed up for a total of 2 957 677 person-years. The women hospitalized for bulimia nervosa had a greater incidence of cardiovascular disease compared with those hospitalized for pregnancy-related events (10.34 [95% CI, 7.77-13.76] vs 1.02 [95% CI, 0.99-1.06] per 1000 person-years). Incidence of future cardiovascular disease was even higher for women with 3 or more bulimia admissions (25.13 [95% CI, 13.52-46.70] per 1000 person-years). Women hospitalized for bulimia nervosa had 4.25 (95% CI, 2.98-6.07) times the risk of any cardiovascular disease and 4.72 (95% CI, 2.05-10.84) times the risk of death compared with women hospitalized for pregnancy-related events. Bulimia nervosa was found to be associated with ischemic heart disease (HR, 6.63; 95% CI, 3.34-13.13), atherosclerosis (HR, 6.94; 95% CI, 3.08-15.66), and cardiac conduction defects (HR, 2.99; 95% CI, 1.57-5.71). Bulimia was also associated with 21.93 (95% CI, 9.29-51.74) times the risk of myocardial infarction at 2 years of follow-up and 14.13 (95% CI, 6.02-33.18) times the risk at 5 years of follow-up.This study's findings suggest that bulimia nervosa may be associated with the long-term risk of any cardiovascular disease, such as ischemic cardiac events and conduction disorders, as well as with death among women. The findings also suggest that women with a history of bulimia nervosa should be screened regularly for ischemic cardiovascular disease and may benefit from prevention of and treatment for cardiovascular risk factors.
Early Prediction of Stable MR4.5 By Achievement of 2.8 Log Reduction in BCR-ABL1 qPCR Levels at 6 Months in Patients with Chronic Myeloid Leukemia Treated with Frontline Imatinib
Authors: Aisling Nee, Jeffrey H. Lipton, Dennis Dong Hwan Kim
Journal: Blood (2018)