tbuckley/cabot-search huggingface dataset:
Trabedersen (AP 12009) in the treatment of patients with advanced tumors: Completion of dose-escalation and first efficacy data.
Authors: H. Oettle, A. Hilbig, T. Seufferlein, T. Luger, R. M. Schmid, G. von Wichert, S. Schmaus, H. Heinrichs, K. Schlingensiepen
Journal: Journal of Clinical Oncology (2010)

2611 Background: Trabedersen (AP 12009) is a TGF-β2-specific antisense oligonucleotide. In a randomized and active-controlled phase IIb study in high-grade glioma patients, a clear survival benefit for trabedersen treatment over standard chemotherapy was found. In this study we evaluate the maximum tolerated dose (MTD), safety, pharmakokinetics, and efficacy of intravenous treatment with trabedersen in patients (pts) with other advanced solid tumors. Methods: In the open label, multicenter, dose-escalation phase I/II study, 33 pts with advanced pancreatic carcinoma (PancCa, stage IVA/IVB, N=23), malignant melanoma (stage III/IV, N=5), or colorectal carcinoma (stage III/IV, N=5) were enrolled in several cohorts. Pts were treated intravenously with trabedersen as 2nd to 4th-line therapy as monotherapy with escalating doses in 2 treatment schedules (1st schedule: 7d on, 7d off; 2nd schedule: 4d on, 10d off; up to 10 cycles). Results: Trabedersen showed high safety and tolerability. The only expected adverse reaction identified was nonserious, transient thrombocytopenia. Within the 1st schedule, MTD was established at 160 mg/m2/d. In the 2nd schedule dose escalation was stopped after the 4th cohort without reaching a MTD, as a well tolerated dose (140 mg/m2/d) with promising efficacy was identified. The median overall survival for pts with advanced PancCa treated with this dose (N=5) was 13.4 months. Further promising efficacy data include the following: a PancCa patient had a complete, sustained response of liver metastasis and is alive 49 months after enrollment; a melanoma patient survived 13.8 months, one melanoma patient is still alive after 12.8 months. Conclusions: Currently the study continues with the treatment of 24 pts with pancreatic carcinoma or malignant melanoma with a dose of 140 mg/m2/d. A randomized, active-controlled study is in preparation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antisense Pharma GmbH
Motion Compensated Ultrasound Imaging Allows Thermometry and Image Guided Drug Delivery Monitoring from Echogenic Liposomes
Authors: Kalyani Ektate, Ankur Kapoor, Danny Maples, Ahmet Tuysuzoglu, Joshua VanOsdol, Selvarani Ramasami, Ashish Ranjan
Journal: Theranostics (2016)

Ultrasound imaging is widely used both for cancer diagnosis and to assess therapeutic success, but due to its weak tissue contrast and the short half-life of commercially available contrast agents, it is currently not practical for assessing motion compensated contrast-enhanced tumor imaging, or for determining time-resolved absolute tumor temperature while simultaneously reporting on drug delivery.The objectives of this study were to: 1) develop echogenic heat sensitive liposomes (E-LTSL) and non-thermosensitive liposomes (E-NTSL) to enhance half-life of contrast agents, and 2) measure motion compensated temperature induced state changes in acoustic impedance and Laplace pressure of liposomes to monitor temperature and doxorubicin (Dox) delivery to tumors.LTSL and NTSL containing Dox were co-loaded with an US contrast agent (perfluoropentane, PFP) using a one-step sonoporation method to create E-LTSL and E-NTSL.To determine temperature induced intensity variation with respect to the state change of E-LTSL and E-NTSL in mouse colon tumors, cine acquisition of 20 frames/second for about 20 min (or until wash out) at temperatures of 42°C, 39.5°C, and 37°C was performed.A rigid rotation and translation was applied to each of the "key frames" to adjust for any gross motion that arose due to motion of the animal or the transducer.To evaluate the correlation between ultrasound (US) intensity variation and Dox release at various temperatures, treatment (5 mg Dox/kg) was administered via a tail vein once tumors reached a size of 300-400 mm 3 , and mean intensity within regions of interest (ROIs) defined for each sample was computed over the collected frames and normalized in the range of [0,1].When the motion compensation technique was applied, a > 2-fold drop in standard deviation in mean image intensity of tumor was observed, enabling a more robust estimation of temporal variations in tumor temperatures for 15-20 min.due to state change of E-LTSL and E-NTSL.Consequently, a marked increase in peak intensity at 42°C compared to 37°C that corresponded with enhanced Dox delivery from E-LTSL in tumors was obtained.Our results suggest that echogenic liposomes provide a predictable change in tumor vascular contrast with temperature, and this property could be applicable to nanomonitoring of drug delivery in real time.
Being open: our policy on source code
Authors: Rafal T. Marszalek, Louisa Flintoft
Journal: Genome biology (2016)

One of the open source code criteria, according to the Open Source Definition, is no discrimination against fields of endeavor. What this means in practice is that tools released under OSI-compliant licenses cannot use the “for non-commercial use only” disclaimers. A common worry [9] is that this affects whether the tool can be commercialized:

Do open source licenses stop me from commercializing my code?

No – no matter which open source license is used.

Do open source licenses mean that others can commercialize my code?

By definition, the open source code can be commercialized by anyone: the code’s author, their institution, an independent commercial entity, a private person. Literally anyone. This is independent of the exact OSI-compliant license used.

How do I choose a license?

The good folks of Github came to the rescue and created the ‘Choose an open source license’ service [10] for this. You can also browse for an appropriate license on the Open Source Initiative website [8]. Although some users believe that open source code should never be released under licenses that are “copyleft” [11] (these are the licenses which require that any derivative of the code is released under the same license), an equally good argument can be made [12] for GPL license-compatible licenses (which often are “copyleft”). While the use of permissive licenses that are not “copyleft” is more in the spirit of open science, Genome Biology currently accepts all OSI-compliant licenses.

How do I go about licensing my source code from the legal point of view?

Only the owner of the intellectual property rights to the source code can license it. While Genome Biology requires that the source code is released under an OSI-compliant license, it is the authors’ responsibility to ensure that they are within their rights to use such a license in the first place. Morin and colleagues provide a handy guide for the authors on what to do before you release your code under any license [13].
Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival
Authors: Elisa V. Bandera, Valerie S. Lee, Lorna Rodriguez-Rodriguez, C. Bethan Powell, Lawrence H. Kushi
Journal: Clinical Cancer Research (2016)

Among patients with ovarian cancer, African American (AA) women experience poorer survival compared with other race/ethnicity groups. This has been attributed to differences in access to health care.We evaluated racial/ethnic differences in chemotherapy dosing and survival in a cohort study among members of Kaiser Permanente Northern California, and thus with equivalent access to health care. Analyses included epithelial-invasive ovarian cancer cases (n = 793) receiving adjuvant first-line therapy of carboplatin and paclitaxel with curative intent, with median follow-up of 50 months. Relative dose intensity (RDI) was computed for carboplatin and paclitaxel separately as dose administered per week divided by expected dose per week, and average RDI (ARDI) was then calculated for the regimen. Proportional hazards regression was used to calculate HRs and 95% confidence intervals (CIs) after adjusting for relevant covariates.Compared with whites, AAs were more likely to have dose reduction (ARDI < 85%), treatment delay, and early discontinuation. Hispanics were also more likely to have dose reduction, but less likely to have early discontinuation or treatment delay. After controlling for prognostic factors including ARDI, AA women had the worst survival. Compared with whites, adjusted HRs (95% CI) for overall mortality were 1.56 (1.01-2.39) for AAs; 0.89 (0.61-1.31) for Asians; and 1.41 (0.98-2.04) for Hispanics. Findings for ovarian cancer-specific mortality were similar.Disparities in ovarian cancer treatment and survival in AA persisted among women with equal access to care. These findings warrant further evaluation of biological, personal, and social factors that may be responsible for these differences. Clin Cancer Res; 22(23); 5909-14. ©2016 AACR.
PrEP, Truvada, and Gilead
Authors: Andrew Jack
Journal: BMJ (2016)

Who sets the price of pre-exposure prophylaxis for HIV in the UK, asks Andrew Jack 

Truvada is a fixed dose combination of tenofovir and emtricitabine produced by the US drug company Gilead. It has been licensed for the treatment of HIV-1 infection in adults for more than a decade.

Recent studies have shown it also effective in “treatment as prevention” or pre-exposure prophylaxis (PrEP) among people at high risk. The US Food and Drug Administration approved Truvada for PrEP in 2012.1 The World Health Organization recommended it in 2014.2 It is already reimbursed in France and included in several national strategies.3

PROUD, a clinical trial conducted in England and published in 2015, showed that it reduced HIV infection by 86%, with modest side effects.4 No other antiretrovirals have been studied in such detail for their potential use in PrEP. …
P0506 : Impaired HCV-specific cytotoxic T cell reactivity due to 4-1BB signalling adapter (TRAF1) down-regulation during persistent HCV infection is restored by IL-7 plus 4-1BBL treatment
Authors: E. Moreno-Cubero, E. Sanz-de-Villalobos, J. Míquel, R. Borobia, S. García-Garzón, A. Lázaro, A. González-Pretorious, C. Perna, M. Torralba, T. Hocine, J.R. Larrubia
Journal: Journal of Hepatology (2015)
Second Interim Analysis of a Phase 3 Study of Idelalisib (ZYDELIG®) Plus Rituximab (R) for Relapsed Chronic Lymphocytic Leukemia (CLL): Efficacy Analysis in Patient Subpopulations with Del(17p) and Other Adverse Prognostic Factors
Authors: Jeff P. Sharman, Steven E. Coutre, Richard R. Furman, Bruce D. Cheson, John M. Pagel, Peter Hillmen, Jacqueline C. Barrientos, Andrew D. Zelenetz, Thomas J. Kipps, Ian W. Flinn, Paolo Ghia, Michael Hallek, Bertrand Coiffier, Susan O'Brien, Eugen Tausch, Karl-Anton Kreuzer, Wendy Jiang, Mirella Lazarov, Daniel Li, Thomas M. Jahn, Stephan Stilgenbauer
Journal: Blood (2014)
End of Life
Authors: Christian T. Sinclair
Journal: JAMA (2005)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Punctuated copy number evolution and clonal stasis in triple-negative breast cancer
Authors: Ruli Gao, Alexander Davis, Thomas O McDonald, Emi Sei, Xiuqing Shi, Yong Wang, Pei-Ching Tsai, Anna Casasent, Jill Waters, Hong Zhang, Funda Meric-Bernstam, Franziska Michor, Nicholas E Navin
Journal: Nature Genetics (2016)
Disgraced Canadian researcher faces criminal charges for fraud
Authors: Caroline White
Journal: BMJ (2016)

Ranjit Kumar Chandra, the disgraced Canadian researcher who lost his libel case last summer against the Canadian Broadcasting Corporation (CBC), which had accused him of research fraud and financial deception, is to face criminal charges for defrauding the publicly funded Ontario Health Insurance Plan.

Detective staff sergeant Dorian Dwyer confirmed that the Ontario Provincial Police Health Fraud Investigation Unit, on behalf of the Ontario Ministry of Health and Long-Term Care, has issued a warrant for Chandra’s arrest for the “unlawful billing” of the province’s health plan of sums in excess of $C5000 (£2900; €3400; $3800). The exact figures are not yet known because investigations into the extent of the false …
Programme d’épidémiologie de terrain en Espagne
Authors: J. F. Martinez Navarro, D Herrera, Candi Sanchez Barco
Journal: Eurosurveillance (2001)

En 1994, l’Instituto de Salud Carlos III (ISCIII), dependant du Ministere espagnol de la Sante et du Consommateur (MSC), a cree le Programme d’epidemiologie de terrain (Programa de Epidemiologia Aplicada de Campo, PEAC). Ce programme est dirige par le Centre national d’epidemiologie, en collaboration avec l’Ecole nationale de Sante. Il est finance par la Direction generale de la Sante et du Consommateur du MSC et par les Comites sanitaires (Consejerias de Sanidad) des regions autonomes.
Caring for the Poor
Authors: James T. Hamilton
Journal: JAMA (1988)

<h3>To the Editor.</h3> —In his article entitled "Unconscious on a Corner...," Dr Hilfiker<sup>1</sup>clearly lays out the problem: good medical care for the indigent, but inadequate societal support during rehabilitation and recovery—inadequate shelter, food, and supervision to get the patient to follow-up appointments and see that he takes his medicine. The author also gives evidence of good medical care for the vast majority of our citizens. After defining the problem as inadequate social support for a small segment of our society, he states that<i>medicine</i>has "abandoned the poor" and that the answer is national health insurance! Do your editors not check for logical consistency in articles submitted, or do you really believe that medical care can ever make up for the social inadequacies listed in my first paragraph? If you do, please present some evidence for such a novel idea. Dr Hilfiker's article presents much evidence that it
Association Between Downregulation of POT1 Expression and Chromosome 7 Deletion, Response to Hypomethylation Agent Treatment, and Patient Survival in Myelodysplastic Syndromes
Authors: Yue Wei, Amit Verma, Monica Cabrero, Yu Jia, Hong Zheng, Zhihong Fang, Yiting Yu, Simona Colla, Zach Bohannan, Teresa V. Bowman, Jacqueline Boultwood, Guillermo Garcia-Manero
Journal: Blood (2014)
Cell Non-Autonomous Modulation Of Tumor Cell Responses To Pharmacological Inhibition Of The Proteasome
Authors: Eugen Dhimolea, Richard W.J. Groen, Catriona A. Hayes, Jana Jakubikova, Bariteau Megan, Jake E. Delmore, Hannah M. Jacobs, Julio-Cesar Marin, Gregory Della Penna, Douglas W. McMillin, Ana Acuna, Panisinee Lawasut, Nancy Kohl, Constantine S. Mitsiades
Journal: Blood (2013)
Strategies and benefits to effectively engage minority patients in their cancer care.
Authors: D. M. O'Brien, D. D. Hood, N. C. Katurakes, J. K. Harness, M. A. Bright, K. Chu
Journal: Journal of Clinical Oncology (2010)

e19501 Background: The National Cancer Institute Community Cancer Centers Program (NCCCP), a public-private research partnership with 16 community hospital cancer centers in 14 states, directs 40% of its NCI funding on efforts to reduce healthcare disparities. These cancer centers work with private practice physicians to provide care to cancer patients. The NCCCP seeks to reduce barriers for minority populations to: improve access to cancer care, increase understanding about this care, expand accrual to clinical trials, and offer support for navigating the health care system. These efforts support many of the priorities noted in the June 2009 ASCO Policy Statement: Disparities in Cancer Care and offer approaches that can be adopted by other cancer care providers. Methods: The strategies which will be presented have been developed and tested at many NCCCP sites and include programs to improve: race and ethnicity tracking, cultural awareness education, accrual to clinical trials, and targeted minority outreach efforts. Tools and resources which support these efforts will be discussed and are available on the NCI web site (http://ncccp.cancer.gov/About/Progress.htm). Results: The NCCCP sites will show that they have been able to develop outreach and screening to target specific minority groups, increase the number of patients screened for clinical trials, increase staff training on cultural awareness, and increase race and ethnicity tracking. The benefits to providers in adopting these strategies will be discussed and include: improved participation in clinical trials programs, being able to engage patients more effectively for improved compliance with their treatment, and increased patient satisfaction. Conclusions: These strategies and programs are being used in many different community settings to improve access to care and improved quality of care for minority cancer patients and can be easily adapted to other locations. Providers who are interested in working to reduce disparities in cancer care will find the experience of the NCCCP to be helpful. NCI intends to expand the NCCCP program in the spring of 2010 thus further employing these strategies to more communities to reduce cancer healthcare disparities. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genomic Health SenoRx Genomic Health
A validated high-pressure liquid chromatography analysis for determination of A77 1726, the active metabolite of leflunomide, in human plasma
Authors: Mjp Van Wanrooy, van Eric Roon, J Yska, Ttha Jansen, Pieternella Houtman, Gaw Bruyn, EN Griep, Jpl Spoorenberg, Jacobus Brouwers
Journal: Annals of the Rheumatic Diseases (2003)
Decitabine Can Increase the Induction of Regulatory γδ T Cells with Enhanced Immunosuppression on Graft-Versus-Host Disease From Adult Human Peripheral Blood Mononuclear Cells
Authors: Yongxian Hu, Yanjun Gu, Lixia Sheng, Huarui Fu, Kangni Wu, Lifei Zhang, Lizhen Liu, Shan Fu, Yulin Xu, Haowen Xiao, Xiaohong Yu, He Huang
Journal: Blood (2011)
The BH3 Mimetic, Small Molecule, ABT-737, Was Effective As Lympholytic Therapy in the MRL/lpr−/− Mouse Model of Autoimmune Lymphoproliferative Syndrome (ALPS)
Authors: Kennichi C. Dowdell, Lu Lianghao, V. Koneti Rao, Thomas A. Fleisher, Joao Bosco Oliveira
Journal: Blood (2011)
Oxaliplatin plus 5-fluorouracil/folinic acid as palliative treatment for progressive malignant gastrointestinal neuroendocrine carcinomas
Authors: U. Pape, N. Tiling, C. Bartel, U. Plöckinger, B. Wiedenmann
Journal: Journal of Clinical Oncology (2006)

14074 Background: Oxaliplatin in combination with 5-fluorouracil and folinic acid is an antitumoral agent with relatively low toxicity and satisfactory efficacy in several gastrointestinal neoplasms. However, it has not been studied in malignant gastrointestinal neuroendocrine carcinomas (NEC) for which platinum-based chemotherapy is a standard treatment with considerable toxicity. Methods: 16 patients (6 female, 10 male; mean age 57) with documented progress of histologically proven, irresectable, malignant NEC were retrospectively analyzed for safety and efficacy of cytotoxic treatment (from october 2001 to december 2005) according to the FOLFOX-4 regimen. Primary tumors were in the foregut in 9 (2 bronchial, 5 pancreas, 2 stomach), in the midgut in 3 (1 ileum, 2 coecum), and in the hindgut in 2 (1 colon, 1 rectum) patients. The primary tumor was unknown in 2 patients. No patient had clinical signs of hormone hypersecretion. NEC were low-grade malignant in 8 and high grade malignant in the remaining 8 cases. The ki67-index was ≥ 10% in 13 cases (81.3%). Results: A mean of 7.25 cycles (range 1–19) of FOLFOX-4 were administered. Stable disease for a minimum of 9 weeks was observed in 62.5% (10/16) for a mean duration of 19.4 weeks; overall mean time to progression (TTP) as measured by imaging studies was 17.8 weeks (range 2–70 weeks). Reasons for discontinuation of treatment included documented tumor progression in 8 cases (50%) and adverse events in 4 cases (25%) (grade II neurotoxicitiy in 3 cases and grade III neutropenia in 2 cases). 2 patients died during treatment due to tumor progression. 4 patients currently still receive FOLFOX-4 after a mean treatment period of 16 weeks. Side effects according to CTC-NCI-criteria include mild anemia (grade I: n=15), thrombocytopenia (I: n=4, II: n=1), neutropenia (I: n=1, III: n=2), increased serum creatinine (I: n=2), nausea (I: n=4, II: n=4, III: n=1), vomiting (I: n=2, II: n=2), and neurotoxicity (I: n=1, II: n=4). Conclusions: The FOLFOX-4 regimen was well tolerated and effective in progressive malignant NEC with increased proliferative potential. Response may be comparable to current standard regimens. FOLFOX-4 should be evaluated in a prospective controlled clinical trial. No significant financial relationships to disclose.
Mortality and Length of Stay in Teaching vs Nonteaching Hospitals
Authors: Mary Anne Schultz
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The comparative study of patient outcomes by Dr Rosenthal and colleagues<sup>1</sup>reestablishes why cost structures and pricing mechanisms in teaching hospitals may be justifiable and signals institutional providers everywhere that a nonprice basis for competition has already emerged.<sup>2</sup>That is, the price of managed care contracts matters, but so does the documented quality of care—something consumers and their employers have sought for a long time. It is well past the time for individual physicians, physician group practices, and advanced practice nurses to track patient outcomes for the purposes of quality improvement and for competitive positioning of their practices on a nonprice (quality-of-care) basis.<sup>2</sup>Consumers and their representatives, especially large employers, have demanded this information for years. The fact that better data on which to base managed care negotiations are lacking is unfortunate and, I hope, time limited. As Dr Iezzoni cautions,<sup>3</sup>"Mortality rates are, at best, a blunt instrument for comparing hospital quality."
Integrating Inflammasome Signaling in Sexually Transmitted Infections
Authors: Christopher Lupfer, Paras K. Anand
Journal: Trends in Immunology (2016)

Inflammasomes are cytosolic multiprotein platforms with pivotal roles in infectious diseases. Activation of inflammasomes results in proinflammatory cytokine signaling and pyroptosis. Sexually transmitted infections (STIs) are a major health problem worldwide, yet few studies have probed the impact of inflammasome signaling during these infections. Due to the dearth of appropriate infection models, our current understanding of inflammasomes in STIs is mostly drawn from results obtained in vitro, from distant infection sites, or from related microbial strains that are not sexually transmitted. Understanding how inflammasomes influence the outcome of STIs may lead to the development of novel and effective strategies to control disease and prevent transmission. Here we discuss and highlight the recent progress in this field.