tbuckley/cabot-search huggingface dataset:
451. Successful Gene Transfer in Passively Immunized Mice With Immunologically-Inert AAVrh.10 Vectors
Authors: Ruchita Selot, Balaji Balakrishnan, Sabna Cheemadan, Sudha Govindarajan, Rupali Gadkari, N. Srinivasan, Giridhara R. Jayandharan
Journal: Molecular Therapy (2015)

The development of an AAV vector that can bypass pre-existing immunity in humans is crucial for universal application of this vector system. Among the diverse AAV serotypes, AAVrh.10 has shown rapid and sustained transduction at both adult and neonatal stages. The low cross-reactivity of AAVrh.10 has also been reported to help vector re-administration. In the present study, we evaluated if disruptions of immunogenic epitopes predicted on AAVrh.10 could lead to evasion of pre-existing neutralizing antibodies and result in enhanced gene expression. The immunogenic T cell and B cell epitopes on AAVrh.10 capsid were predicted by ElliPro server (Immune Epitope DataBase). Site directed mutagenesis was performed on the epitopic regions predicted with highest probabality on AAVrh.10 capsid. The generation of the mutated immunologically inert (i2) AAVrh.10 vector was confirmed by DNA sequencing. Highly purified stocks of self complementary AAVrh.10 wild type (WT) and AAVrh.10 i2 vector was generated by polyethyleinimine based triple transfection protocols. The efficiency of AAVrh.10i2 vector transduction in immunized mice was tested in C57BL/6 mice that were pre-treated with pooled immunoglobulin (n=6, 2mg IVIG/animal). After 24 hours, both mock-control and treated animals were injected with WT-AAVrh.10 and AAVrh.10-i2 vectors expressing luciferase as the transgene. The luciferase activity was documented by serial bioluminescence imaging in small animal imaging system. A Taqman based quantitative PCR was used for estimation of viral genome copy number in the gDNA isolated from liver tissue of experimental mice. A month after gene transfer, AAVrh.10-i2 (6 out of 6 animals) mutant vectors had considerable transgene expression in the presence of IVIG while gene expression was completely neutralized in all the mice injected with WT-AAVrh.10 vectors. This partial rescue in luciferase expression in the presence of IVIG was ~27 to 64 fold in comparison to WT vector administered animals. To further evaluate their long-term transduction potential, C57BL/6 mice that did not receive IVIG were followed up further. Seventy-two days post vector administration, animals that received AAVrh.10-i2 vector showed a 6.6 fold increase in hepatic luciferase expression when compared to the WT-AAVrh.10 vectors. This was further corroborated by an increase in viral genome copies (2.07 vs. 0.64) in the liver tissue of AAV-rh.10 i2 vector administered mice. Further studies are needed to generate optimal AAVrh.10 vectors with complete immune evasion potential. The development of such AAV vectors with an immunologically-inert phenotype augurs well for their potential use in human gene therapy.
Correlation of response with survival endpoints in patients with newly diagnosed and recurrent glioblastoma (GBM) treated on prospective North Central Cancer Treatment Group (NCCTG) clinical trials
Authors: K. A. Jaeckle, W. Wu, M. Kosel, P. J. Flynn, J. C. Buckner
Journal: Journal of Clinical Oncology (2008)

2024 Background: The high response rates observed in recent trials of GBM patients (pts) treated with VEGF inhibitors, and the ongoing search for early endpoints which facilitate the efficient evaluation of new agents, have renewed the focus on tumor response as a potential surrogate for survival. Methods: In newly diagnosed (N=1,359) and recurrent (N=357) GBM pts treated prospectively on NCCTG phase II or III trials, we correlated best response (BR) category (responder or non-responder) with survival endpoints (PFS, TTP and OS). A responder was defined by standard NCCTG criteria as CR, PR or REGR (regression), and non-responder defined as STAB (stable) or PROG (progression) following treatment. Log-rank tests and Cox proportional hazard models were used to compare differences between survival and progression for each category. Landmark analyses at different cut-points were used for OS (newly diagnosed: 26 wks; recurrent: 9 and 13 wks) and TTP/PFS (newly diagnosed: 13 wks; recurrent: 6 and 9 wks). Results: For newly diagnosed GBM, best response was CR (n=9), PR (n=17) and REGR (n=150) (176 pts, 13%). For recurrent GBM, BR was CR (n=1) and REGR (n=26) (27 pts, 7.6%). For responders, median time to response for newly diagnosed and recurrent pts were 14 and 7 wks. For newly diagnosed pts, 988 pts were alive (176 responders, 812 non-responders) at wk 26. Median OS for responders and non-responders were 36 and 28 wks, respectively (p=0.01). At week 13, 1173 pts were alive without PROG (189 responders, 984 non-responders). Median TTP for responders and non-responders were 47 and 34 wks, respectively (p=0.0002). For recurrent pts, 251 were alive at wk 9 (227 non-responders, 24 responders), with median OS of 18 and 31 wks respectively (p=0.13); 195 pts were alive at wk 6 without PROG (171 non-responders, 24 responders), and median TTP were 7 and 21 wks (p=0.02). Results were not significantly altered after adjustment for age, gender and ECOG status. Conclusions: In newly diagnosed GBM, tumor response correlated significantly with TTP, but the predictive effect for OS was less robust, albeit reaching significance. For recurrent pts, response was an acceptable surrogate for TTP/PFS, but not OS. No significant financial relationships to disclose.
TCT-747 Utility of isoproterenol challenge in predicting symptomatic response to myectomy in hypertrophic cardiomyopathy with occult obstruction
Authors: Megha Prasad, Jeffrey B. Geske, Hartzell Schaff, Paul Sorajja, Steve Ommen, Bernard j Gersh, Rick A. Nishimura
Journal: Journal of the American College of Cardiology (2015)
Analysis of Class I and II Histone Deacetylase Fails To Identify a Human Leukemia Specific Expression Profile.
Authors: Guillermo Garcia-Manero, Andy S. Quesada, Shirisha Maddipoti, Shaoqing Kuang, Weigang Tong, William G. Wierda, Carlos M. Bueso-Ramos, Hui Yang
Journal: Blood (2007)
TCT-492 Clinical Outcomes of a Fractional Flow Reserve-Guided Revascularization Strategy in Patients With Diabetes Mellitus. Results from a Single Center Registry
Authors: Mark W Kennedy, Rik Hermanides, Veemal Hemradj, Petra C Koopmans, Jan-Henk E Dambrink, Marcel Gosselink, Arnoud van ′t Hof, Jan Paul Ottervanger, Vincent Roolvink, Wouter Remkes, Aize van der Sluis, Harry Suryapranata, Elvin Kedhi
Journal: Journal of the American College of Cardiology (2015)
Immunomodulatory Thalidomide Analogs Do Not Affect Osteoprogenitor Differentiation and Low Concentration of Bortezomib Promotes It, While Both Agents Suppress Osteoclast Differentiation.
Authors: Shoso Munemasa, Akira Sakai, Yoshiaki Kuroda, Yoshiko Okikawa, Yuta Katayama, Hideki Asaoku, Tadahiko Kubo, Shoji Shimose, Akiro Kimura
Journal: Blood (2007)
Risk Prediction With Electronic Health Records
Authors: Benjamin A. Goldstein, Ann Marie Navar, Michael J. Pencina
Journal: JAMA Cardiology (2016)

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 Cardiology 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 Cardiology journal
TCT-207 Comparative efficacy &amp; safety of Prasugrel, Ticagrelor, standard &amp; high dose Clopidogrel in patients undergoing percutaneous coronary intervention (PCI): A network meta-analysis
Authors: Sukhchain Singh, Mukesh Singh, Navsheen Grewal, Sandeep Khosla
Journal: Journal of the American College of Cardiology (2015)
Cancer-related direct-to-consumer advertising: awareness, perceived impact, and associated patient and provider behavior
Authors: G. A. Abel, N. D. Hevelone, H. J. Burstein, J. C. Weeks
Journal: Journal of Clinical Oncology (2008)

6631 Background: Although direct-to-consumer advertising (DTCA) is increasingly prevalent, little is known about cancer patients' awareness of and behavior resulting from this controversial medium of medical communication. Methods: We administered a 41-item mailed questionnaire to consecutive breast and hematologic malignancy patients undergoing active chemotherapy or hormonal treatment at our institution. We report on the first 263 patients contacted. Results: We received 200 completed questionnaires (response rate 76.0%): 75.2% of patients had breast cancer (55.0% hormonal therapy, 20.2% chemotherapy) and 24.8% had hematologic malignancy. The median age category was 51–60. Overall, 87.5% [95% CI: 87.2, 87.8] reported having seen at least one advertisement for a cancer-related medication, most frequently epoetin alfa (Procrit) 61.5%, pegfilgrastim (Neulasta) 58.0%, trastuzumab (Herceptin) 51.0%, anastrozole (Arimidex) 39.0%, and letrozole (Femara) 33.0%. Patients most frequently reported seeing advertising on television (76.6%), in magazines (69.1%), in pamphlets (34.9%), and on the Internet (19.4%). There was no association of DTCA awareness with clinical or sociodemographic factors. Of those respondents aware of DTCA, a majority reported (“agreed” or “somewhat agreed”) it provided information in language they could understand (88.2%), made them aware of treatments they did not know about (65.7%), and helped them to have better discussions with their oncology provider (57.2%). On the other hand, 11.5% reported that DTCA made them less confident in their providers' judgment. Finally, 16.2% reported talking to their provider about an advertised medication [95% CI: 15.7, 16.6], although less than one-fifth of those reported receiving a prescription for the medication [18.5%; 95% CI: 15.7, 21.3]. Conclusion: Cancer patients are highly aware of cancer-related DTCA and find it accessible and useful. In this cohort, DTCA prompted a modest amount of patient-provider discussion but infrequent change in prescription treatments. No significant financial relationships to disclose.
Scrapped generalist training programme was working well, review concludes
Authors: Matthew Limb
Journal: BMJ (2016)

The broad based training programme introduced in 2012 by the UK Academy of Medical Royal Colleges had shown promise in improving medical education before it was closed to recruitment last year, a review of the programme has concluded.

An independent evaluation found that the programme was meeting key targets, and one of the review’s researchers told BMJ Careers that the decision to halt recruitment was a “surprise.”1 2 Health Education England (HEE) announced that it would stop recruitment last November, saying that places were being scrapped to help fill more general practice posts instead.

Alison Bullock, a professor at Cardiff University’s school of postgraduate medical and dental education, led an HEE funded evaluation of the broad based training programme for the Academy of Medical Royal Colleges. She said that the training could prepare doctors for a changing NHS and suggested that HEE might come to rethink its decision or modify the scheme. “I think there is a need for it,” she told BMJ Careers . “I hope this …
TCT-283 Distal Vessel Quality (DVQ) score as a predictor of short- and mid-term coronary artery bypass graft dysfunction: Towards the optimization of the revascularization strategy
Authors: Hector Cubero Gallego, Ignacio J. Amat-Santos, Pablo E. Garcia-Granja, Benigno Ramos, Hipolito Gutierrez, Carlos Cortes, Itziar Gomez
Journal: Journal of the American College of Cardiology (2015)
TCT-597 Two-Year Ischemic and Bleeding Outcomes After Coronary Intervention of Calcified vs. Non-Calcified Lesions Treated With Drug-eluting Stents: The ADAPT-DES Study
Authors: Philippe Genereux, Guillaume Marquis Gravel, Bernhard Witzenbichler, Giora Weisz, Thomas Stuckey, Michael Rinaldi, Franz-Josef Neumann, D. Christopher Metzger, Timothy D. Henry, David Cox, Peter L. Duffy, Ernest L. Mazzaferri, Girish B. Ramteke, Claire Litherland, Ajay J. Kirtane, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2015)
Progress in Endocrine Neoplasia
Authors: Samuel A. Wells
Journal: Clinical Cancer Research (2016)

Most endocrine tumors are benign, and afflicted patients usually seek medical advice because of symptoms caused by too much, or too little, native hormone secretion or the impingement of their tumor on a vital structure. Malignant endocrine tumors represent a more serious problem, and patient cure often depends on early diagnosis and treatment. The recent development of novel molecular therapeutics holds great promise for the treatment of patients with locally advanced or metastatic endocrine cancer. In this CCR Focus, expert clinical investigators describe the molecular characteristics of various endocrine tumors and discuss the current status of diagnosis and treatment. Clin Cancer Res; 22(20); 4981-8. ©2016 AACR See all articles in this CCR Focus section, "Endocrine Cancers Revising Paradigms".
Up-Regulation of Genes Involved in Folate Metabolism Characterize Late but Not Early Relapse in Childhood Acute Lymphoblastic Leukemia.
Authors: Laura Hogan, Deepa Bhojwani, Jinhua Wang, Debra Morrison, Jun J Yang, Yutong Zhang, Jiri Zavadil, Gregory Condos, Stephen P Hunger, Cheryl L. Willman, Mary V. Relling, Elizabeth Raetz, William L. Carroll
Journal: Blood (2009)
HIV Testing and Outcomes Among Hispanics/Latinos — United States, Puerto Rico, and U.S. Virgin Islands, 2014
Authors: Shubha Rao, Puja Seth, Tanja Walker, Guoshen Wang, Mesfin S. Mulatu, John Gilford, Emilio J. German
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

The 2015 National HIV/AIDS Strategy provides an updated plan to address health disparities in communities at high risk for human immunodeficiency virus (HIV) infection (1,2). Hispanics/Latinos* are disproportionately affected by HIV in the United States. In 2014, 23% of HIV diagnoses were among Hispanics/Latinos, who represented 16% of the U.S. population (3). To examine HIV testing services, CDC analyzed 2014 data from the National HIV Prevention Program Monitoring and Evaluation (NHM&E) system submitted by 60 CDC-funded health departments† and 151 community-based organizations. Among Hispanics/Latinos tested, gay, bisexual, and other men who have sex with men (MSM) had the highest percentage of HIV diagnoses (2%). MSM accounted for 19.8% of HIV test events conducted among Hispanics/Latinos and 63.8% of Hispanics/Latinos who received an HIV diagnosis in non-health care settings.§ Approximately 60% of Hispanics/Latinos who received an HIV diagnosis were linked to HIV medical care within 90 days; this percentage was lower in the South than in other U.S. Census regions. HIV prevention programs that are focused on expanding routine HIV screening and targeting and improving linkage to medical care and other services (e.g., partner services) for Hispanics/Latinos can help identify undiagnosed HIV cases and reduce HIV transmission.
The Pro-Inflammatory Cytokine Interleukin-1 Is Essential for Clonal Expansion and Disease Progression in Acute Myeloid Leukemia
Authors: Alyssa Carey, Megan M Cleary, David K Edwards, Christopher A. Eide, Elie Traer, Shannon K. McWeeney, Jeffrey W. Tyner, Grover C. Bagby, Brian J. Druker, Anupriya Agarwal
Journal: Blood (2015)
GW27-e0774 Electrocardiogram Predictors of Transition from Idiopathic Outflow Tract Ventricular Premature to Monomorphic Tachycardia
Authors: Sun Yuanjun, Xianjie Xiao, Xiaomeng Yin, Dong Chang, Yingxue Dong, Lianjun Gao, Yanzong Yang, Yunlong Xia
Journal: Journal of the American College of Cardiology (2016)
Abstract MP026: Does the Replacement of Moderate-Intensity with Vigorous-Intensity Physical Activity Further Reduce All-Cause and Cardiovascular Mortality?
Authors: Eric J Shiroma, Howard D Sesso, I-Min Lee
Journal: Circulation (2012)

The 2008 US federal guidelines require a minimum of 150 minutes/week of moderate-intensity, or 75 minutes/week of vigorous-intensity physical activity, or an equivalent combination of the two, for health benefits. Thus, they assume a 2:1 equivalence between the two intensities of activity; i.e., 2 minutes of moderate-intensity activity is equivalent to 1 minute of vigorous-intensity activity. However, no studies have specifically examined whether this assumption is correct. Purpose: To examine the effect of replacing 150 minutes/week of moderate-intensity with 75 minutes/week of vigorous-intensity physical activity on all-cause and cardiovascular disease (CVD) mortality. Methods: 8,859 men (mean age, 66.4 yr) from the Harvard Alumni Health Study, free from CVD and cancer, were followed from 1988 to 2008. At baseline (1988) and in 1993, men reported physical activity (blocks walked, stairs climbed, and a listing of sports/recreational activities and participation time). Time spent per week in sports/recreational activities of moderate-intensity (3 to &lt;6 METs, or multiples of resting metabolic rate) was summed and expressed as units (or fraction of units) of 150 minutes/week. Similarly, time spent in vigorous-intensity (≥6 METs) sports/recreational activities was summed, expressed as units (or fraction of units) of 75 min/week. Total and cause-specific mortality was identified from the National Death Index. Cox proportional hazards models calculated the risks of all-cause and CVD mortality, examining the effect of replacing 150 minutes/week of moderate-intensity with 75 minutes/week of vigorous-intensity physical activity, controlling for the total amount of physical activity. Results: During follow-up, 4,064 men died, including 1,192 from CVD. In multivariate analyses, controlling for the total physical activity, age, smoking, intakes of alcohol, vegetable, fruit, and saturated fat, and total caloric intake, replacing 150 minutes/week of moderate-intensity with 75 minutes/week of vigorous-intensity physical activity was associated with an additional 2% reduction in all-cause mortality (Hazard Ratio (95% confidence interval) = 0.98 (0.96, 1.00); p = 0.05), and an additional 5% reduction in CVD mortality (0.95 (0.92, 0.99); p = 0.02). Conclusions: The assumption that 2 minutes of moderate-intensity activity is equivalent to 1 minute of vigorous-intensity activity under current federal guidelines is not strictly correct. Vigorous-intensity physical activity is associated with additional risk reduction for CVD mortality compared to moderate-intensity physical activity. Although there is an added, statistically significant benefit of vigorous-intensity over moderate-intensity physical activity, the magnitude of benefit is small.
Nystagmus and Lower Extremity Hyperalgesia After Colectomy
Authors: Alberto Vogrig, Tiziano Zanoni, Giuseppe Moretto
Journal: JAMA (2016)

A 47-year-old man with severe Crohn disease developed nystagmus and lower extremity hyperalgesia after elective colectomy and follow-up surgery for an enterocutaneous fistula. MRI of the brain showed hyperintensity in both medial thalami. What would you do next?
TCT-513 ABSORB III PK: Pharmacokinetics of Everolimus Eluted from the Absorb Bioresorbable Vascular Scaffold (BVS)
Authors: David Rizik, Louis A. Cannon, Stephen Ellis, Gregg W. Stone, Maureen Kennedy, Karine Piard-Ruster, Peter Staehr, Dean J. Kereiakes
Journal: Journal of the American College of Cardiology (2015)
Treatment of High Risk MDS and AML Post-MDS with Azacytidine (AZA): Preliminary Results of the French ATU Program.
Authors: Claire Fabre, Fatsiha Chermat, Laurence Legros, Sophie Park, François Dreyfus, Françoise Isnard, Florence Nowak, Anne Marfaing, Stéphane de Botton, Marie-Pierre Noel, Christophe Fruchart, Thomas Prebet, Norbert Vey, Caroline Dartigeas, Pierre Fenaux
Journal: Blood (2006)
Procalcitonin to guide taking blood cultures in the intensive care unit; a cluster-randomized controlled trial
Authors: P.J. van der Geest, M. Mohseni, D. Nieboer, S. Duran, A.B.J. Groeneveld
Journal: Clinical Microbiology and Infection (2016)

We aimed to study the safety and efficacy of procalcitonin in guiding blood cultures taking in critically ill patients with suspected infection.We performed a cluster-randomized, multi-centre, single-blinded, cross-over trial. Patients suspected of infection in whom taking blood for culture was indicated were included. The participating intensive care units were stratified and randomized by treatment regimen into a control group and a procalcitonin-guided group. All patients included in this trial followed the regimen that was allocated to the intensive care unit for that period. In both groups, blood was drawn at the same moment for a procalcitonin measurement and blood cultures. In the procalcitonin-guided group, blood cultures were sent to the department of medical microbiology when the procalcitonin was >0.25 ng/mL. The main outcome was safety, expressed as mortality at day 28 and day 90.The control group included 288 patients and the procalcitonin-guided group included 276 patients. The 28- and 90-day mortality rates in the procalcitonin-guided group were 29% (80/276) and 38% (105/276), respectively. The mortality rates in the control group were 32% (92/288) at day 28 and 40% (115/288) at day 90. The intention-to-treat analysis showed hazard ratios of 0.85 (95% CI 0.62-1.17) and 0.89 (95% CI 0.67-1.17) for 28-day and 90-day mortality, respectively. The results were deemed non-inferior because the upper limit of the 95% CI was below the margin of 1.20.Applying procalcitonin to guide blood cultures in critically ill patients with suspected infection seems to be safe, but the benefits may be limited.ClinicalTrials.gov identifier: ID NCT01847079. Registered on 24 April 2013, retrospectively registered.
ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions
Authors: Jonathan AC Sterne, Miguel A Hernán, Barnaby C Reeves, Jelena Savović, Nancy D Berkman, Meera Viswanathan, David Henry, Douglas G Altman, Mohammed T Ansari, Isabelle Boutron, James R Carpenter, An-Wen Chan, Rachel Churchill, Jonathan J Deeks, Asbjørn Hróbjartsson, Jamie Kirkham, Peter Jüni, Yoon K Loke, Theresa D Pigott, Craig R Ramsay, Deborah Regidor, Hannah R Rothstein, Lakhbir Sandhu, Pasqualina L Santaguida, Holger J Schünemann, Beverly Shea, Ian Shrier, Peter Tugwell, Lucy Turner, Jeffrey C Valentine, Hugh Waddington, Elizabeth Waters, George A Wells, Penny F Whiting, Julian PT Higgins
Journal: BMJ (2016)

Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I ("Risk Of Bias In Non-randomised Studies - of Interventions"), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.