tbuckley/cabot-search huggingface dataset:
Precision Treatment and Precision Prevention
Authors: Matthew W. Gillman, Ross A. Hammond
Journal: JAMA Pediatrics (2015)

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 Pediatrics 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 Pediatrics journal
Statistical controversies in clinical research: long-term follow-up of clinical trials in cancer
Authors: J. Cuzick
Journal: Annals of Oncology (2015)

Long-term follow-up is an important unmet need for the full analysis of new treatments for cancer. Earlier detection of cancer and more effective treatment have led to many more patients surviving for more than 5 and even 10 years, so that evaluating late recurrences and side-effects is an increasingly important issue. This is particularly relevant for oestrogen receptor-positive breast cancer, where the existence of late recurrences is well documented. However, survival for other cancers, notably prostate, colorectal and cervix cancer, has dramatically increased in recent years due to screening and better treatment of early lesions. Trials of preventive therapies have an even greater need for long follow-up. Here, we review these issues and suggest ways in which provision for long-term follow-up can be improved.
Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients
Authors: Stephan Ehrmann, Ferran Roche-Campo, Laetitia Bodet-Contentin, Keyvan Razazi, Jonathan Dugernier, Josep Trenado-Alvarez, Alexis Donzeau, François Vermeulen, David Thévoz, Metaxia Papanikolaou, Antoine Edelson, Héctor León Yoshido, Lise Piquilloud, Karim Lakhal, Carlos Lopes, Carlos Vicent, Arnaud Desachy, Gabriela Apiou-Sbirlea, Daniel Isabey, Laurent Brochard
Journal: Intensive Care Medicine (2015)
Expansion Cohorts in First-in-Human Solid Tumor Oncology Trials
Authors: Marc R. Theoret, Lee H. Pai-Scherf, Meredith K. Chuk, Tatiana M. Prowell, Sanjeeve Balasubramaniam, Tamy Kim, Geoffrey Kim, Paul G. Kluetz, Patricia Keegan, Richard Pazdur
Journal: Clinical Cancer Research (2015)

In 1962, the passage of the Kefauver-Harris Amendment to the 1938 Food, Drug, and Cosmetic Act required that sponsors seeking approval of new drugs demonstrate the drug's efficacy, in addition to its safety, through a formal process that includes "adequate and well-controlled" clinical trials as the basis to support claims of effectiveness. As a result of this amendment, FDA formalized in regulation the definitions of various phases of clinical investigations (i.e., phase I, phase II, and phase III). The clinical drug development paradigm for anticancer drugs intended to support marketing approval has historically followed this "phased" approach with sequential, stand-alone trials, with an increasing number of patients exposed to an investigational drug with each trial in order to fulfill the objectives of that particular stage in development. Increasingly, it is the Office of Hematology and Oncology Products' experience that commercial sponsors of solid tumor oncology drug development programs are amending ongoing phase I trials to add expansion cohorts designed to evaluate study objectives typical of later-phase trials. For investigational anticancer drugs that demonstrate preliminary clinical evidence of substantial antitumor activity early in clinical testing, use of expansion cohorts as a component of the solid tumor oncology drug development pathway, with appropriate measures to mitigate the risks of this approach, may fit in well with the goals and concepts described by FDA's expedited programs for serious conditions.
Whistling in the Dark
Authors: Daniel A. Solomon, Christopher H. Fanta, Bruce D. Levy, Joseph Loscalzo
Journal: New England Journal of Medicine (2012)

Shortness of breath, fever, and cough productive of yellow sputum developed in a 38-year-old woman soon after the birth of her third child. Although her symptoms initially resolved with antibiotics, an intermittent nonproductive cough, wheezing, and shortness of breath soon followed.
Obinutuzumab (GA101) is highly effective against chronic lymphocytic leukemia cells in ex vivo B-cell depletion irrespective of high-risk prognostic markers
Authors: L Ysebaert, E Laprévotte, C Klein, A Quillet-Mary
Journal: Blood Cancer Journal (2015)

The anti-CD20 monoclonal antibody rituximab has revolutionized the management of B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL). Addition of rituximab to the frontline standard chemotherapy (fludarabine–cyclophosphamide, FC) within the rituximab fludarabine cyclophosphamide regimen has recently shown to statistically increase both progression-free survival (PFS) and overall survival (OS) in the randomized CLL8 phase III trial of the German CLL Group.1 This was the first example of improved OS in first-line CLL, although restricted to those patients fit enough to receive FC chemotherapy. However, the translation of these results into the clinical setting is hampered by the fact that ca. one half of CLL patients are 72 years at the time of first therapy, 40% being aged more than 75 years2 with increased burden of comorbidities (for example, kidney function impairment) and thus not eligible for FC chemotherapy.
Mapping lung tumor promotion genes using AXB, BXA recombinant inbred (RI) strains
Authors: Lori Dwyer-Nield, Richard Radcliffe, Elizabeth Redente, Alvin Malkinson
Journal: Cancer Research (2008)

2242  Genes determine individual susceptibility to spontaneous and carcinogen-induced lung cancer in inbred mice. However, little is known about the genetic contribution to the promotion phase of lung tumorigenesis. Chronic treatment with the mouse lung tumor promoter, butylated hydroxytoluene (BHT), increases tumor number in certain inbred strains. Chronic BHT administration induces a chronic inflammatory response in strains susceptible to lung tumor promotion that consists of increased macrophage infiltration, vascular leakage, and elevated COX-1 and COX-2 expression. Herein we examine a panel of AXB, BXA recombinant inbred (RI, derived from sensitive A/J and resistant C57BL/6 mice) strains for sensitivity to 3-methylcholanthrene (MCA)-induced carcinogenesis, BHT-mediated tumor promotion, and lung damage, and to the inflammatory responses described above to examine their inter-relationships and map genetic loci responsible for each phenotype. Tumor promotion associates significantly with increased BAL macrophage infiltration, suggesting that these macrophages aid in the clonal expansion of MCA-initiated epithelial cells. A striking gender dependence was found in the ability of BHT to promote lung tumorigenesis; only males were promoted in one strain, only females in three others, with no gender dependence in the remaining strains. Tumor growth rate and multiplicity are genetically independent, since in two strains, both tumor growth rate and tumor multiplicity were increased by BHT, while only multiplicity was raised by BHT in other responsive strains. Another significant correlation occurs between BHT-induced increases in COX-1 and COX-2 expression. Of eight suggestive quantitative trait loci (QTLs) thus far detected, 4 map to sites previously described for susceptibility to lung inflammation and tumor promotion using the CXB RI strains (derived from BALB/cByJ and C57BL6), while 4 additional sites are novel. Mapping studies of additional AXB, BXA RI strains will verify and more finely resolve these QTLs and thus identify candidate genes. (Supported by CA33497).
Immune Receptors: Targets for Therapy of Leukemia/Lymphoma, Autoimmune Diseases and for the Prevention of Allograft Rejection
Authors: T A Waldmann
Journal: Annual Review of Immunology (1992)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
The Notch Mediator RBP-J in CD4 T Cells Plays a Crucial Role in the Induction of Allergic Asthma in Mice
Authors: Alex KleinJan, Marjolein de Bruijn, Menno van Nimwegen, Ingrid Bergen, Henk C. Hoogsteden, Derk Amsen, Rudi W. Hendriks
Journal: Journal of Allergy and Clinical Immunology (2013)
Streptomycin and Tuberculous Meningitis
Authors: R. Debre, None Thieffry, Ed. Brissaud, H. Noufflard
Journal: BMJ (1947)

Nineteen patients identified by <sup>125</sup>I, <sup>131</sup>I, or <sup>99m</sup>Tc-pertechnetate imaging as harboring a solitary “cold nodule” of the thyroid gland were evaluated further by <sup>67</sup>Ga-citrate thyroid scans. Histologic examination of the thyroid tumors was performed in all cases. Of the seven thyroid tumors shown to be malignant, only three selectively concentrated <sup>67</sup>Ga-citrate. Two of these were anaplastic carcinoma; the third was a mixed papillary-follicular carcinoma containing multiple foci of poorly differentiated cells. None of the 12 benign nodules in this investigation concentrated <sup>67</sup>Ga-citrate. These included follicular adenomas and colloid nodules. No cases of subacute or chronic lymphocytic thyroiditis were encountered. Our results indicate that although <sup>67</sup>Ga-citrate may be of value in identifying anaplastic thyroid tumors, it has limited application in the diagnosis of solitary cold nodules.
The American Society of Clinical Oncology's Efforts to Support Global Cancer Medicine
Authors: Gabriel N. Hortobagyi, Nagi S. El-Saghir, Tanja Cufer, Eduardo Cazap, Roselle de Guzman, Nicholas Anthony Othieno-Abinya, Jose Angel Sanchez, Doug Pyle
Journal: Journal of Clinical Oncology (2015)

Despite much progress in the management of malignant diseases, the number of new cases and cancer-related deaths continues to rise around the world. More than half of new cases occur in economically developing countries, where more than two thirds of cancer deaths are expected. However, implementation of all necessary steps to accomplish the dissemination of state-of-the-art prevention, diagnosis, and management will require increased allocation of resources, and, more importantly, harmonization of the efforts of hundreds of national and international public health agencies, policy-setting bodies, governments, pharmaceutical companies, and philanthropic organizations. More than 30% of the members of the American Society of Clinical Oncology (ASCO) reside and practice outside US borders, and more than half of attendees at all of the scientific congresses and symposia organized by ASCO are international. As cancer has become an increasingly global disease, ASCO has evolved as a global organization. The ASCO Board of Directors currently includes members from France, Brazil, and Canada. In 2013, the ASCO Board of Directors identified a number of strategic priorities for the future. Recognizing the importance of non-US members to the society, their first strategic priority was improving the society's service to non-US members and defining these members' identity in the international oncology community. This article reviews current ASCO activities in the international arena and its future plans in global oncology.
Pharmacologic and Therapeutic Applications of alpha2-Adrenoceptor Subtypes
Authors: R R Ruffolo, A J Nichols, J M Stadel, J P Hieble
Journal: The Annual Review of Pharmacology and Toxicology (1993)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
An Integrated view of the Molecular Toxinology of Sodium Channel Gating in Excitable Cells
Authors: G Strichartz, T Rando, G K Wang
Journal: Annual Review of Neuroscience (1987)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Cancer Immunotherapy Researchers Focus on Refining Checkpoint Blockade Therapies
Authors: Julie A. Jacob
Journal: JAMA (2015)

The origins of cancer immunotherapy date back more than 2 decades to when researchers explored ways to amplify the immune system to attack tumor cells. At the time, scientists hypothesized that tumors were able to evade immune survei l lance because tumor cells lacked costimulatory molecules required to signal T cells to the presence of the tumor. However, in the mid-1990s, James P. Allison, PhD, and his colleagues at the University of California, Berkeley, Cancer Research Laboratory discovered that rather than lack costimulatory molecules, tumor cel ls and other immune cel ls expressed inhibitory molecules that disabled T cells from recognizing and eliminating tumors. These early experiments compared tumor growth in mice that had received injections of cytotoxic T lymphocyte– associated molecule 4 (CTLA-4) antibodies with tumor growth in mice in a control group (Leach DR et al. Science. 1996;271: 1734-1736). Allison and his colleagues hypothesized that the antibodies would turn off CTLA-4, a receptor that dampens T-cell activity, and thus unleash an attack on the tumors. The experiment results were striking. “The idea was that the brakes come on at a certain point. If we just disabled the brakes, [the immune system] can keep going until it has time to kill the tumor mass. In the first experiment, in the control group, all the mice had to be euthanized because they grew big tumors. In the [treated] mice, the tumors had gone away,” recalled Allison, who at the time was director of the Cancer Research Laboratory. But when the data were published in Science in 1996, the response from the research community was more like a collective shrug than a buzz of excitement, recalled Allison, now the executive director of the Immunology Platform and chair of the department of immunology at the MD Anderson Cancer Center in Houston. “Cancer immunotherapy had a checkeredhistory,”he said, noting thatdisillusionment had set in among researchers after interleukin-2 and cancer vaccines failed to meet high expectations for their success. Despite the initial muted response to his work, and nearly 2 decades after the publication in Science, Allison received both the 2015 Lasker-DeBakey Clinical Medical Research Award and the 2015 American Society of Clinical Oncology’s Science of Oncology Award for his work that contributed to the development of cancer immunotherapy. Now, dozens of clinical trials are under way to study how these drugs work on several different types of cancers, and oncology researchers are trying to determine why these drugs are lifesavers for some patients but fail to help others.
Current Approaches in the Treatment of Parkinson's Disease
Authors: M Stacy, J Jankovic
Journal: Annual Review of Medicine (1993)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Detection of tumor cells in purged bone marrow and peripheral-blood mononuclear cells by polymerase chain reaction amplification of bcl-2 translocations.
Authors: R S Negrin, J Pesando
Journal: Journal of Clinical Oncology (1994)

PURPOSE To compare bone marrow (BM) before and after purging with monoclonal antibodies (MAbs) and complement with peripheral-blood mononuclear cells (PBMNCs) for tumor-cell contamination by amplification of t(14;18) sequences using the polymerase chain reaction (PCR). PATIENTS AND METHODS Sixty patients with non-Hodgkin's lymphoma (NHL) undergoing autologous BM transplantation were evaluated. Six BM biopsies were performed at the time of harvesting and evaluated morphologically for tumor involvement. The harvested BM was treated with a panel of anti-B-cell MAbs directed against CD9, CD10, CD19, and CD20, followed by rabbit complement. Clonogenic assays were performed before and after purging. DNA was extracted and t(14;18) sequences amplified by PCR. PBMNCs collected by apheresis for back-up purposes were similarly evaluated. RESULTS Fifteen patients (25%) were PCR-positive before BM purging. Following MAb- and complement-mediated purging, there was a reduction in the PCR-amplified signal in 10 patients (67%). There was no reduction in colony-forming unit granulocyte-macrophage (CFU-GM) colony growth following purging. Eight of these 15 patients (53%) had morphologic evidence of BM involvement at the time of harvesting. In these eight patients, only three had a reduction in the PCR-amplified products, as compared with all seven who were morphologically negative at the time of BM harvesting (P = .026). Fourteen of these 15 patients had PBMNCs collected near the time of BM harvesting and 12 (86%) were PCR-positive. CONCLUSION BM purging with MAbs and complement results in reduction in the number of t(14;18)-positive tumor cells, especially in those patients who have no morphologic evidence of BM disease at the time of harvesting. Purged BM was less contaminated with t(14;18)-positive cells than unpurged PBMNCs, which were frequently contaminated with tumor cells.
Doctors underwent "extreme sleep deprivation" in studies of effect on patient deaths
Authors: J. Lenzer
Journal: BMJ (2015)

<h3>Abstract</h3> We present three deep learning sequence prediction models for hemolysis, solubility, and resistance to non-specific interactions of peptides that achieve comparable results to the state-of-the art models. These predictive models share a common architecture of bidirectional recurrent neural networks (LSTM). These models are implemented in JavaScript so that they can be run on a static website without use of a dedicated server. This removes the cost, and long-term management of a server, while still enabling open and free access to the models. This “serverless” prediction model is a demonstration of edge computing bioinformatics and removes the dependence on cloud providers or self-hosting of resource-rich academic institutions. This is feasible because of the continued track of Moore’s law and ubiquitous hardware acceleration of deep learning computations on new phones and desktops.
Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity?
Authors: Chandra Mohan, Shervin Assassi
Journal: BMJ (2015)

Serological and proteomic biomarkers can help clinicians diagnose rheumatic diseases earlier and assess disease activity more accurately. These markers have been incorporated into the recently revised classification criteria of several diseases to enable early diagnosis and timely initiation of treatment. Furthermore, they also facilitate more accurate subclassification and more focused monitoring for the detection of certain disease manifestations, such as lung and renal involvement. These biomarkers can also make the assessment of disease activity and treatment response more reliable. Simultaneously, several new serological and proteomic biomarkers have become available in the routine clinical setting—for example, a protein biomarker panel for rheumatoid arthritis and a myositis antibody panel for dermatomyositis and polymyositis. This review will focus on commercially available antibody and proteomic biomarkers in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), dermatomyositis and polymyositis, and axial spondyloarthritis (including ankylosing spondylitis). It will discuss how these markers can facilitate early diagnosis as well as more accurate subclassification and assessment of disease activity in the clinical setting. The ultimate goal of current and future biomarkers in rheumatic diseases is to enable early detection of these diseases and their clinical manifestations, and to provide effective monitoring and treatment regimens that are tailored to each patient's needs and prognosis.
Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution.
Authors: L Fouillard, J P Laporte, M Labopin, S Lesage, F Isnard, L Douay, M Lopez, M Aoudjhane, P Zunic, N Cheron, J Stachowiak, M P Lemonnier, G Andreu, Y Belkacemi, M P Noël-Walter, P Morel, P Fenaux, J P Jouet, F Bauters, A Najman, N C Gorin
Journal: Journal of Clinical Oncology (1998)

To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution.A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement.Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS.This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.
Endoscopic ultrasound-guided biliary drainage with a novel fine-gauge balloon catheter: simplified technique using a coaxial guidewire
Authors: Takeshi Ogura, Wataru Takagi, Saori Onda, Daisuke Masuda, Toshihisa Takeuchi, Shinya Fukunishi, Kazuhide Higuchi
Journal: Endoscopy (2015)

For performance of endoscopic ultrasound-guided biliary drainage (EUS-BD), such as with EUS-guided hepaticogastrostomy (EUS-HG) [1] [2], the fistula must be dilated so that the stent delivery system can be inserted [3]. We demonstrate herein a simplified technique for performing EUS-BD with a novel fine-gauge balloon catheter (REN Biliary Dilation Catheter; Kaneka Corporation, Osaka, Japan).