tbuckley/cabot-search huggingface dataset:
Abstract 21033: Effect of Baseline Antiarrhythmic Drug on Outcomes With Ablation in Ischemic Ventricular Tachycardia: A Vanish Substudy
Authors: Ratika Parkash, Isabelle Nault, Lena Rivard, Lorne Gula, Vidal Essebag, Pablo Nery, Stanley Tung, Jean-Marc Raymond, Laurence Sterns, Steve Doucette, George Wells, Anthony Tang, William Stevenson, John Sapp
Journal: Circulation (2017)

Introduction: The VANISH trial enrolled patients with prior myocardial infarction, an implanted defibrillator and ventricular tachycardia (VT) despite antiarrhythmic (AAD) drugs and compared the effectiveness of escalated AAD therapy to catheter ablation. We sought to compare the effectiveness of these interventions in patients with sotalol-refractory VT versus amiodarone-refractory VT. Methods: All patients enrolled in the VANISH study were included (n=259). VT recurrence was compared in patients despite amiodarone (amio-refractory) as compared to non-amiodarone drugs (sotalol-refractory). Outcomes were a composite of death, VT storm, appropriate ICD shock, each of these components and any ventricular arrhythmia. Results: At baseline, 169 (65.2%) were amio-refractory and 90 (34.7%) were sotalol-refractory (1 patient was enrolled with VT despite procainamide). Amio-refractory patients had more renal insufficiency (23.7% vs 10%, p=0.0008), worse NYHA class (82.3% II/III vs 65.5%, p=0.0003), and lower ejection fraction (29 ± 9.7% vs 35.2 ± 11%, p&lt;0.0001). After adjusting for these baseline differences, there was no difference in mortality between the two groups. When examined within the escalated drug therapy arm, amio-refractory patients had a higher incidence of the composite outcome (HR 1.94, 95%CI (1.14, 3.29), p=0.0144), and a trend to higher mortality (HR 2.40, 95%CI (0.93, 6.22), p=0.07), while no difference in outcomes were observed within the ablation treatment group. Within the amio-refractory group, ablation resulted in significant reduction of any ventricular arrhythmia (HR 0.53, 95%CI (0.31, 0.9), p=0.020). Sotalol-refractory patients had trends towards higher mortality and VT storm with ablation, with no effect on ICD shocks. Conclusions: The benefit of catheter ablation is greater for patients with amio-refractory VT than for patients with sotalol-refractory VT who are then switched to amiodarone.
Anti-melanoma activity of the bisphosphonate ester APOMINE™ is independent of Ras farnesylation and apoptotic cell death in human melanoma cell lines
Authors: Alan Pourpak, Robert T. Dorr, Ross O. Meyers, Marianne B. Powell, Steven P. Stratton
Journal: Cancer Research (2005)

4305   APOMINE™ is a synthetic bisphosphonate ester and novel hypocholesterolemic agent that accelerates the degradation of HMG-CoA reductase and has potential osteoanabolic activity. It has also been shown to selectively inhibit cell proliferation and induce tumor cell apoptosis through the farnesoid X receptor. APOMINE™ has been shown to rapidly induce caspase-3 activation in HL-60 promyelocytic leukemia cells. APOMINE™ has also demonstrated activity against melanoma in a transgenic murine melanoma prevention model as well as a Phase I clinical trial. We hypothesized that this anti-melanoma activity is due to the inhibition of isoprenoid synthesis with a subsequent decrease in Ras prenylation and activation. The aims of this current study are: 1) To investigate the degree of cytotoxicity of APOMINE™ in human melanoma cell lines, 2) To determine the method of cell death and cell-cycle effects, and 3) To examine the modulation of Ras activity by APOMINE™. The 5 day IC 50  of APOMINE™ in the A375 human melanoma cell line was 21.3 μM. Following a 3 hr exposure at 50 μM, APOMINE™ inhibited DNA synthesis by 40% as measured by  3 H-thymidine incorporation. Similar experiments looking at RNA and protein synthesis showed insignificant effects. Flow cytometric analysis of Annexin V-FITC and propidium idodide staining indicated that cytotoxicity in melanoma cells is mediated through a predominantly non-apoptotic pathway. Western blot analysis confirmed the lack of caspase-3 activation by APOMINE™. Cell cycle analysis demonstrated a 15% increase in the G1 fraction following a 2-day exposure. To determine if APOMINE™ blocked melanoma carcinogenesis through a decrease in N-Ras activity, the A375 human melanoma cell line (which contains a constitutively active mutant B-Raf protein) was compared to the UACC 3093 human melanoma cell line (which contains a constitutively active mutant N-Ras protein). Cytotoxic potency of APOMINE™ was equivalent between the two cell lines. Western blot analysis demonstrated a decrease in total N-Ras protein levels but not a shift from farnesylated to unfarnesylated protein as seen with the farnesyl transferase inhibitor FTI-277. Downstream of Ras, APOMINE™ decreased total ERK protein levels along with phosphorylated levels in both the A375 and UACC 3093 cells, in contrast to the MEK inhibitor PD98059, which inhibited ERK phosphorylation but not expression. From these results, it appears that APOMINE™ cytotoxicity against human melanoma cells is mediated by an alternative, non-apoptotic mechanism. (This work was supported by PHS CA27502).
Abstract 18205: Successful Implementation of a Tele-visit Multidisciplinary Program
Authors: Ami Bhatt, Sarah Sossong, Ada Stefanescu, Lee H Schwamm
Journal: Circulation (2015)

Objectives: To design, implement and assess a patient and physician centered virtual visit program. Methods: Patients within the Cardiology and Neurology departments were enrolled in a real-time videoconferencing virtual visits program between April 1st 2014 and June 3rd 2015. Surveys were sent to patients who had at least one virtual visit between in the first 8 months to assess response to the use of the system and satisfaction, including the Consumer Assessment of Healthcare Providers and Systems survey (CAHPS). Results: There were 131 virtual visits in Cardiology and 419 visits in Neurology. The great majority of patients (83%) responded that they would definitely recommend a virtual visit to family or friends. Patients found the platform easy to use, with 74% of patients easily installing the product. Despite 42.5% reporting at least one technical problem, the overall patient satisfaction was high based on the CAHPS measures (Figure 1), and more than half of patients said they would even be willing to pay an up to $50 copay if needed for such visits. More than half of patients and providers felt that the quality of the visit was the same as in the office. While 45% of Cardiology patients felt the same during a virtual visit as in the office, 45% felt a stronger connection in person. Most providers felt virtual visits were either more efficient (38.5%) or just as long as office visits (50%), while 90% of patients thoughts their clinicians spent just as much time with them. Only 23.2% of patients overall however felt that a telephone call could definitely have addressed the same issue, emphasizing the value of the video conferencing platform. Conclusion: Virtual visits are well received by patients and providers, and considered by both to be efficient and useful. Implementing a virtual visit program with a design approach to assess and respond promptly to user feedback has encouraged adoption and holds promise for increasing the scale and integration into models of care delivery.
ASO Therapy: Hope for Genetic Neurological Diseases
Authors: Christopher C. Muth
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect of nonpermissive HLA-DPB1 mismatches after unrelated allogeneic transplantation with in vivo T-cell depletion
Authors: Betül Oran, Rima M. Saliba, Yudith Carmazzi, Marcos de Lima, Gabriela Rondon, Sairah Ahmed, Amin Alousi, Borje S. Andersson, Paolo Anderlini, Michelle Alvarez, Qasier Bashir, Stefan Ciurea, Marcelo Fernandez-Vina, Chitra Hosing, Partow Kebriaei, Martin Korbling, Pedro Cano, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Uday Popat, Katy Rezvani, Muzaffar Qazilbash, Elizabeth J. Shpall, Richard E. Champlin, Kai Cao
Journal: Blood (2018)
Modern diagnosis of GERD: the Lyon Consensus
Authors: C Prakash Gyawali, Peter J Kahrilas, Edoardo Savarino, Frank Zerbib, Francois Mion, André J P M Smout, Michael Vaezi, Daniel Sifrim, Mark R Fox, Marcelo F Vela, Radu Tutuian, Jan Tack, Albert J Bredenoord, John Pandolfino, Sabine Roman
Journal: Gut (2018)

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) &gt;6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET &lt;4% and &lt;40 reflux episodes on pH-impedance monitoring off proton pump inhibitors. Reflux-symptom association on ambulatory reflux monitoring provides supportive evidence for reflux triggered symptoms, and may predict a better treatment outcome when present. When endoscopy and pH or pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (histopathology scores, dilated intercellular spaces), motor evaluation (hypotensive lower oesophageal sphincter, hiatus hernia and oesophageal body hypomotility on high-resolution manometry) and novel impedance metrics (baseline impedance, postreflux swallow-induced peristaltic wave index) can add confidence for a GERD diagnosis; however, diagnosis cannot be based on these findings alone. An assessment of anatomy, motor function, reflux burden and symptomatic phenotype will therefore help direct management. Future GERD management strategies should focus on defining individual patient phenotypes based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the oesophagogastric junction and psychometrics defining symptomatic presentations.
Use of chemotherapy for patients with stage IV non-small cell lung cancer.
Authors: Sadaf Huma Waqar, Saiama Naheed Waqar, Siddhartha Devarakonda, Feng Gao, Cliff Grant Robinson, Varun Puri, Ramaswamy Govindan, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2015)

e19010 Background: Most of the information on the use of chemotherapy (CT) for patients with non-small cell lung cancer (NSCLC) has been obtained from SEER-Medicare, which includes only patients older than 65 years. The National Cancer Data Base (NCDB) collects data on patient demographics, treatment and outcomes for more than 70% of patients (pts) diagnosed in the US. We investigated the use of CT among patients with stage IV NSCLC on this large database. Methods: All pts diagnosed with stage IV NSCLC between the years 2000 and 2012 were identified through the NCDB public benchmark report. The frequency of CT use was evaluated according to year of diagnosis, age, gender, race, histology, hospital type, insurance and household income. Results: Among the 529,806 pts included in the study, 274,341 (51.7%) received CT. The use of CT was inversely related to age (73.8%, 63.7%, 51.8% and 28.6% for ages 20-39, 40-59, 60-79 and 80 or above respectively, P < 0.001). Other variables associated with increased use of CT were adenocarcinoma histology, non-black race, academic hospitals, higher household income and private insurance. There was an increase in the use of CT during the study period from 47.5% in 2000 to 53.5% in 2012 (P < 0.001). This increase was more pronounced in pts aged 60-79 (45.8% in 2000 to 55.1% in 2012) and 80 or older (20.5% to 29.3%) than in ages 40-59 (61.1% to 65.3%). Conclusions: Although there has been an increase in the use of CT in pts with stage IV NSCLC, there are still significant disparities according to demographics, hospital type and income. Since CT has been associated with improved survival in pts with metastatic lung cancer, reducing these disparities may eventually lead to an overall improvement in the outcomes for this population.
Abstract 17467: Percutaneous Coronary Intervention Among Patients With non-ST-segment Elevation Myocardial Infarction and Unstable Angina: Findings From the Improving Care for Cardiovascular Disease in China Project
Authors: Qing Yang, Ying Wang, Jing Liu, Jun Liu, Yongchen Hao, Yong Huo, Sidney Smith, Gregg Fonarow, Changsheng Ma, Junbo Ge, Kathryn Taubert, Louise Morgan, Yang Guo, Wei Wang, Yujie Zhou, Dong Zhao
Journal: Circulation (2016)

Introduction: The clinical guidelines recommended PCI for high risk patients of non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA), few studies have assessed PCI treat...
Sox11 gene disruption causes congenital anomalies of the kidney and urinary tract (CAKUT)
Authors: Yasmine Neirijnck, Antoine Reginensi, Kirsten Y. Renkema, Filippo Massa, Vladimir M. Kozlov, Haroun Dhib, Ernie M.H.F. Bongers, Wout F. Feitz, Albertien M. van Eerde, Veronique Lefebvre, Nine V.A.M. Knoers, Mansoureh Tabatabaei, Herbert Schulz, Helen McNeill, Franz Schaefer, Michael Wegner, Elisabeth Sock, Andreas Schedl
Journal: Kidney International (2018)
Impaired long-term immune protection following pneumococcal 13-valent/23-valent polysaccharide vaccine in systemic lupus erythematosus (SLE)
Authors: Karim Sacre, Tiphaine Goulenok, Mathilde Bahuaud, Chrystel Francois, Marie Claude Van der Haegen, Jean-François Alexandra, Pierre Aucouturier, Maria Hurtado-Nedelec, Helene Moins-Teisserenc, Frédéric Batteux, Thomas Papo
Journal: Annals of the Rheumatic Diseases (2018)

Although patients with systemic lupus erythematosus (SLE) are at increased risk for Streptococcus pneumoniae infection,1 2 vaccination coverage remains dramatically low in SLE,3 and efficacy of the now recommended prime-and-boost strategy using 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is not known.

Consecutive patients with SLE admitted in our daycare hospital unit were prospectively enrolled to receive PCV13 followed by PPSV23 8 weeks later. Immune protection, defined by an antigen-specific IgG concentration ≥1.3 µg/mL for at least 70% of seven pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F and 23F), was assessed at baseline, 2 and 12 months. Patients were defined as ‘long-term protected (LTP)’ when seroconversion was observed 2 months and 12 months after PCV13 shot. Patients were considered ‘short-term protected (STP)’ when seroconversion was observed 2 months but no more at 12 months after PCV13 shot. Patients were ‘not protected (NP)’ when seroconversion occurred neither 2 months nor 12 months after PCV13 shot. Laboratory tests included the analysis of blood …
Response to: ‘Statins in systemic lupus erythematosus’ by Abud-Mendoza
Authors: Hilda J I de Jong, Tjeerd P van Staa, Jan Willem Cohen Tervaert
Journal: Annals of the Rheumatic Diseases (2018)

It was with great interest that we read the correspondence of Abud-Mendoza1 on our recent paper in which we described a decreased risk of developing systemic lupus erythematosus (SLE) in statin users who continued their therapy for >1 year.2

We agree that prevention of cardiovascular disease in rheumatic diseases is of great importance.3 Whether statins decrease disease activity in SLE is, however, controversial since a recent meta-analysis of five controlled trials did not suggest any significant effect of statin therapy on Systemic Lupus Erythematosus Disease Activity Index.4

Unfortunately, in the UK’s Clinical Practice Research Datalink (CPRD)—an ongoing primary care database of anonymised medical records from general practitioners that was used in our study—no measurements for SLE activity before or after initiating statin therapy are available.2 We, however, do not think that statin …
GITR cosignal in ILC2s controls allergic lung inflammation
Authors: Hiroyuki Nagashima, Yuko Okuyama, Tsuyoshi Fujita, Takeo Takeda, Yasutaka Motomura, Kazuyo Moro, Takanori Hidaka, Koki Omori, Tsuyoshi Sakurai, Tomoaki Machiyama, Lishomwa C. Ndhlovu, Carlo Riccardi, Takanori So, Naoto Ishii
Journal: Journal of Allergy and Clinical Immunology (2018)
Graded Arrays of Spinal and Supraspinal V2a Interneuron Subtypes Underlie Forelimb and Hindlimb Motor Control
Authors: Marito Hayashi, Christopher A. Hinckley, Shawn P. Driscoll, Niall J. Moore, Ariel J. Levine, Kathryn L. Hilde, Kamal Sharma, Samuel L. Pfaff
Journal: Neuron (2018)

The spinal cord contains neural networks that enable regionally distinct motor outputs along the body axis. Nevertheless, it remains unclear how segment-specific motor computations are processed because the cardinal interneuron classes that control motor neurons appear uniform at each level of the spinal cord. V2a interneurons are essential to both forelimb and hindlimb movements, and here we identify two major types that emerge during development: type I neurons marked by high Chx10 form recurrent networks with neighboring spinal neurons and type II neurons that downregulate Chx10 and project to supraspinal structures. Types I and II V2a interneurons are arrayed in counter-gradients, and this network activates different patterns of motor output at cervical and lumbar levels. Single-cell RNA sequencing (RNA-seq) revealed type I and II V2a neurons are each comprised of multiple subtypes. Our findings uncover a molecular and anatomical organization of V2a interneurons reminiscent of the orderly way motor neurons are divided into columns and pools.
EGFR T790M and C797S Mutations as Mechanisms of Acquired Resistance to Dacomitinib
Authors: Yoshihisa Kobayashi, Toshio Fujino, Masaya Nishino, Takamasa Koga, Masato Chiba, Yuichi Sesumi, Shuta Ohara, Masaki Shimoji, Kenji Tomizawa, Toshiki Takemoto, Tetsuya Mitsudomi
Journal: Journal of Thoracic Oncology (2018)
MeCP2 as an Activator of Gene Expression
Authors: Patricia M. Horvath, Lisa M. Monteggia
Journal: Trends in Neurosciences (2018)

Rett syndrome is a neurodevelopmental disorder that primarily affects females and is caused by mutations in the methyl-CpG-binding-protein 2 (MECP2) gene. Initially, MeCP2 had been shown to be a repressor of gene transcription. In their 2008 paper, Chahrour and colleagues reported that MeCP2 could also function as a transcriptional activator. Rett syndrome is a neurodevelopmental disorder that primarily affects females and is caused by mutations in the methyl-CpG-binding-protein 2 (MECP2) gene. Initially, MeCP2 had been shown to be a repressor of gene transcription. In their 2008 paper, Chahrour and colleagues reported that MeCP2 could also function as a transcriptional activator.
Glioma through the looking GLASS: molecular evolution of diffuse gliomas and the Glioma Longitudinal Analysis Consortium
Authors: Kenneth Aldape, Samirkumar B Amin, David M Ashley, Jill S Barnholtz-Sloan, Amanda J Bates, Rameen Beroukhim, Christoph Bock, Daniel J Brat, Elizabeth B Claus, Joseph F Costello, John F de Groot, Gaetano Finocchiaro, Pim J French, Hui K Gan, Brent Griffith, Christel C Herold-Mende, Craig Horbinski, Antonio Iavarone, Steven N Kalkanis, Konstantina Karabatsou, Hoon Kim, Mathilde C M Kouwenhoven, Kerrie L McDonald, Hrvoje Miletic, Do-Hyun Nam, Ho Keung Ng, Simone P Niclou, Houtan Noushmehr, D Ryan Ormond, Laila M Poisson, Guido Reifenberger, Federico Roncaroli, Jason K Sa, Peter A E Sillevis Smitt, Marion Smits, Camila F Souza, Ghazaleh Tabatabai, Erwin G Van Meir, Roel G W Verhaak, Colin Watts, Pieter Wesseling, Adelheid Woehrer, W K Alfred Yung, Christine Jungk, Ann-Christin Hau, Eric van Dyck, Bart A Westerman, Julia Yin, Olajide Abiola, Nikolaj Zeps, Sean Grimmond, Michael Buckland, Mustafa Khasraw, Erik P Sulman, Andrea M Muscat, Lucy Stead
Journal: Neuro-Oncology (2018)

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal Analysis Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities and, ultimately, improved outcomes for a patient population in need.