tbuckley/cabot-search huggingface dataset:
Donor dendritic cell–derived exosomes promote allograft-targeting immune response
Authors: Quan Liu, Darling M. Rojas-Canales, Sherrie J. Divito, William J. Shufesky, Donna Beer Stolz, Geza Erdos, Mara L.G. Sullivan, Gregory A. Gibson, Simon C. Watkins, Adriana T. Larregina, Adrian E. Morelli
Journal: Journal of Clinical Investigation (2016)

The immune response against transplanted allografts is one of the most potent reactions mounted by the immune system. The acute rejection response has been attributed to donor dendritic cells (DCs), which migrate to recipient lymphoid tissues and directly activate alloreactive T cells against donor MHC molecules. Here, using a murine heart transplant model, we determined that only a small number of donor DCs reach lymphoid tissues and investigated how this limited population of donor DCs efficiently initiates the alloreactive T cell response that causes acute rejection. In our mouse model, efficient passage of donor MHC molecules to recipient conventional DCs (cDCs) was dependent on the transfer of extracellular vesicles (EVs) from donor DCs that migrated from the graft to lymphoid tissues. These EVs shared characteristics with exosomes and were internalized or remained attached to the recipient cDCs. Recipient cDCs that acquired exosomes became activated and triggered full activation of alloreactive T cells. Depletion of recipient cDCs after cardiac transplantation drastically decreased presentation of donor MHC molecules to directly alloreactive T cells and delayed graft rejection in mice. These findings support a key role for transfer of donor EVs in the generation of allograft-targeting immune responses and suggest that interrupting this process has potential to dampen the immune response to allografts.
Fibroblast growth factor 23 and markers of mineral metabolism in individuals with preserved renal function
Authors: Nasser A. Dhayat, Daniel Ackermann, Menno Pruijm, Belen Ponte, Georg Ehret, Idris Guessous, Alexander Benedikt Leichtle, Fred Paccaud, Markus Mohaupt, Georg-Martin Fiedler, Olivier Devuyst, Antoinette Pechère-Bertschi, Michel Burnier, Pierre-Yves Martin, Murielle Bochud, Bruno Vogt, Daniel G. Fuster
Journal: Kidney International (2016)
PD-028 Retrospective analysis of impact of Köhne prognostic category and BRAF mutation status on survival in patients with RAS wild-type metastatic colorectal cancer treated with second-line FOLFIRI with/without panitumumab
Authors: M. Peeters, S. Siena, J.-Y. Douillard, F. Rivera, J. Taieb, R. Koukakis, G. Demonty, C.-H. Köhne
Journal: Annals of Oncology (2016)
Electrocardiographic effects of nortriptyline, phenelzine, and placebo under optimal treatment conditions
Authors: A Georgotas, R E McCue, E Friedman, T B Cooper
Journal: American Journal of Psychiatry (1987)

The authors treated 44 outpatients 55 years old or older who were suffering from major depression with either nortriptyline, phenelzine, or placebo for 7 weeks. Plasma levels of nortriptyline were kept between 50 and 170 ng/ml, and platelet monoamine oxidase (MAO) inhibition in phenelzine-treated patients was kept between 70% and 80%. ECGs were compared before and after treatment. Nortriptyline produced statistically significant increases in both the heart rate and the PR interval, although none was outside the normal range. Phenelzine produced a significant decrease in the QT interval. None of the patients had pathological ECG changes under the closely monitored treatment conditions of this study.
Enquête épidémique d'infections à E. coli O157 associées à un voyage en France d'un groupe scolaire du Somerset, Angleterre
Authors: E Duffell, E Espié, T Nichols, G K Adak, H de Valk, J M Stuart
Journal: Eurosurveillance (2003)

Une etude de cohorte retrospective a ete menee apres que 2 cas confirmes et 8 cas probables d'infections a E. coli O157 verocytotoxiques aient ete depistes dans un groupe scolaire du Somerset de retour d'un voyage en France. La souche identifiee dans les 2 cas confirmes etait de type 2, lysotype 34. En depit de sa faible puissance statistique liee au petit nombre de cas, l'etude a revele que le vehicule d'infection le plus probable etait une salade de concombre (RR brut = 4,3, IC95% [0,6-29], OR ajuste = 107, IC95% indetermine, p = 0,08). Les concombres provenaient de Belgique, mais il n'a pas ete possible de retrouver leur source. La nature internationale de cette flambee souligne l'importance d'une collaboration etroite entre les organisations dans la gestion des epidemies, des normes internationales pour assurer la securite alimentaire, et d'un systeme commun de typage des souches VTEC en Europe.
Case 53-1981
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Daniel D. Federman, Eugene J. Mark
Journal: New England Journal of Medicine (1981)

Presentation of CaseA 23-year-old man was admitted to the hospital because of Cushing's syndrome.The patient was in vigorous health until one year earlier, when his parents noticed that his face appeared puffy. During the next few months, while training for a lacrosse team at his college, he observed fatigue, decreased muscle strength, and easy bruising, accompanied by a slight increase in weight. A physician found hypertension, tremor of the hands, pink striae over the buttocks, and pedal edema. Seven months before admission he entered another hospital, where the fasting 8 a.m. cortisol was 20 μg per 100 ml . . .
Controversial database of medical records is scrapped over security concerns
Authors: Matthew Limb
Journal: BMJ (2016)

The UK government has scrapped the controversial data sharing programme care.data after expert reviews called for better security provisions and new patient opt-outs for the use of personal information.

The reviews were published on 6 July by the national data guardian, Fiona Caldicott, and the Care Quality Commission (CQC).1 2

Caldicott recommended a new consent model to build public trust around sharing of confidential data and for all health and care organisations to enact 10 new data security standards.

She also recommended stronger sanctions to protect anonymised data, including criminal penalties for “deliberate and negligent re-identification of individuals.”

Caldicott highlighted concerns over data security breaches and said that she had been frustrated that there had been “little positive change” in the use of data across health and care since …
Imatinib Plus Vincristin &amp; Prednisolone Induces Complete Remission and Prolonged Survival in Elderly Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Patients.
Authors: Ashis Mukhopadhyay, Soma Mukhopadhyay, Pinaki Ranjan Gupta, Ujjal Kanti Roy, Ajoy Sinha
Journal: Blood (2007)
flt3 Ligand in Cooperation With Transforming Growth Factor-β1 Potentiates In Vitro Development of Langerhans-Type Dendritic Cells and Allows Single-Cell Dendritic Cell Cluster Formation Under Serum-Free Conditions
Authors: Herbert Strobl, Concha Bello-Fernandez, Elisabeth Riedl, Winfried F. Pickl, Otto Majdic, Stewart D. Lyman, Walter Knapp
Journal: Blood (1997)
Experience on the Application of a Commercial RT-PCR Kit on the Diagnosis of 28 Chromosomal Translocations Associated with Acute Leukemia in Adults
Authors: Lacayo-Leñero Dennis, Erick Crespo-Solís, Patricia Guzmán-Uribe, María Isabel Tussie-Luna, Maria Teresa Tusie-Luna, Adriana Rosas-López, Mabel Cerrillo-Hinojosa, Yayoi Segura-Kato
Journal: Blood (2014)
Adaptive Designs for Clinical Trials
Authors: Deepak L. Bhatt, Cyrus Mehta
Journal: New England Journal of Medicine (2016)

andomized clinical trials serve as the standard for clinical research and have contributed immensely to advances in patient care.Nevertheless, several shortcomings of randomized clinical trials have been noted, including the need for a large sample size and long study duration, the lack of power to evaluate efficacy overall or in important subgroups, and cost.These and other limitations have been widely acknowledged as limiting medical innovation. 1 Adaptive trial design has been proposed as a means to increase the efficiency of randomized clinical trials, potentially benefiting trial participants and future patients while reducing costs and enhancing the likelihood of finding a true benefit, if one exists, of the therapy being studied. 2 Adaptive designs are applicable to both exploratory and confirmatory clinical trials.Adaptive designs for exploratory clinical trials deal mainly with finding safe and effective doses or with dose-response modeling.The emphasis is on strategies that will assign a larger proportion of the participants to treatment groups that are performing well, reduce the number of participants in treatment groups that are performing poorly, and investigate a dose range that is larger than ranges in corresponding trials with nonadaptive designs, in order to select effective doses for the confirmatory stage of investigation.Control of the type I error rate is less of an issue.In Table 1, various types of adaptive designs for exploratory clinical trials are classified into categories that reflect the time sequence in which they would be performed in the drug-development process.In confirmatory trials, the adaptive nomenclature refers to making prospectively planned changes to the future course of an ongoing trial on the basis of an analysis of accumulating data from the trial itself, in a fully blinded or unblinded manner, without undermining the statistical validity of the conclusions. 3However, modifications of randomized clinical trials that are performed in an unblinded manner are subject to closer regulatory scrutiny than those performed in a blinded manner.They require careful attention to statistical techniques and operational procedures to ensure that the implementation is scientific, ethical, and free from bias.In Table 1, different types of adaptations for confirmatory trials are classified into four major categories -seamless phase 2-3 designs, sample-size reestimation, group sequential designs, and population-enrichment designs -and the strengths and weaknesses of each type are identified in relation to corresponding nonadaptive designs.There is some overlap among the different categories.For example, sample-size reestimation could be implemented on its own or incorporated into group sequential, dose-selection, or population-enrichment designs.In this review, we focus on adaptive designs of confirmatory clinical trials.We discuss the benefits and limitations of such designs, using four case studies that highlight the statistical and operational considerations that are the prerequisites
Phenformin combines with selumetinib in targeting KRAS mutant non-small cell lung cancer cells with alternative LKB1 status.
Authors: Jun Zhang, Dongsheng Wang, Guoqing Qian, Fakeng Liu, Mohammad Aminur Rahman, Sreevinas Nannapaneni, Xu Wang, Xianghong Peng, Zhuo Georgia Chen, Kwok-Kin Wong, Fadlo Raja Khuri, Wei Zhou, Dong Moon Shin
Journal: Journal of Clinical Oncology (2014)

2589 Background: Combining with docetaxel, the MEK inhibitor selumetinib holds the promise in treating KRAS mutant non-small cell lung cancer (NSCLC). However, a previous co-clinical trial based on genetically engineered mouse model (GEMM) suggested that concomitant loss of LKB1 might confer primary resistance. Since LKB1 inactivation was recently shown to sensitize NSCLC cells to the metabolism drug phenformin, which may also activate AMPK in LKB1 wild-type NSCLC, we therefore investigated whether phenformin could enhance the therapeutic effect of selumetinib in KRAS mutant NSCLC with different status of LKB1. Methods: NSCLC cell lines harboring RAS/RAF mutations that were tested with selumetinib were identified from literature to study the correlation of LKB1 status with selumetinib sensitivity. Then, the isogenic derivatives of A549 cell line namely A549LKB1 (stably expressing wild-type LKB1) and A549pBabe (empty vector, LKB1 deficient) were used for actual studies of selumetinib, phenformin, their combination and dosing sequence. Phenformin was also investigated in GEMM derived cell lines 634 (KrasG12D/wt/p53-/-/LKB1wt/wt) and t2 (KrasG12D/wt/p53-/-/LKB1-/-). Results: 29 NSCLC cell lines were identified which showed concomitant LKB1 mutation significantly correlated with selumetinib resistance (IC50>1uM, p=0.0025). Consistently, A549LKB1 cells were more sensitive to selumetinib. In contrast, A549pBabe (as well as t2) cells showed stronger response to phenformin. Their synergism was observed in both the proliferation and colony formation assays, and confirmed via CalcuSyn calculation. While phenformin helped induce much more robust apoptosis in A549pBabe cells, it also activated AMPK and potently enhanced the inhibition of S6 phosphorylation by selumetinib in A549LKB1cells. Interestingly, when the drugs were applied sequentially in single agent, selumetinib followed by phenformin was ~ 3 folds more efficient in inducing apoptosis than the reverse order. Conclusions: Phenformin may synergize the anti-tumor effect of selumetinib in KRAS mutant NSCLC irrespective of the LKB1 status. Their combination offers a potential new therapy for this subtype of NSCLC.
Elotuzumab for the treatment of multiple myeloma
Authors: Yucai Wang, Larysa Sanchez, David S. Siegel, Michael L. Wang
Journal: Journal of Hematology & Oncology (2016)

Elotuzumab is one of the first two monoclonal antibodies that gained FDA approval for the treatment of multiple myeloma (MM). It targets SLAMF7, which is highly expressed in normal plasma and MM cells as well as natural killer (NK) cells. Elotuzumab demonstrated significant anti-myeloma activity in preclinical studies, and its mechanisms of action include mediating antibody-dependent cell-mediated cytotoxicity, enhancing cytotoxicity of NK cells, and inhibiting MM cell interaction with bone marrow stromal cells. In clinical trials, elotuzumab in combination with immunomodulatory drugs and proteasome inhibitors has demonstrated an excellent efficacy and safety profile in treating MM.
Interim Analysis Of The Mmrf Commpass Trial, a Longitudinal Study In Multiple Myeloma Relating Clinical Outcomes To Genomic and Immunophenotypic Profiles
Authors: Jonathan J Keats, David W Craig, Winnie Liang, Yellapantula Venkata, Ahmet Kurdoglu, Jessica Aldrich, Daniel Auclair, Kristi Allen, Beverly Harrison, Scott Jewell, Pamela G. Kidd, Mick Correll, Sundar Jagannath, David S. Siegel, Ravi Vij, Gregory Orloff, Todd M. Zimmerman, Walter Capone, John Carpten, Sagar Lonial
Journal: Blood (2013)
The missing era of breast cancer chemotherapy.
Authors: E M Greenspan
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.3.565 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2307993 The missing era of breast cancer chemotherapy. E M GreenspanxE M GreenspanSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.3.565 PDF "The missing era of breast cancer chemotherapy.." Journal of Clinical Oncology, 8(3), p. 565© 1990 by American Society of Clinical Oncology
Case 27-1978
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Ashby C. Moncure, Karl H. Proppe
Journal: New England Journal of Medicine (1978)

Presentation of Case First admission. A 78-year-old man was admitted to the hospital because of a pulmonary lesion.He was well until four years earlier, when he began to have exertional angina pectoris, which progressed until it occurred on climbing one flight of stairs. Intermittent claudication developed. Three months before admission he began to experience an aching pain in the right anterior hemithorax that was occasionally pleuritic, with frequent "feverish" sensations and drenching night sweats. Several weeks before entry a dry cough developed. The chest pain gradually improved, although occasional pain about the right shoulder occurred. Ten days before admission . . .
Need randomized clinical trials, not litigation.
Authors: D S Fischer
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.3.1237 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9508216 Need randomized clinical trials, not litigation. D S FischerxD S FischerSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.3.1237 PDF "Need randomized clinical trials, not litigation.." Journal of Clinical Oncology, 16(3), pp. 1237–1238© 1998 by American Society of Clinical Oncology
Structural and functional abnormalities in the spleen of an mFtz-F1 gene-disrupted mouse
Authors: Ken ichirou Morohashi, Hisae Tsuboi-Asai, Sumie Matsushita, Masahiro Suda, Manabu Nakashima, Hironobu Sasano, Yoshiaki Hataba, Chun Li Li, Junichi Fukata, Junji Irie, Takeshi Watanabe, Hiroshi Nagura, En Li
Journal: Blood (1999)
Coagulation Activation By Heme: Evidence from Global Hemostasis Assays
Authors: Gleice Regina Souza, Maiara M L Fiusa, Carolina Lanaro, Marina Pereira Colella, Silmara A L Montalvao, Sara T O Saad, Fernando Ferreira Costa, Fabiola Traina, Joyce M Annichino-Bizzacchi, Erich Vinicius De Paula
Journal: Blood (2014)
Case 19-1964
Authors: Claude E. Welch, Benjamin Castleman
Journal: New England Journal of Medicine (1964)

Presentation of Case First admission. A fifty-nine-year-old woman was admitted to the hospital because of a mass in the abdomen.She had been in good health until eleven years previously, when she entered another hospital because of a productive cough, fever and night sweats. Examination revealed rales medial to the left scapula and a movable oval mass, approximately 5 cm. in greatest diameter, to the right of the umbilicus. X-ray films of the chest showed pleural thickening on the right side, atelectasis at the base of the right lung and an infiltrate in the right-middle-lung field; films of the gastrointestinal . . .
Letter to the editor: Influenza vaccine effectiveness: heterogeneity in estimates for the 2012/13 season
Authors: W van der Hoek, F Dijkstra, M M de Lange, G A Donker, A Meijer, M A van der Sande
Journal: Eurosurveillance (2013)

Preview this article: Letter to the editor: Influenza vaccine effectiveness: heterogeneity in estimates for the 2012/13 season, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/18/7/art20399-en-1.gif
PD-026 Survival outcomes in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) classified by Köhne prognostic category and BRAF mutation status: retrospective analysis of the PRIME study
Authors: C.-H. Köhne, F. Rivera, J. Taieb, S. Siena, M. Peeters, R. Koukakis, G. Demonty, J.-Y. Douillard
Journal: Annals of Oncology (2016)
Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives
Authors: Juan P. Arab, Saul J. Karpen, Paul A. Dawson, Marco Arrese, Michael Trauner
Journal: Hepatology (2016)

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches to prevent disease progression to advanced fibrosis or cirrhosis and cancer. In recent years, bile acids have emerged as relevant signaling molecules that act at both hepatic and extrahepatic tissues to regulate lipid and carbohydrate metabolic pathways as well as energy homeostasis. Activation or modulation of bile acid receptors, such as the farnesoid X receptor and TGR5, and transporters, such as the ileal apical sodium-dependent bile acid transporter, appear to affect both insulin sensitivity and NAFLD/NASH pathogenesis at multiple levels, and these approaches hold promise as novel therapies. In the present review, we summarize current available data on the relationships of bile acids to NAFLD and the potential for therapeutically targeting bile-acid-related pathways to address this growing world-wide disease. (Hepatology 2017;65:350-362).
P-034 The potential of extravasated platelet aggregation as a surrogate marker for overall survival in patients with advanced gastric cancer treated by preoperative docetaxel, cisplatin, and S-1
Authors: S. Fushida, H. Saito, T. Kurata, J. Kinoshita, K. Oyama, T. Miyashita, T. Ohta
Journal: Annals of Oncology (2016)
Study Program Aims to Define Growth Factors; Heart Disease, Pituitary Deficiency Are Lead
Authors: V KNIGHT, W F FLEET, D J LANG
Journal: JAMA (1964)

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