tbuckley/cabot-search huggingface dataset:
Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer
Authors: Haijun Yu, Chengyue Guo, Bing Feng, Jianping Liu, Xianzhi Chen, Dangge Wang, Lesheng Teng, Youxin Li, Qi Yin, Zhiwen Zhang, Yaping Li
Journal: Theranostics (2015)

The combination of chemotherapy and RNA interference is a promising approach for efficient cancer therapy. However, the success of such a strategy is hampered by the lack of suitable vectors to coordinate small interfering RNA (siRNA) and chemotherapeutic drug into one single platform. We herein report a novel triple-layered pH-responsive micelleplex loading siRNA and alkylated cisplatin prodrug for NF-Kappa B targeted treatment of metastatic breast cancer. The micelles were self-assembled from poly(ethylene glycol)-block-poly(aminolated glycidyl methacrylate)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-b-PAGA-b-PDPA) triblock copolymers. At pH 7.4, the cisplatin prodrug was encapsulated in the hydrophobic PDPA core and siRNA was loaded on the positively charged PAGA interlayer to form the micelleplexes. The PEG corona can prevent protein absorption during blood circulation, minimize non-specific interaction with the reticuloendothelial system, and prolong the systemic circulation of the micelleplexes. The positively charged PAGA interlayer can facilitate deep tumor penetration of the micelleplexes, which, upon cellular uptake, are dissociated in the early endosomes to release anticancer drug payload due to protonation of the PDPA core. Using a 4T1 breast cancer model, we demonstrate that this novel micelleplex co-loaded with cisplatin prodrug and siRNA-p65 is able to simultaneously inhibit tumor growth and suppress distant metastasis of the cancer cells by downregulating NF-kappa B expression. The results reported in this study suggest that siRNA and anticancer drug co-delivery using pH-responsive micelleplexes is a promising strategy for efficient treatment of metastatic cancer.
<i>Deleted in cancer 1</i>: Search for a function in prostate cancer
Authors: J. Hirsch, T. Nelius, C. Pfarr, W. De Riese, I. Wieland, S. Filleur
Journal: Journal of Clinical Oncology (2009)

e16095 Background: Deleted In Cancer 1 (DICE1/INTS6) gene was recently identified to colocalize with the microsatellite marker D13S284 in 13q14.3, a region frequently affected by allelic deletion in many solid tumors including prostate cancer (PrCa). DICE1 missense mutations have been previously detected in PrCa cell line LNCap, and reduced DICE1 expression appears to be associated with CpG promoter hypermethylation in PrCa cells. DICE1 is a highly conserved nuclear protein suggesting its involvement in DNA repair, transcription, or RNA splicing. In mouse, the DICE1 homologue interferes with the response to insulin-like growth factor 1 and suppresses anchorage-independent growth of transformed mouse cells. The totality of these results suggests that DICE1 is a tumor suppressor gene and insist on the need to better characterize DICE1 function in PrCa. Methods: Expression of DICE1 was evaluated by Northern Blot in PrCa cell lines LNCap, DU145, PC3, PC3ml and CPTX1532 and compared to expression level in normal prostate cell line NPTX1532. DICE1 growth inhibitory effects were analyzed by colony formation assay on PC3 and DU145 cells transfected with DICE1 expression plasmid or control vector. Apoptosis was assessed by visualization of genomic DNA fragmentation on agarose gel. PCR arrays (SABiosciences) were used to identify specific signaling pathways modulated in response to DICE1 expression. Results: Markedly decreased DICE1 mRNA levels were detected in PrCa cell lines LNCap, DU145, PC3 and PC3ml as well as CPTX1532 as compared to NPTX1532, a cell line derived from normal prostate tissue. Ectopic expression of DICE1 cDNA in DU145 and PC3 cells substantially suppressed their ability to form colonies in vitro. This growth inhibition was not due to immediate induction of apoptosis suggesting growth suppression by other pathways. Expression profiling identified multiple pathways, such as Wnt, Hedgehog, PI-3 Kinase, NFκB and Insulin pathways, regulated in response to ectopic DICE1 expression. Furthermore, various transcription factors including Fos, Jun, CEBPA and PPAR-γ were up-regulated in response to DICE1. Conclusions: These results clearly illustrate the growth inhibitory ability of DICE1 in PrCa. Expression profiling links DICE1 function to growth factor signaling and cell-cell communication. No significant financial relationships to disclose.
Response assessment of HCC undergoing chemoembolization by necrosis-adjusted models
Authors: M. A. Rosen, A. Ruutiainen, E. Siegelman, L. Jones, W. Sun, R. Reddy, A. Shaked, K. Olthoff, M. Soulen
Journal: Journal of Clinical Oncology (2009)

e15528 Background: Chemoembolization (CE) is an accepted therapy for unresectable HCC. As treated tumors may not shrink in size, response assessment via measurement of the enhancing tumor (EASL) has been proposed as an alternate to whole tumor (RECIST) measures. However, the reliability of this model has not been tested in clinical practice. Methods: We identified 29 HCC patients treated with CE with known overall survival (OS) in whom MRI before and after initial CE therapy was available for review. Three radiologists evaluated the imaging, measuring the largest liver lesion in three dimensions and the largest enhancing region in two dimensions. Readers also assessed percent tumor necrosis and overall tumor response qualitatively. Response models in 1-, 2-, or 3- dimensions, with or without necrosis adjustment, were created to assign patients to CR/PR/SD/PD classes, based on majority classification. Predictive value for OS was assessed for PD vs. other, and for PR/CR vs. SD/PD by the Students’ t-test. Inter-reader concordance was assessed by the Fleiss κ statistic. Results: For non-necrosis adjusted models, OS for progressors vs. non-progressors was statistically significant (p values: 0.0002–0.04), but could not identify early responders. Necrosis adjusted models failed to identify early progressors, but identified responders with improved OS (p values: 0.02–0.12). Inter-reader concordance was higher for necrosis adjusted models (κ range: 0.36–0.52) than for non-necrosis adjusted models (0.16–0.23). Viable tumor response by a two-dimensional product was superior to a one-dimensional diameter for predicting OS (p=0.04 vs. 0.74), and demonstrated higher inter-reader concordance (κ=0.46 vs. 0.30). Qualitative assessment of hepatic tumor could predict differences in OS for both PD vs. others (p=0.0001) and responders vs. non-responders (p=0.04), with acceptable inter-reader concordance (κ=0.34). Conclusions: Two- dimensional, but not one-dimensional, viable tumor measurement can identify response of HCC to chemoembolization and predict OS. Models which incorporate qualitative reader assessment of tumor necrosis may be more flexible than direct measures of viable tumor, and should be considered as alternatives for tumor assessment in chemoembolization. No significant financial relationships to disclose.
Abstract 15727: Analyzing Unstructured Clinical Notes for Phase IV Drug Safety Surveillance
Authors: Paea LePendu, Anna Bauer-Mehren, Srinivasan Iyer, Nigam H Shah
Journal: Circulation (2012)

Background:  The current state of the art in post-marketing drug surveillance utilizes large collections of submitted reports to detect adverse drug reactions. However, given the limitations of reporting systems, there is an opportunity to meaningfully use electronic health records (EHRs) for next-generation signal detection and advancement of drug safety surveillance.   Methods and Results:  We present data mining methods that transform unstructured patient notes taken by doctors, nurses and other clinicians into a de-identified, temporally ordered, patient-feature matrix using standardized medical terminologies. We demonstrate how to use the resulting high-throughput data to monitor for adverse drug events based on the clinical notes in the EHR. We analyze the patterns of mentions of disease conditions, drug names, their co-mentions and the temporal ordering of the drugs and diseases, in the output of our text processing pipeline to detect known associations between drugs and their adverse effects. Overall, our methods provide highly accurate results (72% Sensitivity, 83% Specificity) as measured by testing a set of 25 known drug recalls and a set of 200 “true negative” drug-adverse event associations. We are able to detect associations between a drug and the adverse event that results in its recall, on average, 2 years ahead of the official notification. We also describe methods for investigating a suspect drug-adverse event association using stratification, propensity score matching and show that matching based on co-morbidities and co-prescriptions may correct for confounding from unobserved variables; thus making the data-mining methods robust against confounding.   Conclusion:  We conclude that data-mining of unstructured clinical notes via ontology driven methods can enable meaningful use of the EHR for post-marketing drug surveillance. Such data-mining can be used for hypothesis generation and for rapid retrospective analysis of suspected adverse event risk.
The effect of specific and nonspecific immunotherapy on natural killer cell activity in patients with non-small-cell lung cancer.
Authors: J A Maroun, H F Pross, T H Stewart, M J White, D B Hyslop
Journal: Journal of Clinical Oncology (1984)

Fourteen patients with stages I and II non-small-cell lung carcinoma receiving adjuvant immunotherapy after surgery were studied serially for natural killer (NK) cell cytotoxicity assays. Seven patients received active nonspecific immunotherapy with Freund's complete adjuvant alone and seven patients received active specific immunotherapy with tumor-associated antigen plus Freund's complete adjuvant. Both groups were analyzed as a single group in view of the lack of any difference in the results. The results indicated that NK-cell cytotoxicity v K562 was lower in untreated patients than in normal controls, but the difference was not significant. There was no evidence of specific cytotoxicity v the lung cell line A549 in untreated patients when compared with normal controls. Compared with pretreatment values, elevated cytotoxicity v both K562 and A549 was observed at every post-treatment time point tested, and this was statistically significant at several time points by a paired t test. No specific effect was noted after immunization with lung antigen on cytotoxicity against the lung cell line A549. Other correlations studied did not show any relationship between delayed hypersensitivity skin testing or serum carcinoembryonic antigen levels and NK-cell cytotoxicity. It is concluded that NK-cell reactivity was increased nonspecifically by active specific and nonspecific immunotherapy. This increase seems to peak at the 12-month period and was significant when compared with pretreatment levels.
Prognosis of Brief Psychotic Episodes
Authors: Paolo Fusar-Poli, Marco Cappucciati, Ilaria Bonoldi, L. M. Christy Hui, Grazia Rutigliano, Daniel R. Stahl, Stefan Borgwardt, Pierluigi Politi, Aaron L. Mishara, Stephen M. Lawrie, William T. Carpenter, Philip K. McGuire
Journal: JAMA Psychiatry (2016)

The prognostic significance of competing constructs and operationalizations for brief psychotic episodes (acute and transient psychotic disorder [ATPD], brief psychotic disorder [BPD], brief intermittent psychotic symptoms [BIPS], and brief limited intermittent psychotic symptoms [BLIPS]) is unknown.To provide a meta-analytical prognosis of the risk of psychotic recurrence in patients with remitted first-episode ATPD, BPD, BIPS, and BLIPS and in a benchmark group of patients with remitted first-episode schizophrenia (FES). We hypothesized a differential risk: FES > ATPD > BPD > BIPS > BLIPS.The Web of Knowledge and Scopus databases were searched up to May 18, 2015; the articles identified were reviewed as well as citations of previous publications and results of a manual search of the reference lists of retrieved articles.We included original articles that reported the risk of psychotic recurrence at follow-up for patients in remission from first-episode ATPD, BPD, BLIPS, BIPS, and FES.Independent extraction by multiple observers. Random-effects meta-analysis was performed, and moderators were tested with meta-regression analyses, Bonferroni corrected. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results. Publication bias was assessed with funnel plots and the Egger test.Proportion of patients with baseline ATPD, BPD, BLIPS, and BIPS who had any psychotic recurrence at 6, 12, 24, and 36 or more months of follow-up.Eighty-two independent studies comprising up to 11,133 patients were included. There was no prognostic difference in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS at any follow-up (P > .03). In the long-term analysis, risk of psychotic recurrence (reported as mean [95% CI]) was significantly higher in the FES group (0.78 [0.58-0.93] at 24 months and 0.84 [0.70-0.94] at ≥ 36 months; P < .02 and P < .001, respectively) compared with the other 4 groups (0.39 [0.32-0.47] at 24 months and 0.51 [0.41-0.61] at ≥ 36 months). There were no publication biases. Sex and exposure to antipsychotic medication modulated the meta-analytical estimates (.002 < P < .03).There are no prognostic differences in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS constructs of brief psychotic episodes. Conversely, there is consistent meta-analytical evidence for better long-term prognosis of brief psychotic episodes compared with remitted first-episode schizophrenia. These findings should influence the diagnostic practice and clinical services in the management of early psychosis.
Descending Aorta Rupture During Transcatheter Aortic Valve Replacement
Authors: Jose Alberto de Agustin, Pilar Jiménez-Quevedo, Luis Nombela-Franco, Carlos Almeria, José Juan Gomez de Diego, Jose Luis Rodrigo, Pedro Marcos-Alberca, Patricia Mahia, Ivan Javier Nuñez-Gil, Leopoldo Perez de Isla, Antonio Fernandez-Ortiz, Carlos Macaya
Journal: Circulation (2016)
Peripheral Blood Mononuclear Cells Induce Programmed Cell Death in Human Endothelial Cells and May Prevent Repair: Role of Cytokines
Authors: Heidrun Lindner, Ernst Holler, Birgit Ertl, Gabriele Multhoff, Manuela Schreglmann, Ines Klauke, Susanne Schultz-Hector, Günther Eissner
Journal: Blood (1997)
Randomized Comparison of Percutaneous Repair and Surgery for Mitral Regurgitation
Authors: Ted Feldman, Saibal Kar, Sammy Elmariah, Steven C. Smart, Alfredo Trento, Robert J. Siegel, Patricia Apruzzese, Peter Fail, Michael J. Rinaldi, Richard W. Smalling, James B. Hermiller, David Heimansohn, William A. Gray, Paul A. Grayburn, Michael J. Mack, D. Scott Lim, Gorav Ailawadi, Howard C. Herrmann, Michael A. Acker, Frank E. Silvestry, Elyse Foster, Andrew Wang, Donald D. Glower, Laura Mauri
Journal: Journal of the American College of Cardiology (2015)
TNF-αに誘発される上皮間葉転換はTwist1のNF-κB-介在転写上方制御を必要とする
Authors: LI Chia-Wei, Xia Weiya, Huo Longfei, Lim Seung-Oe, Wu Yun, L Hsu Jennifer, Chao Chi-Hong, Yamaguchi Hirohito, Yang Neng-Kai, Ding Qingqing, Wang Yan, Lai Yun-Ju, M Labaff Adam, WU Ting-Jung, Lin Been-Ren, Yang Muh-Hwa, N Hortobagyi Gabriel, Hung Mien-Chie
Journal: Cancer Research (2012)
Doctor-patient hierarchy may have a therapeutic role
Authors: Dror Limon, Salomon M Stemmer
Journal: BMJ (2015)

Use of the title “Doctor” preserves hierarchy in a patient-doctor relationship.1 However, hierarchy does not necessarily mean lack of respect, and deferential status exists in the patient-doctor relationship, regardless of whether this term is used. A similar hierarchy and relationship exist when we consult a priest, imam, rabbi, or any …
Molecular Profiling of Small Intestinal Neuroendocrine Tumours
Authors: A. Karpathakis, A. Feber, T. Morris, H. Dibra, C. Pipinikas, D. Oukrife, J. Francis, D. Mandair, C. Toumpanakis, T. Meyer, T.V. Luong, M. Caplin, M. Meyerson, S. Beck, C. Thirlwell
Journal: Annals of Oncology (2014)
Self rated "health score" can predict risk of death in next five years, researchers say
Authors: M. Limb
Journal: BMJ (2015)

Researchers have developed a score calculated from self reported information that predicts the risk of death within five years for UK people aged between 40 and 70. But some scientists have questioned its practical value and have said that the researchers’ claims that it could be of major benefit to people, influence health policy, and add to clinicians’ knowledge may be overstated.

A Swedish study showing how the score was developed from an analysis of data in the UK Biobank and how people could calculate their own five year death risk online was published in the Lancet on 4 June.1 One of the coauthors, Andrea Ganna, a research fellow at Stockholm’s Karolinska Institute, said that enabling people to estimate their personalised risk without any need for laboratory tests or physical examinations was an “exciting development.”

He and Erik Ingelsson, a professor of molecular epidemiology at Uppsala University, analysed UK Biobank data collected …
Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial
Authors: Andrew J Armstrong, Susan Halabi, Tim Eisen, Samuel Broderick, Walter M Stadler, Robert J Jones, Jorge A Garcia, Ulka N Vaishampayan, Joel Picus, Robert E Hawkins, John D Hainsworth, Christian K Kollmannsberger, Theodore F Logan, Igor Puzanov, Lisa M Pickering, Christopher W Ryan, Andrew Protheroe, Christine M Lusk, Sadie Oberg, Daniel J George
Journal: The Lancet Oncology (2016)
Autologous Stem Cell Transplantation Using BEAM Conditioning Is Highly Effective in Patients with Follicular Lymphoma Regardless of Prior Rituximab Exposure
Authors: Jaimal Kothari, Antonia Ljubic, Karl S Peggs, Kirsty Thomson, Emma Morris, Andres E. Virchis, Jonathan Lambert, Anthony H Goldstone, David C Linch, Kirit M Ardeshna
Journal: Blood (2011)
Impact of use of hormone replacement therapy on false positive recall in the National Health Services Breast Screening Programme: population-based prospective study
Authors: Emily Banks, Gillian K Reeves, Valerie Beral, Diana Bull, Barbara Crossley, Moya Simmonds, Elizabeth Hilton, Stephen Bailey, Nigel Barrett, Peter Briers, Ruth English, Alan Jackson, Elizabeth Kutt, Janet Lavelle, Linda Rockall, Matthew G Wallis, Mary Wilson, Julietta Patnick
Journal: BMJ (2004)
Escalation of therapy without evidence: a “may” does not imply a “should”!
Authors: M. Heringlake, B. Bein, M. Buerke, D. Damjanovic, H. Ebelt, H. V. Groesdonk, A. Markewitz, M. Möckel, R. Moosdorf, K. Pilarczyk, D. A. Reuter, M. Sander, A. Schmitt, G. Trummer, S. Treskatsch, M. Von der Brelie, B. Zante, A. Zarbock, N. Haake
Journal: Intensive Care Medicine (2016)
Soundings: Do you believe in God?
Authors: Kevin Barraclough
Journal: BMJ (1999)

As he left the consulting room he turned.

“Do you believe in God?” he asked.

He was a man in his 40s with two young children and prostate cancer.

I don’t think that I answered.

He didn’t, he said.

The terminal care went well until the end. But he was young, and his bodily systems did not fade gracefully as with older patients. He was restless and inadequately sedated at the end, probably through my inexperience.

He would half rise from the bed, shouting, “Midnight, darkness, death.” We were privy to the echoes from his tortured mind. It was a disturbing experience for his wife, his young children, and our district nurse. In the end we had to transfer him to hospital and he died there.

My experiences with believers have been different. I think of the slow death of a monk in our local monastery. It was serene and peaceful.

What about the medical carers? Does their faith or lack of it make a difference? I am not aware of any evidence on the subject, although I would be surprised if there was none.

Those events have stayed with me for some years, haunting those occasional sleepless hours before dawn. I learnt much later that my colleague, our district nurse, had sought professional help after the experience. It never occurred to me to do the same—a reflection, perhaps, of the way that we treat ourselves as a profession.

I can’t recall now why I didn’t answer my patient when he asked me whether I believed in God. I think it was partly surprise. Also, perhaps, the stumbling qualification you feel with the dying, searching to see if you are saying the right thing in the right way.

But also, in the end, it was the massive imprecision of the terminology. Do you mean the same as I do by the question?

I am reminded of the story of the erudite theologian who was sometimes suspected by the zealots of heresy. A journalist confronted him.

“Do you believe in God?” he asked.

The theologian eyed him cautiously. “I can answer you,” he said, “but the answer is complex, and I can promise you that you will not understand my answer. Do you want me to go ahead?”

“Certainly.”

“All right. The answer is yes.”
Pediatric Antimicrobial Discharge Stewardship
Authors: Adam L. Hersh, Jason G. Newland, Jeffrey S. Gerber
Journal: JAMA Pediatrics (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 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
The eligibility of women for clinical research trials.
Authors: W B Patterson, E J Emanuel
Journal: Journal of Clinical Oncology (1995)

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.1995.13.1.293 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7799033 The eligibility of women for clinical research trials. W B PattersonxW B PattersonSearch for articles by this author , E J EmanuelxE J EmanuelSearch for articles by this author Show More Dana-Farber Cancer Institute, Boston, MA 02115. https://doi.org/10.1200/JCO.1995.13.1.293 First Page PDF © 1995 by American Society of Clinical OncologyKeywords: Biomedical and Behavioral ResearchDana-Farber Cancer Institute (Boston)... Show All
Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes
Authors: Adil Mardinoglu, Jan Boren, Ulf Smith
Journal: Cell Metabolism (2016)

Type 2 diabetes (T2D) is associated with dysbiosis of the gut microbiota, though diabetes treatment regimens, including metformin, may confound the results. Forslund et al. (2015) identify distinct disease and drug signatures and highlight the importance of adjusting for treatment when investigating how T2D influences the human gut microbiome.