tbuckley/cabot-search huggingface dataset:
Abstract 3750: The novel Akt inhibitor MK-2206, is cytotoxic in T-cell acute lymphoblastic leukemia: Therapeutic implications
Authors: Carolina Simioni, Alice Cani, Daniela Bressanin, Camilla Evangelisti, Francesca Chiarini, Silvano Capitani, Luca M. Neri, Alberto M. Martelli
Journal: Cancer Research (2012)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive neoplastic disorder arising within the thymus from the clonal proliferation of T-cell precursors. T-ALL accounts for 15% of ALL cases in children and 25% in adults. Although the prognosis of T-ALL has improved, due to the use of intensive polychemotherapy schemes, the outcome of relapsed and chemoresistant T-ALL is still poor, especially in adults, with a 35-40% survival at 5 years. Therefore, efforts are being made to develop targeted therapies against deregulated signaling cascades that sustain T-ALL cell proliferation, survival, and drug-resistance. A signaling pathway that is frequently upregulated in T-ALL, is the PI3K/Akt/mTOR network. To explore whether or not Akt could represent a potential target for therapeutic intervention in T-ALL, we evaluated the effects of the novel allosteric Akt inhibitor, MK-2206, on a panel of human T-ALL cell lines (MOLT-4, CEM, drug-resistant CEM) and primary cells from T-ALL patients, characterized by pathway upregulation. MK-2206 decreased T-ALL cell line viability as documented by MTT assays. IC50 for MK-2206 ranged from 1.0 to 4.8 μM at 48 hours. The drug was effective against drug-resistant CEM cells, overexpressing 170-kDa P-glycoprotein. MK-2206 blocked leukemic cells in the G1 phase of the cell cycle and induced caspase-dependent apoptotic cell death, as documented by Annexin V/propidium iodide staining and western blot analysis. In CEM cells, MK-2206 induced autophagy, as demonstrated by an increase in the 14-kDa form of LC3A/B. Western blotting documented a concentration-dependent dephosphorylation of Akt and its downstream targets, GSK-3β and FOXO3A, in response to MK-2206. mTORC1 downstream targets were also efficiently dephosphorylated by MK-2206, including p70S6K and 4E-BP1. MK-2206 decreased mTORC2 activity, as indicated by the downregulation of Ser 2481 p-mTOR levels, a readout for mTORC2 activity In MOLT-4 and CEM cells, MK-2206 strongly synergized (combination index: 0.1-0.33) with doxorubicin. Moreover, MK-2206 dephosphorylated Akt and induced apoptosis in a T-ALL patient cell subset (CD34+/CD4−/CD7−) which is enriched in leukemia initiating cells. Our findings indicate that Akt inhibition, either alone or in combination with chemotherapeutic drugs, represents a potential therapeutic target in T-ALL cells that require upregulation of the PI3K/Akt/mTOR signaling pathway for their proliferation and survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3750. doi:1538-7445.AM2012-3750
Abstract 377: Multifunctional magnetic nanoparticles for theranostic applications
Authors: Murali M. Yallapu, Shadi F. Othman, Evan T. Curtis, Brij K. Gupta, Meena Jaggi, Subhash C. Chauhan
Journal: Cancer Research (2011)

Abstract Nanoparticle technology address efficacy of cancer chemotherapy and diagnosis which can be potentially used for image guided drug delivery. Herein, we have developed a multi-layer approach for the synthesis of water-dispersible iron oxide theranostic nanoparticles for drug delivery (therapy) and magnetic resonance imaging (MRI) (diagnostic) applications. For this novel approach, iron oxide core nanoparticles were prepared by precipitation of iron salts in the presence of ammonia and coated with beta-cyclodextrin and pluronic polymer (F127). This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in beta-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and beta-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug loaded formulation of F127250 exhibited many folds of imaging contrast properties. Curcumin, a cancer preventive and anti-cancer drug, loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects of this formulation were verified by examining ultra structural changes and molecular effects in cancer cells. Interestingly, F127250-CUR formulation also exhibited good haemo-compatibility. In conclusion, our data suggest that the F127250-CUR formulation can be effectively used for the delivery of anti-cancer drug drugs and cancer imaging and its potential clinical application. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 377. doi:10.1158/1538-7445.AM2011-377
Estimates of Infectious Disease Risk Factors in US Blood Donors
Authors: Alan E. Williams
Journal: JAMA (1997)

Individuals who do not respond accurately to questions about infectious disease risk factors at the time of blood donation represent a potential threat to the safety of the blood supply. This study was designed to estimate the prevalence of undetected behavioral and other risks in current blood donors.Anonymous mail surveys to collect demographic, medical, and behavioral information were administered to individuals who had donated blood within the previous 2 months. Sampling weights were used in the analysis to adjust for differential sampling and response rates among demographic groups to provide prevalence estimates for the donor population.Five geographically and demographically diverse US blood centers.A stratified probability sample of 50,162 allogeneic blood donors.Estimated prevalence rates for risk behaviors that would have been a basis for deferral if reported at the time of the donor screening interview (deferrable risk).Completed questionnaires were received for 34,726 donors (69.2% of the sample). A total of 186 per 10,000 respondents (1.9%) reported a deferrable risk that was present at the time of their past donation, while 39 per 10,000 (0.4%) reported this behavior within the 3 months prior to donation. Rates (with 95% confidence intervals [CIs]) of deferrable risk behaviors were 1.4 (95% CI, 1.2-1.6) times higher for men than women, 1.6 (95% CI, 1.3-2.0) times higher for first-time vs repeat donors, 2.7 (95% CI, 2.0-3.6) times higher for donors with reactive screening tests, and 7.6 (95% CI, 3.6-15.8) times higher for donors who used the confidential unit exclusion option.Despite the high degree of transfusion safety in the United States today, a measurable percentage of active blood donors when assessed by anonymous survey report risks for human immunodeficiency virus and other infections not reported at the time of screening, suggesting the need for further refinements in the blood donor qualification process.
Scientists Probe Strategies to Curb Hospital-Acquired Infections
Authors: Bridget M. Kuehn
Journal: JAMA (2012)

A 6-FOOT–TALL ROLLING ROBOT that emits UV light may help reduce colonization of hospital surfaces by such problematic pathogens as Clostridium difficile, Acinetobacter, and vancomycin-resistant enterococci (VRE), according to research findings presented at IDWeek 2012, a scientific meeting held by the Infectious Diseases Society of America, the Society for Healthcare Epidemiology, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. The robot study was one of many reportspresentedfromresearchthatisprobing theeffectivenessofvarious strategies tocurbhospital-acquired infections.Anotherpresentation, fromalargerandomized trial, suggested that regularly bathing all patients in intensive care units (ICUs)withtheantisepticchlorhexidine may prevent the spread of methicillinresistantStaphylococcusaureus (MRSA).
TCT-688 Treatment of bifurcation lesions with a Drug Eluting Stent with biodegradable polymer
Authors: Fazilatum Nesa Malik, Antonio Serra, Nick West, Werner Scholtz, Farzin Fath-Ordoubadhi, Teguh Santoso, Peep Laanmets, Werner Jung, Fraser Witherow, Stefan Hoffmann, Mohsen Mohandes, Gian Battista Danzi
Journal: Journal of the American College of Cardiology (2012)
Student Vaccination Requirements of U.S. Health Professional Schools: A Survey
Authors: Megan C. Lindley, Suchita A. Lorick, Jovonni R. Spinner, Andrea R. Krull, Gina T. Mootrey, Faruque Ahmed, Rosa Myers, Geraldine P. Bednash, Tyler C. Cymet, Rika Maeshiro, C. Fay Raines, Stephen C. Shannon, Henry M. Sondheimer, Raymond A. Strikas
Journal: Annals of Internal Medicine (2011)

Unvaccinated health care personnel are at increased risk for transmitting vaccine-preventable diseases to their patients. The Advisory Committee on Immunization Practices (ACIP) recommends that health care personnel, including students, receive measles, mumps, rubella, hepatitis B, varicella, influenza, and pertussis vaccines. Prematriculation vaccination requirements of health professional schools represent an early opportunity to ensure that health care personnel receive recommended vaccines.To examine prematriculation vaccination requirements and related policies at selected health professional schools in the United States and compare requirements with current ACIP recommendations.Cross-sectional study using an Internet-based survey.Medical and baccalaureate nursing schools in the United States and its territories.Deans of accredited medical schools granting MD (n = 130) and DO (n = 26) degrees and of baccalaureate nursing programs (n = 603).Proportion of MD-granting and DO-granting schools and baccalaureate nursing programs that require that entering students receive vaccines recommended by the ACIP for health care personnel.563 schools (75%) responded. More than 90% of all school types required measles, mumps, rubella, and hepatitis B vaccines for entering students; varicella vaccination also was commonly required. Tetanus, diphtheria, and acellular pertussis vaccination was required by 66%, 70%, and 75% of nursing, MD-granting, and DO-granting schools, respectively. Nursing and DO-granting schools (31% and 45%, respectively) were less likely than MD-granting schools (78%) to offer students influenza vaccines free of charge.Estimates were conservative, because schools that reported that they did not require proof of immunity for a given vaccine were considered not to require that vaccine. Estimates also were restricted to schools that train physicians and nurses.The majority of schools now require most ACIP-recommended vaccines for students. Medical and nursing schools should adopt policies on student vaccination and serologic testing that conform to ACIP recommendations and should encourage annual influenza vaccination by offering influenza vaccination to students at no cost.None.
New edicts for letters to the editor
Authors: S. Davies
Journal: BMJ (2003)

Your letters are very important to us. They are crucial to the success of the BMJ , and we appreciate their enthusiasm, different perspectives, diversity, and ability to stimulate debate, not to mention their wit and thoughtfulness. In the printed version of the BMJ , letters are edited only lightly for clarity and readability so that the author's voice is still audible and louder than in any other part of the journal. The letters pages are the readers' forum.

We select letters for the paper journal from the unedited rapid responses posted daily on bmj.com.1 We consider the electronic journal to be the BMJ , and we want the letters columns in the paper journal to reflect the liveliness of conversations on the web and be a bridge for the two communities of readers to access the two forms of the journal. In essence, we are saying: “Here are what we thought were the most interesting responses, but why not visit bmj.com yourself to see the full debate and how it …
An ecumenical practice?
Authors: G. Houghton
Journal: BMJ (2003)

The NHS is regularly accused of the sins of today such as institutional racism. I would like to report that in February 2002, our suburban general practice consisted of four partners, a new GP registrar, and a preregistration house officer. We all appreciated each other's worth and worked well together, even though we comprised a Roman Catholic, a Protestant, a Hindu, an agnostic, a Muslim, and a Jew. Could this be a multifaith first?
A cystic fibrosis transmembrane conductance regulator splice variant with partial penetrance associated with variable cystic fibrosis presentations.
Authors: E Kerem, N Rave-Harel, A Augarten, I Madgar, M Nissim-Rafinia, Y Yahav, R Goshen, L Bentur, J Rivlin, M Aviram, A Genem, O Chiba-Falek, M R Kraemer, A Simon, D Branski, B Kerem
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Some patients express various features of cystic fibrosis (CF) even though essential characteristics of the disease might be absent. Such patients may suffer from respiratory disease without pancreatic insufficiency and normal sweat chloride levels. Others may present as male infertility because of congenital bilateral aplasia of the vas deferens (CBAVD) with no other signs of CF. The 5T allele, a DNA variant in a noncoding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that reduces the level of the normal CFTR transcripts, was found in increased frequency among male patients with CBAVD. The purpose of this study was to investigate the possibility that the 5T allele is associated with dysfunction of organs other than the male reproductive system, leading to CF or atypical CF. Analysis of the 5T allele was performed on 148 subjects (29 with CF, 61 with atypical CF, and 58 with CBAVD) carrying 232 chromosomes with unidentified CFTR mutations, and on 142 non-CF chromosomes from healthy subjects of Ashkenazi origin. The frequency of the 5T allele among chromosomes from patients of Jewish Ashkenazi origin with CF and atypical CF (six of 33; 18%) was significantly higher than the frequency in the normal Ashkenazi population (eight of 142; 6%; p = 0.03). Analysis of the clinical presentation of the five patients with CF and the 12 patients with atypical CF carrying the 5T allele indicated that most patients suffered from respiratory disease presenting as asthma like symptoms, nasal polyposis, chronic sinusitis, chronic bronchitis, or bronchiectasis. Six patients had pancreatic insufficiency, two with meconium ileus. Sweat Cl- levels ranged from normal to elevated. Of the six male patients with respiratory disease who were old enough to be evaluated for fertility status, five were fertile and one had pancreatic insufficiency. Among male patients with CBAVD, 41% suffered from respiratory symptoms. Thus, the 5T allele is a variant with partial penetrance causing disease with an extreme variability of clinical presentation: from normal healthy fertile subjects or male patients with CBAVD to those with atypical or typical clinical phenotype of CF.
Gene-Expression Signatures in Breast Cancer
Authors: Christos Sotiriou, Lajos Pusztai
Journal: New England Journal of Medicine (2009)

This review discusses the results of DNA microarray signatures in breast cancer. These signatures have been useful in the classification of breast cancers, and they have an association with clinical outcomes. Surprisingly, there is little overlap in the types of genes among several useful microarray signatures. The true value of these signatures will become apparent only when prospective trials, now in progress, have been completed.
Evolutionary explanations need to account for cultural variation
Authors: Steven J. Heine
Journal: Behavioral and Brain Sciences (2011)

Abstract Cultural variability in self-enhancement is far more pronounced than the authors suggest; the sum of the evidence does not show that East Asians self-enhance in different domains from Westerners. Incorporating this cultural variation suggests a different way of understanding the adaptiveness of self-enhancement: It is adaptive in contexts where positive self-feelings and confidence are valued over relationship harmony, but is maladaptive in contexts where relationship harmony is prioritized.
NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity
Authors: Florence Armstrong, Philippe Brunet de la Grange, Bastien Gerby, Marie-Christine Rouyez, Julien Calvo, Michaéla Fontenay, Nicolas Boissel, Hervé Dombret, André Baruchel, Judith Landman-Parker, Paul-Henri Roméo, Paola Ballerini, Françoise Pflumio
Journal: Blood (2008)
155 IMPACT OF THE USE OF ALBUMIN FOR COMPLICATIONS OF CIRRHOSIS ON THE GLOBAL ALBUMIN CONSUMPTION AND PHARMACEUTICAL COSTS IN AN ACADEMIC HOSPITAL
Authors: F. Mirici-Cappa, P. Caraceni, E. Gelonesi, V. Bevilacqua, B. Benazzi, M. Domenicali, F. Trevisani, C. Puggioli, M. Bernardi
Journal: Journal of Hepatology (2010)
Roger Doidge Willcock
Authors: Jennifer Willcock
Journal: BMJ (2004)

Former general practitioner Telford (b 1923; q Guy's Hospital, London, 1947), died from ischaemic heart disease and diabetes on 26 March 2004.

After house officer posts he did 18 months' national service in the Royal Navy at Portsmouth and Londonderry. From 1950 he spent the rest of his professional life in general practice, first in Stoke-on-Trent, then Shrewsbury, and finally in Telford. He retired in 1986 and enjoyed nearly 18 years of retirement. He leaves a wife, Jennifer; three sons; and six grandsons.
Gall bladder lithotripsy.
Authors: M. C. Bateson
Journal: BMJ (1989)

this does not mean that I avoid the peer review process, as was implied.Dr Lawrence and col- leagues also choose to disregard the evidence I put forward in favour of transcutaneous electrical nerve stimulation but raise the controversial (and again not physical) point of drug treatment.In summary, they are mistaken to state that there is no evidence for benefit from physical treatments.In my view the BMJ7 rightly and courageously took up the much neglected subject of physical therapy.
S69 Serum osteoprotegerin predicts mortality in a prospective study on incident cases of pulmonary arterial hypertension
Authors: R. Condliffe, J. Pickworth, K. Hopkinson, A. Hameed, S. Walker, C. Elliot, S. Francis, C. Newman, D. Crossman, A. Morton, D. Kiely, A. Lawrie
Journal: Thorax (2011)

<h3>Background and Objectives</h3> Despite improvements in the overall management of Pulmonary Arterial Hypertension (PAH) the disorder still causes significant morbidity and mortality. Current treatments fail to reverse the disease, and clinical assessment does not always differentiate between, or reflect, the local pathogenesis within the heart or pulmonary circulation. Current proposed biomarkers, for example, brain natriuretic peptide (BNP and NT-proBNP), largely reflects myocardial rather than pulmonary vascular remodelling. Subsequently, there has been increasing interest in identifying a biomarker for PAH that can track with lung pathology, and treatment. Through our desire to understand disease pathogenesis, our studies in vitro and in animal models have identified osteoprotegerin (OPG) as a candidate biomarker. We have previously reported that OPG was elevated in a prevalent cohort of patients with IPAH. The aim of this study was to verify the utility of OPG as a biomarker for PAH in a second cohort of incident cases and assess the effect of treatment at follow-up visits. <h3>Methods</h3> Serum samples were obtained from 35 patients with IPAH, 26 patients with CTD-PAH and 65 age-matched controls. Serum OPG concentrations were measured by ELISA, correlations with pulmonary haemodynamics, routine clinical biochemistry and prognostic significance were then assessed. <h3>Results</h3> OPG concentrations were significantly elevated in IPAH (mean 4485 pg/ml) and CTD-PAH (3824 pg/ml) compared to controls (1749 pg/ml). Concentrations of OPG correlated positively with pulmonary vascular resistance (PVR) and WHO functional class and negatively with the incremental shuttle walk test (ISWT). An OPG concentration above 4744 pg/ml predicted poorer survival. OPG was significantly lower in patients at follow-up after the commencement of targeted PAH therapies. <h3>Conclusion</h3> PAH is characterised by elevated serum OPG and this correlates with functional class and PVR. Perhaps most importantly high serum levels of OPG predict a poor outcome. Further longitudinal work is required, and is currently underway to further validate these findings.
Storage (Irritative) and Voiding (Obstructive) Symptoms as Predictors of Benign Prostatic Hyperplasia Progression and Related Outcomes
Authors: Claus G Roehrborn, John D McConnell, Brian Saltzman, Donald Bergner, Todd Gray, Perinchery Narayan, Thomas J Cook, Amy O Johnson-Levonas, Wilson A Quezada, Joanne Waldstreicher
Journal: European Urology (2002)
On Awakening Paralyzed During Surgery
Authors: David R. Jobes
Journal: JAMA (1976)

To the Editor.—  As an anesthesiologist primarily involved in anesthesia for cardiac surgey, I would like to comment on the article by Dr Blacher. Five of the six cases reported were of patients who had had cardiac surgery. Patients with significant cardiac disease tolerate anesthesia poorly, and often we are faced with the necessity of using very light levels because of their marked effect on the cardiovascular system.1In all five patients, anesthetic management consisted of a narcotic supplemented by nitrous oxide, muscle relaxant, and tranquilizer. This technique has become popular because these drugs have less pronounced cardiovascular effects than techniques using potent inhalation agents. In either technique, there may be only a slight depression of the central nervous system during some phases of intraoperative management, and this results in a very real potential for awareness.2In recognition of this problem, the following steps may be taken to