tbuckley/cabot-search huggingface dataset:
Co-trimoxazole prophylaxis during high-dose chemotherapy of small-cell lung cancer.
Authors: A T Figueredo, W M Hryniuk, I Strautmanis, G Frank, S Rendell
Journal: Journal of Clinical Oncology (1985)

In 103 patients with small-cell lung cancer, we compared four courses of standard doses of Adriamycin (A) (Adria Laboratories, Columbus, Ohio), vincristine (V), and cyclophosphamide (C) with a regimen of increased doses of cyclophosphamide and to a lesser extent, Adriamycin. We found no significant difference in rate (22% v 21%) or median duration (seven v nine months) of complete remission. Patients not in complete remission after the four cycles of AVC received two courses of VP-16 (etoposide) and cisplatin: the complete remission rate increased to 49% and 48% respectively. Patients on the high-dose arm received co-trimoxazole prophylaxis; those on the standard arm did not. Patients on the high-dose arm had a higher incidence of neutropenia (nadir less than 500 cells/microL) but a lower incidence of infection for similar degrees of neutropenia. However, they also suffered more severe side effects of a different kind. Cotrimoxazole thus allowed for the administration of higher doses of chemotherapy to outpatients by protecting them from infection. However, the higher doses of cyclophosphamide and Adriamycin, did not improve treatment results, produced more severe side effects, and is not recommended.
HIC1 is a new E2F1 transcriptional target involved in cell death
Authors: Mathias Jenal, Emmanuelle Trinh, Christian Britschgi, Anne-Catherine Andres, Dominique Leprince, Kristian Helin, Martin F. Fey, Andreas Tobler, Mario P. Tschan
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4504 

The HIC1 gene (Hypermethylated in Cancer 1) located on chromosome 17 encodes for a transcription factor with five zinc fingers, and an amino-terminally located BTB/POZ repression domain. It chiefly acts as a transcriptional repressor that functionally cooperates with p53 to suppress cancer development. Recently it was shown that inactivation of HIC1 results in upregulated SIRT1, a deacetylase which inactivates p53, allowing cells to bypass apoptosis. Furthermore, we and others showed that HIC1 is a transcriptional target of p53, forming a positive feedback loop.

In an attempt to identify new transcriptional regulators of HIC1 we screened a human HIC1 promoter reporter construct for activation by a set of transcription factors. We identified the transcription factor E2F1 as a strong activator of the full-length HIC1 promoter reporter. Co-transfection of the HIC1 promoter reporter with E2F1 showed a 22-fold induction as compared with the empty vector control. Promoter deletion and mutation constructs identified two E2F responsive elements in the HIC1 promoter region. Mutation of either E2F binding site in the HIC1 promoter significantly reduced the response to E2F1. Moreover, binding of E2F1 to the endogenous HIC1 promoter was shown by chromatin immunoprecipitation assays in normal human TIG3 fibroblasts expressing tamoxifen-inducible E2F1.

Upon activation of E2F1 in TIG3 cells, we found an 11-fold increase of endogenous HIC1 mRNA compared with non-induced control cells. Interestingly, this effect was not seen in U2OS cancer cells upon E2F1 activation most likely since in this cell line the HIC1 promoter is hypermethylated. In line with this hypothesis we found that treating U2OS cells with the demethylating agent 5-aza-2’-deoxycytidine increased HIC1 mRNA levels 7-fold. In addition, shRNA-mediated knock-down of HIC1 in TIG3 cells significantly reduced E2F1-induced cell death compared with cells expressing a control shRNA as shown by tetrazolium salt reduction assays. TIG3 cells with knocked-down p53 were used as control for reduced cell death upon E2F1 activation.

E2F1 can induce cell cycle progression as well as cell death. The latter is caused by dysregulated E2F1 expression and is seen as tumor suppressor mechanism. We identified E2F1 as transcriptional activator of HIC1 and propose that E2F1-induced cell death occurs partially via induction of HIC1. Subsequently, elevated HIC1 levels might suppress the p53 negative regulator SIRT1 allowing for higher p53 activity. The newly found E2F1-HIC1 network delineates yet another E2F1-induced cell death pathway.
Heart Failure in Ethnic Minorities
Authors: Ileana L. Piña, Hector O. Ventura
Journal: JACC Heart Failure (2014)

“No Chinese will leave his home to seek his fortune at a distance unless he is in some way driven to do so… No Chinese leaves his home not intending to return. His hope is always to come back rich, to die and be buried where his ancestors are buried.” —A.H. Smith [(1)][1]

The fast increase
Erratum: Corrigendum: Common variants at 19p13 are associated with susceptibility to ovarian cancer
Authors: Kelly L Bolton, Jonathan Tyrer, Honglin Song, Susan J Ramus, Maria Notaridou, Chris Jones, Tanya Sher, Aleksandra Gentry-Maharaj, Eva Wozniak, Ya-Yu Tsai, Joanne Weidhaas, Daniel Paik, David J Van Den Berg, Daniel O Stram, Celeste Leigh Pearce, Anna H Wu, Wendy Brewster, Hoda Anton-Culver, Argyrios Ziogas, Steven A Narod, Douglas A Levine, Stanley B Kaye, Robert Brown, Jim Paul, James Flanagan, Weiva Sieh, Valerie McGuire, Alice S Whittemore, Ian Campbell, Martin E Gore, Jolanta Lissowska, Hanna P Yang, Krzysztof Medrek, Jacek Gronwald, Jan Lubinski, Anna Jakubowska, Nhu D Le, Linda S Cook, Linda E Kelemen, Angela Brooks-Wilson, Leon F A G Massuger, Lambertus A Kiemeney, Katja K H Aben, Anne M van Altena, Richard Houlston, Ian Tomlinson, Rachel T Palmieri, Patricia G Moorman, Joellen Schildkraut, Edwin S Iversen, Catherine Phelan, Robert A Vierkant, Julie M Cunningham, Ellen L Goode, Brooke L Fridley, Susan Kruger-Kjaer, Jan Blaeker, Estrid Hogdall, Claus Hogdall, Jenny Gross, Beth Y Karlan, Roberta B Ness, Robert P Edwards, Kunle Odunsi, Kirsten B Moyisch, Julie A Baker, Francesmary Modugno, Tuomas Heikkinenen, Ralf Butzow, Heli Nevanlinna, Arto Leminen, Natalia Bogdanova, Natalia Antonenkova, Thilo Doerk, Peter Hillemanns, Matthias Dürst, Ingo Runnebaum, Pamela J Thompson, Michael E Carney, Marc T Goodman, Galina Lurie, Shan Wang-Gohrke, Rebecca Hein, Jenny Chang-Claude, Mary Anne Rossing, Kara L Cushing-Haugen, Jennifer Doherty, Chu Chen, Thorunn Rafnar, Soren Besenbacher, Patrick Sulem, Kari Stefansson, Michael J Birrer, Kathryn L Terry, Dena Hernandez, Daniel W Cramer, Ignace Vergote, Frederic Amant, Diether Lambrechts, Evelyn Despierre, Peter A Fasching, Matthias W Beckmann, Falk C Thiel, Arif B Ekici, Xiaoqing Chen, Sharon E Johnatty, Penelope M Webb, Jonathan Beesley, Stephen Chanock, Montserrat Garcia-Closas, Tom Sellers, Douglas F Easton, Andrew Berchuck, Georgia Chenevix-Trench, Paul D P Pharoah, Simon A Gayther
Journal: Nature Genetics (2015)
P0657 : Adding tenofovir to Pegylated Interferon enhances end of treatment HBsAg loss in HBeAg negative chronic hepatitis B patients
Authors: P. Marcellin, M. Martinot Peignoux, R. Moucari, M. Lapalus, C. Castelnau, F. Mouri, M. Pouteau, N. Giuliy, N. Boyer, T. Asselah
Journal: Journal of Hepatology (2015)
Linking diet, religion and cancer
Authors: S. P. Yadav, A. Sachdeva
Journal: Journal of Clinical Oncology (2007)

21172 Background: Consumption of onion and garlic has been shown to give protection against various cancers. Motivated by this observation we intended to look at the cancer incidence in a population belonging to Jain religion that does not consume garlic and onion due to religious belief. This study was done to see cancer incidence in children of Jain religion as compared to other religions at a single centre. Methods: It was a retrospective analysis of consecutive children less than 16 years of age diagnosed with cancer at Sir Ganga Ram Hospital from January 2005 to January 2007. We excluded adult patients with cancer as tobacco and alcohol consumption in this age group would have been confounding factors.Age, sex and religion were noted. Data from Census of India for year 2001 was used to know distribution of various religions in general population alongwith literacy rates and proportion in 0–6 years age. Results: As per 2001 Census of India , distribution of population in India as per various religions is Hindu 80.5%, Muslim 13.4%, Christian 2.3%, Sikh 1.9%, Buddhist 0.8% , Jain 0.4% and others 0.6%. Proportion of population in 0–6 year of age in India is 15.9% and as per religions Hindu 15.6%, Muslim 18.7% ,Christian 13.5%, Sikh 12.8%, Buddhist 14.4% and Jain 10.6%. Literacy rates of India is 64.5% and by religion is Hindu 65%, Muslim 59.1% Christian 80.3%, Sikh 69.4%, Buddhist 72.7% and Jain 94%. Distribution of population in Delhi as per various religions is Hindu 82%, Muslim 11.7%, Christian 0.9%, Sikh 4%, Buddhist 0.2% and Jain 1%. Total of 201 patients were diagnosed with cancer and distribution as per religions was Hindu 162 (81%), Muslim 15 (7.5%), Christian 3 (1.5%), Sikh 8 (4%), Buddhist 1 (0.05%) and Jain 12 (6%). Conclusions: Incidence of cancer in children of different religions is similar to that of proportions of population of different religions in Delhi except for Jain religion where incidence of cancer is 6 times higher despite lesser number children in 0–6 year in this population as compared to other religions . Major difference is the diet lacking in onion and garlic . Other reason could be increased literacy levels in Jain community . This link between diet ,religion and cancer in Jain population needs to be studied in a larger muticenteric setting as it has implications for the whole world. No significant financial relationships to disclose.
Defining phenotypes of wheeze at preschool age: Comparison of episodic vs multitrigger wheeze
Authors: Elena Mutti, Simonetta Baraldo, Erica Bazzan, Graziella Turato, Deborah Snijders, Marco Damin, Riccardo Cazzuffi, Marco Poletti Poletti, Mariaenrica Tinè, Manuel Cosio, Angelo Barbato, Marina Saetta
Journal: European Respiratory Journal (2014)

Rationale  Wheeze at preschool age includes different disease entities. It has been proposed that episodic wheeze (only with viral infections) and multitrigger wheeze may represent distinct phenotypes.   Aim  To define clinical and pathological features typical of children with episodic or multitrigger wheeze at preschool age.   Methods  We studied 55 children undergoing bronchoscopy for clinical indications:11 with episodic wheeze (4;1-6 yrs), 24 with multitrigger wheeze (4;1-6) and 20 controls (4;2-6). Structural and inflammatory changes were assessed in bronchial biopsies by histochemistry and immunohistochemistry.   Results  Age at onset (1.2;0.5-4 vs 1;0-3.5yrs) and symptom duration (3;1-3.5 vs 2.5;1-6yrs) were similar in children with episodic and multitrigger wheeze. Prevalence of atopy (45%vs 40%) and number of infectious episodes (mean:1/month) were similar in the 2 groups. Children with episodic and those with multitrigger wheeze had similar airway pathology with higher numbers of mast cells (461;100-800 and 441;113-95/mm 2 ) and eosinophils (50;0-586 and 63;0-267/mm 2 ) compared to controls (143;8-650/mm 2 ,p=0.0005 and 9,0-200/mm 2 ,p=0.01). Epithelial loss and BM thickness were also increased in episodic and multitrigger wheezers and correlated with mast cell count (r=0.36,p   Conclusion  Children with episodic wheeze at preschool age are indistinguishable from those with multitrigger wheeze in pattern of symptom onset and duration, prevalence of atopy and airway pathology. This suggests that episodic and multitrigger wheezers represent the same disease with different attack predisposition.
Association of CMR-Measured LA Function With Heart Failure Development
Authors: Mohammadali Habibi, Harjit Chahal, Anders Opdahl, Ola Gjesdal, Thomas M. Helle-Valle, Susan R. Heckbert, Robyn McClelland, Colin Wu, Steven Shea, Gregory Hundley, David A. Bluemke, João A.C. Lima
Journal: JACC. Cardiovascular imaging (2014)
Risk and Responsibility
Authors: Harriet L. Hardy
Journal: New England Journal of Medicine (1975)

THE friendly confidence of the Society in inviting me before and after a surgical operation on my head to fill this time-honored and privileged post has given me pause indeed. What is fresh and important that can be distilled from forty years of a varied and satisfactory medical career that will prove stimulating or helpful to physicians?Drawing on 30 years of clinical study and care of patients with real or suspected job-related illness, I describe here some observations of risks taken daily by many workers and the responsibility of his doctor if a worker acquires disease that is occupational. . . .
Identification of neurodegenerative factors using translatome–regulatory network analysis
Authors: Lars Brichta, William Shin, Vernice Jackson-Lewis, Javier Blesa, Ee-Lynn Yap, Zachary Walker, Jack Zhang, Jean-Pierre Roussarie, Mariano J Alvarez, Andrea Califano, Serge Przedborski, Paul Greengard
Journal: Nature Neuroscience (2015)
Nuclear death: an unprecedented challenge to psychiatry and religion
Authors: J D Frank
Journal: American Journal of Psychiatry (1984)

The growing danger of a nuclear holocaust has intensified two aspects of the human predicament that concern both religion and psychiatry: the inevitability of death and the disastrous consequences of the characteristic termed "pride" by theologians and "narcissism" by psychiatrists. For the first time, humans have power to exterminate themselves and death threatens all ages equally. Pride of power causes leaders to exaggerate their ability to control nuclear weapons; moral pride leads to demonizing enemies. The author considers implications for psychiatrists and clergy, with special reference to preventing a nuclear holocaust.
Timeliness of End-of-Life Discussions for Blood Cancers
Authors: Oreofe O. Odejide, Angel M. Cronin, Nolan Condron, Craig C. Earle, Joanne Wolfe, Gregory A. Abel
Journal: JAMA Internal Medicine (2015)

dents and students can derive an ambivalent approach to value.Particularly in academic centers where resources seem limitless, attending physicians often suggest additional tests that expand exhaustive differential diagnoses.This builds on trainees' gnawing fear of missing something to establish thoroughness as an unrestrained virtue.The pressures of individualized quality metrics along with compressed inpatient evaluations to minimize length of stay may further reinforce this mindset and encourage defensive testing.These practices contradict and displace discussions of value.The research letter by Pierce et al 3 in this issue of JAMA Internal Medicine underscores the unrealized potential of rounds to teach high value.Pierce et al observed 168 patient encounters on internal medicine rounds and recorded how often an attending physician invoked the American College of Physicians' test-ordering appropriateness criteria. 3 Attending physicians only discussed appropriate test ordering during 35 (20.8%) of 168 patient encounters.They most often brought up whether a test affected care (23 encounters [13.7%]) and rarely discussed whether a test would cause harm (4 encounters [2.4%]).There is no standard on how often attending physicians should discuss value with trainees, and conversations that residents initiated about value were not captured in the study.However, the findings are in line with surveys of program directors, medical students, and residents who all noted missed opportunities for faculty to model these skills. 4 How might educators change the culture of rounds from rewarding meticulousness to celebrating moderation?Just as we challenge trainees to explain their diagnostic reasoning, so too should we probe them to justify their use of tests and resources.Attending physicians should model the confidence needed to enact a stepwise diagnostic workup.In addition to using evidencebased guidelines, we should reemphasize history and physical examination findings to refine and guide diagnostic workup.Finally, we should study such interventions to determine whether they affect practices as well as attitudes.
LP08 : Safety and efficacy of sofosbuvir-containing regimens in hepatitis C infected patients with reduced renal function: Real-world experience from HCV-target
Authors: V. Saxena, F.M. Koraishy, M. Sise, J.K. Lim, R.T. Chung, A. Liapakis, D.R. Nelson, M. Schmidt, M.W. Fried, N. Terrault
Journal: Journal of Hepatology (2015)
Review care of dying patients daily, says new NICE guideline
Authors: Nigel Hawkes
Journal: BMJ (2015)

People in their last few days of life are entitled to individualised care tailored to their needs, reviewed at least daily and openly discussed with them or their representatives, a new guideline says.

Rather than the “tick box, one size fits all” approach of the Liverpool care pathway (LCP), dying patients deserve “the best possible care based on each individual’s needs and wishes,” said Sam Ahmedzai, of the University of Sheffield, who chaired the panel that developed the guideline for the National Institute for Health and Care Excellence (NICE).1

It calls for fewer tests in the final days and for adequate hydration, by clinically assisted methods if necessary. The perception that hydration and some essential medicines were withheld …
Phase I trial of EC90 (keyhole-limpet hemocyanin fluorescein isothiocyanate conjugate) with GPI-0100 adjuvant followed by EC17 (Folate-Fluorescein Isothiocyanate Conjugate) in Patients (pts) with metastatic renal cell carcinoma (MRCC)
Authors: R. J. Amato, B. Fagbeyiro, R. Messmann, P. S. Low
Journal: Journal of Clinical Oncology (2005)

2590 Background: FolateImmune is a folate-receptor (FR)-targeted immunotherapy that induces an immune response against tumor cells by marking tumor cells with a folate-hapten conjugate targeted to over expressed FR in renal cell carcinoma. It is comprised of a vaccine containing EC90, an adjuvant (GP-0100), and a folate-hapten conjugate (Folate-FITC). Patients (pts) receive a series of subcutaneous (SQ) injections of EC90 vaccine to stimulate the production of antibodies to the fluorescein-hapten followed by SQ injections of EC17, which forms a molecular bridge between the tumor cell and the endogenous circulating anti-fluorescein IgG antibody. This may initiate an Fc-mediated immune response leading to antibody-dependent cellular cytotoxicity in phagocyotosis. Phase I objective is to optimize dose and schedule of EC90 vaccine/EC17 folate-targeted therapy. Methods: Eligibility: positive immunohistochemical confirmation of FRs, ECOG ≤1, life expectancy >12 wks, any prior therapy, normal organ/marrow function, measurable disease, no active CNS involvement. Results: Twenty-four pts enrolled: 18 male/6 females, median 59.6 (range 34–74) years. Pathologic classification: 19-clear cell/5-non clear cell. Grade 1–2 toxicity included: rash, puritus, nausea, dyspnea, and mild change in blood pressure with associated heart rate. One pt had persistent allergic skin reaction. Toxicities were tolerable. Antibody titers generated with EC90/GP-0100 vaccine were higher during a 4-wk vaccination schedule rather than a 3 or 5-wk schedule. Antibody titers declined during the EC17 administration, thus an EC90 booster is needed. Six pts remain stable for 6+ months. Conclusion: Six pts are being enrolled into cohort 5 with a planned EC90 boost during wk 4 of the 6-wks of EC17. Additional data will be updated and presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Endocyte Celgene, Chiron, Endocyte Celgene, Chiron, Endocyte
Financial Concerns About Participation in Clinical Trials Among Patients With Cancer
Authors: Yu-Ning Wong, Mark D. Schluchter, Terrance L. Albrecht, Al Bowen Benson, Joanne Buzaglo, Michael Collins, Anne Lederman Flamm, Linda Fleisher, Michael Katz, Tyler G. Kinzy, Tasnuva M. Liu, Sharon Manne, Seunghee Margevicius, Dawn M. Miller, Suzanne M. Miller, David Poole, Stephanie Raivitch, Nancy Roach, Eric Ross, Neal J. Meropol
Journal: Journal of Clinical Oncology (2015)

Purpose The decision to enroll in a clinical trial is complex given the uncertain risks and benefits of new approaches. Many patients also have financial concerns. We sought to characterize the association between financial concerns and the quality of decision making about clinical trials. Methods We conducted a secondary data analysis of a randomized trial of a Web-based educational tool (Preparatory Education About Clinical Trials) designed to improve the preparation of patients with cancer for making decisions about clinical trial enrollment. Patients completed a baseline questionnaire that included three questions related to financial concerns (five-point Likert scales): “How much of a burden on you is the cost of your medical care?,” “I'm afraid that my health insurance won't pay for a clinical trial,” and “I’m worried that I wouldn’t be able to afford the costs of treatment on a clinical trial.” Results were summed, with higher scores indicating greater concerns. We used multiple linear regressions to measure the association between concerns and self-reported measures of self-efficacy, preparation for decision making, distress, and decisional conflict in separate models, controlling for sociodemographic characteristics. Results One thousand two hundred eleven patients completed at least one financial concern question. Of these, 27% were 65 years or older, 58% were female, and 24% had a high school education or less. Greater financial concern was associated with lower self-efficacy and preparation for decision making, as well as with greater decisional conflict and distress, even after adjustment for age, race, sex, education, employment, and hospital location (P &lt; .001 for all models). Conclusion Financial concerns are associated with several psychological constructs that may negatively influence decision quality regarding clinical trials. Greater attention to patients’ financial needs and concerns may reduce distress and improve patient decision making.
National assessment of statin therapy for patients with acute myocardial infarction, 2001–11: insight from the China PEACE-Retrospective Acute Myocardial Infarction study
Authors: Lihua Zhang, Jing Li, Xi Li, Khurram Nasir, Haibo Zhang, Yongjian Wu, Shuang Hu, Qing Wang, Nicholas S Downing, Nihar R Desai, Frederick A Masoudi, John A Spertus, Harlan M Krumholz, Lixin Jiang
Journal: The Lancet (2015)