tbuckley/cabot-search huggingface dataset:
Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa
Authors: Ashraf Coovadia, Elaine J. Abrams, Renate Strehlau, Stephanie Shiau, Francoise Pinillos, Leigh Martens, Faeezah Patel, Gillian Hunt, Wei-Yann Tsai, Louise Kuhn
Journal: JAMA (2015)

Advantages of using efavirenz as part of treatment for children infected with human immunodeficiency virus (HIV) include once-daily dosing, simplification of co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for second-line treatment, and harmonization of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission.To evaluate whether nevirapine-exposed children achieving initial viral suppression with ritonavir-boosted lopinavir-based therapy can transition to efavirenz-based therapy without risk of viral failure.Randomized, open-label noninferiority trial conducted at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa, from June 2010 to December 2013, enrolling 300 HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission who were aged 3 years or older and had plasma HIV RNA of less than 50 copies/mL during ritonavir-boosted lopinavir-based therapy; 298 were randomized and 292 (98%) were followed up to 48 weeks after randomization.Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148).Risk difference between groups in (1) viral rebound (ie, ≥1 HIV RNA measurement of >50 copies/mL) and (2) viral failure (ie, confirmed HIV RNA >1000 copies/mL) with a noninferiority bound of -0.10. Immunologic and clinical responses were secondary end points.The Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n = 26) in the efavirenz group and 0.284 (n = 42) in the ritonavir-boosted lopinavir group. Probabilities of viral failure were 0.027 (n = 4) in the efavirenz group and 0.020 (n = 3) in the ritonavir-boosted lopinavir group. The risk difference for viral rebound was 0.107 (1-sided 95% CI, 0.028 to ∞) and for viral failure was -0.007 (1-sided 95% CI, -0.036 to ∞). We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end points. By 48 weeks, CD4 cell percentage was 2.88% (95% CI, 1.26%-4.49%) higher in the efavirenz group than in the ritonavir-boosted lopinavir group.Among HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission and with initial viral suppression with ritonavir-boosted lopinavir-based therapy, switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound or viral failure. This therapeutic approach may offer advantages in children such as these.clinicaltrials.gov Identifier: NCT01146873.
Protein and RNA Synthesis in Pituitary Tumors from F344 Rats Given Implants of Estrogen 2
Authors: Susana E. Kaplan, Alejandro F. de Nicola
Journal: JNCI Journal of the National Cancer Institute (1976)

The synthesis of total proteins, growth hormone, and prolactin and the incorporation of radioactive precursors into RNA was studied in pituitaries from normal F344 rats and rats given implants of 15 mg diethylstilbestrol (DES). Prolonged DES treatment (>50 days) induced pituitary tumors in male and female rats. The tumor tissue had a high rate of cell protein synthesis and an unusual capacity to synthesize a single-protein hormone (prolactin). After 17 days of DES treatment, the increase in prolactin synthesis in the hyperplastic pituitaries was not as marked as that in the tumors. At the time of tumor induction and high prolactin synthesis, incorporation of uridine or cytidine into RNA was not stimulated, and orotic acid incorporation in tumors from male rats was decreased. During early estrogen treatment (5 and 17 days), significantly less uridine was incorporated into RNA. These data suggested that the increment in protein and hormone synthesis promoted by DES may be related to a decrease in RNA turnover.
The usefulness of the simultaneous measurement of IOS and FeNO in the management of asthma
Authors: Soichiro Hozawa, Michikazu Terada, Maki Hozawa
Journal: European Respiratory Journal (2012)

[Background] The evaluation of airway lesions by impulse oscillometry (IOS) and the evaluation of fractional exhaled nitric oxide (FeNO) as the indicator of asthmatic airway inflammation attract attention. [Aim] To evaluate asthmatic airway lesions by simultaneous measurement of IOS and FeNO. [Methods]The subjects were the good controlled 65 patients with asthma (good controlled group), and 42 symptomatic treatment-free initial-visit patients with asthma(initial-visited group). These subjects were nonsmoker. For the patients in both groups, we measured IOS and FeNO at the same time. IOS measured by Masterscreen and FeNO measured by NIOX MINO. [Results]The level of FeNO was 73.1 ±7.5ppb in initial-visited group, and was 25.0±2.3ppb in good controlled group, and the initial-visited group significantly showed high level. In the good controlled group, the positive correlation was accepted between the following IOS parameters, such as the total airway resistance, the small airway component, the peripheral capacitive reactance and the reactance area, the resonant freguency and FeNO (p
Knowledge management systems for oral health in developing and developed countries
Authors: Anders Nattestad
Journal: Periodontology 2000 (2012)

Knowledge management systems utilize information technology to manage knowledge in organizations with the purpose of creating, supporting, storing and disseminating information. These systems have been around for decades, but have significantly changed over time in complexity and features with the evolution of information technology and the Internet. With the development of these new technologies, the concept of knowledge management has thrived and has had significant impact on the way in which knowledge is accumulated, stored and accessed. This article will describe the historical development of knowledge management systems in oral health, illustrate the technology using examples and explore the future use of these systems with emerging technologies such as Google Wave®. One example of how knowledge management systems may affect the quality of dental education is the DentEd project, where a collaborative website was developed to coordinate dental school visitations and collection of reports from working groups, leading to several important publications. MEDLINE is another example of an effective knowledge management system in health care, providing access to health care-related scientific literature, which is highly organized under the auspices of the United States National Library of Medicine. Another and very differently organized example of an effective knowledge management system is Wikipedia, which is a free, web-based, collaborative, multilingual encyclopedia project supported by a nonprofit foundation. The final example of an effective knowledge management system is all of the social media, including Facebook and Twitter. These tools have proven very powerful in organizing and collaborating. In conclusion, the development of new technologies and the Internet have changed the way in which information is developed and accessed. This development is still ongoing and only the future will reveal how this will continue to change.
Tobacco use and cessation for cancer survivors: An overview for clinicians
Authors: Maher Karam‐Hage, Paul M. Cinciripini, Ellen R. Gritz
Journal: CA A Cancer Journal for Clinicians (2014)

Answer questions and earn CME/CNE Approximately 30% of all cancer deaths in the United States are caused by tobacco use and smoking. Cancers of eighteen sites have been causally linked to smoking, the most common of which are the lung, head and neck, bladder, and esophagus. While quit rates and quit attempt rates are relatively high shortly after a cancer diagnosis, the recidivism rates are also high. Therefore, screening, treating, and preventing relapse to tobacco use is imperative among patients with and survivors of cancer. To date, research has consistently shown that a combination of pharmacologic and behavioral interventions is needed to achieve the highest smoking cessation rates, with a recent emphasis on individualized treatment as a most promising approach. Challenges in health care systems, including the lack of appropriate resources and provider training, have slowed the progress in addition to important clinical considerations relevant to the treatment of tobacco dependence (eg, a high degree of comorbidity with psychiatric disorders and other substance use disorders). However, continued tobacco use has been shown to limit the effectiveness of major cancer treatments and to increase the risk of complications and of developing secondary cancers. The authors recommend that oncology providers screen all patients for tobacco use and refer users to specialized treatment when available. Alternatively, oncology clinicians can provide basic advice on tobacco use cessation and pharmacotherapy and/or referral to outside resources (eg, quitlines). Herein, the authors summarize the current knowledge on tobacco use and its treatment, with a focus on the related available evidence for patients with and survivors of cancer. CA Cancer J Clin 2014;64:272–290. © 2014 American Cancer Society.
Night to night variability in sleep breathing pattern in people awaiting biventricular pacemaker for severe heart failure
Authors: Daniel Swamydass, Rachel Roberts, James Barry, Eiry Edmunds, Mark Andersen, Chris Warren, Keir Lewis
Journal: European Respiratory Journal (2014)

INTRODUCTION   The prevalence of sleep disordered breathing in people with left ventricular failure has been reported at 40-60% 1 .We wanted to look at night to night variations in sleep disordered breathing in a cohort of patients referred for biventricular pacemaker for heart failure (HF) according to national guidelines.   2    METHODS   Prospective, Observational study.  24 patients (19 males), with NYHA category 3-4, mean (SD) Left Ventricular Ejection Fraction =25 (7)%, QRS duration > 120 msec on ECG; all were deemed on optimal medical treatment for their HF by a Cardiologist. They had limited channel sleep studies (Apnea Link TM  ResMed, Abingdon, UK) for two consecutive nights, 7 days prior to elective implant biventricular pacemaker at a UK tertiary center. We compared the 2 sleep studies in all patients.   RESULTS   Night 1 versus Night 2, AHI correlation: Spearman9s rho =0.745, p=0.001  Cronbach9s Alpha=0.84 for repeatability.   CONCLUSION   There is no significant variation over two consecutive nights in sleep breathing patterns in those with severe HF who awaiting biventricular pacemaker. We recommend that one night of sleep study is reliable to diagnose sleep disordered breathing in patients with severe HF.   REFERENCES   1. Eur.Resp.J.2007.Jun:29(6)1201-5  2. www.nice.org.uk/TA120.
Crossreactive αβ T Cell Receptors Are the Predominant Targets of Thymocyte Negative Selection
Authors: Benjamin D. McDonald, Jeffrey J. Bunker, Steven A. Erickson, Masatsugu Oh-Hora, Albert Bendelac
Journal: Immunity (2015)

The precise impact of thymic positive and negative selection on the T cell receptor (TCR) repertoire remains controversial. Here, we used unbiased, high-throughput cloning and retroviral expression of individual pre-selection TCRs to provide a direct assessment of these processes at the clonal level in vivo. We found that 15% of random TCRs induced signaling and directed positive (7.5%) or negative (7.5%) selection, depending on strength of signal, whereas the remaining 85% failed to induce signaling or selection. Most negatively selected TCRs exhibited promiscuous crossreactivity toward multiple other major histocompatibility complex (MHC) haplotypes. In contrast, TCRs that were positively selected or non-selected were minimally crossreactive. Negative selection of crossreactive TCRs led to clonal deletion but also recycling into intestinal CD4(-)CD8β(-) intraepithelial lymphocytes (iIELs). Thus, broadly crossreactive TCRs arise at low frequency in the pre-selection repertoire but constitute the primary drivers of thymic negative selection and iIEL lineage differentiation.
NHS is “drowning in bureaucracy” and lacks good leaders, says scathing report
Authors: Ingrid Torjesen
Journal: BMJ (2015)

The NHS is “drowning in bureaucracy,” is beset with chronic problems that successive governments have ignored, and has a “chronic shortage of good leaders” to apply the “common sense” needed to sort it all out, says the long awaited report by the Conservative peer Stuart Rose into leadership in the NHS in England.1

“The level and pace of change in the NHS remains unsustainably high: this places significant, often competing demands on all levels of its leadership and management. The administrative, bureaucratic and regulatory burden is fast becoming insupportable,” says the report by the former executive chairman of the UK retail chain Marks & Spencer. “The whole organisation could and should be made more effective by the application of some common-sense tactical and strategic thinking.”

Many problems in the NHS “are chronic and have been unaddressed over an extended period and by different Governments,” and “more resource should be applied to the development of all management careers in the NHS,” the scathing report says.

Rose highlights three areas …
Gaining insights into pulmonary hypertension in respiratory diseases
Authors: Joan Albert Barberà, Isabel Blanco
Journal: European Respiratory Journal (2015)

Pulmonary hypertension (PH) associated with respiratory diseases, group 3 in the current classification [1], is one of the most frequent presentations of PH. Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are the two most common respiratory disorders associated with PH. In these conditions the presence of PH is associated with shorter survival [2, 3] and worse clinical course [4]. Yet, much is still unknown about group 3 PH regarding its prevalence in the whole disease spectrum, noninvasive markers that might facilitate its recognition and, most importantly, how to treat it. Pulmonary hypertension associated with respiratory disease is a difficult to manage condition with significant burden <http://ow.ly/S1COQ>
Transient left homonymous hemianopsia and encephalopathy following treatment of testicular carcinoma with cisplatinum, vinblastine, and bleomycin.
Authors: R J Cohen, R A Cuneo, M P Cruciger, A E Jackman
Journal: Journal of Clinical Oncology (1983)

A 36-year-old man being treated with cisplatinum, vinblastine, and bleomycin for testicular carcinoma developed a dense left homonymous hemianopsia, encephalopathy, and a partial nondominant parietal lobe syndrome. He subsequently had a resolution of all signs and symptoms, suggesting that these alarming events were a toxic but reversible side effect of the chemotherapy.
Marek's Disease Herpesvirus in Peripheral Nerve Lesions&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Tito Ubertini, B.W. Calnek
Journal: JNCI Journal of the National Cancer Institute (1970)

Journal Article Marek's Disease Herpesvirus in Peripheral Nerve Lesions Get access Tito Ubertini, Tito Ubertini Department of Avian Diseases, New York State Veterinary College, Ithaca, New York 14850 Search for other works by this author on: Oxford Academic PubMed Google Scholar B.W. Calnek B.W. Calnek Department of Avian Diseases, New York State Veterinary College, Ithaca, New York 14850 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 45, Issue 3, September 1970, Pages 507–514, https://doi.org/10.1093/jnci/45.3.507 Published: 01 September 1970 Article history Received: 25 February 1970 Accepted: 08 May 1970 Published: 01 September 1970
Does standardized medical treatment for parapneumonic empyema (PE) in children reduces the need for surgical intervention
Authors: Marijke Proesmans, Brenda Gijsen, Patricia van de Wijdeven, Herbert Decaluwé, Jan Verhaegen, Katrient Lagrou, Ellen Van Even, François Vermeulen, Kris De Boeck
Journal: European Respiratory Journal (2013)

Treatment of PE consist of intravenous antibiotics and in case of large effusions and persisting fever pleural chest drain (± intra-pleural fibrinolytics) or surgical intervention (VATS). We standardized the treatment for PE in our tertiary care center choosing for a first step non-surgical approach. The aim was to have prospective data on outcome and need for surgery on all children treated between 2006 and 2013 for PE. Definition of PE and treating algorithm have been published (Proesmans, M. and K. De Boeck. Eur J Pediatr 2009; 168: 639-45). Data on median length of stay, duration of fever, complications and need for additional surgical therapy. Additionally, data on the causative infectious agents were studied.  Results:132 children were treated for PE. Median duration of ‘in hospital fever’ was 5 days (IQR 3-8) and median hospital stay was 13 days (IQR 8-17). The duration of fever was inversely correlated with pleural pH (r= -0.28; p=0.04) and pleural glucose (r=-0.34; p=0.004).  The need for surgery dropped progressively from almost 40% in 2007 to 0% in 2010 again increasing to 40% in 2012. Overall, 20% of children needed surgical intervention. Based on pleural PCR data, 85% of PE were caused by  S pneumonia  (40% serotype 1). Pneumococcal antigen detection had a positive predictive value of 98% with a negative predictive value of 56%.  Conclusion: Since 2006 all children with PE are strictly treated according to a standardized approach and outcome is registered prospectively. After an initial drop in the need for surgical intervention, the need for surgical rescue interventions increased again. This may be due to change in serotypes or disease severity.
High resolution SNP array analysis of primary ovarian tumors reveals numerous microdeletions and amplifications.
Authors: Ian Campbell, Sharoni Jacobs, Ella Thompson, Kylie Gorringe
Journal: Clinical Cancer Research (2007)

A63   Genetic changes in sporadic ovarian cancer are poorly characterized. We have evaluated 31 primary ovarian cancers for loss of heterozygosity (LOH) and copy number alterations using the Affymetrix GeneChip® Mapping 500K Arrays. We analyzed DNA extracted from fresh frozen tumor and matching normal lymphocytes from 31 women with primary epithelial ovarian cancer, including three different histological subtypes - mucinous, endometrioid and serous. Analysis of the number of copy number breakpoints and the distribution of the small regions of copy number change indicate high levels of structural chromosomal genetic instability in ovarian cancer. There were differences in the number of chromosome breakpoints with tumor subtype, grade and stage. In addition to identifying the expected large-scale genomic copy number changes, the 500K array also revealed numerous smaller regions (
70-kDa heat shock protein coated magnetic nanocarriers as a nanovaccine for induction of anti-tumor immune response in experimental glioma
Authors: Maxim A. Shevtsov, Boris P. Nikolaev, Liudmila Y. Yakovleva, Marina A. Parr, Yaroslav Y. Marchenko, Igor Eliseev, Anna Yudenko, Anatolii V. Dobrodumov, Olga Zlobina, Alexander Zhakhov, Alexander M. Ischenko, Emil Pitkin, Gabriele Multhoff
Journal: Journal of Controlled Release (2015)
Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding
Authors: Niloufar Kavian, Wioleta Marut, Amélie Servettaz, Carole Nicco, Christiane Chéreau, Hervé Lemaréchal, Philippe Guilpain, Giovanna Chimini, Franck Galland, Bernard Weill, Philippe Naquet, Frédéric Batteux
Journal: Arthritis & Rheumatology (2015)

Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc. First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage. In vitro, pantethine inhibited MP shedding from tumor necrosis factor-stimulated ECs and abrogated MP-induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1. Pantethine is a well-tolerated molecule that represents a potential treatment of human SSc.
Peripheral-blood stem-cell transplantation versus autologous bone marrow transplantation in Hodgkin's and non-Hodgkin's lymphomas: a new matched-pair analysis of the European Group for Blood and Marrow Transplantation Registry Data. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
Authors: I Majolino, R Pearce, G Taghipour, A H Goldstone
Journal: Journal of Clinical Oncology (1997)

PURPOSE To address the question of short-term and long-term advantages of peripheral-blood stem-cell transplantation (PBSCT) over autologous bone marrow transplantation (ABMT), we have reviewed the data of 3,214 patients with lymphoma, 2,859 undergoing ABMT, and 355 undergoing PBSCT. PATIENTS AND METHODS Analysis of prognostic factors for progression-free survival (PFS) was conducted separately for non-Hodgkin's lymphoma (NHL) (N = 1,915) and Hodgkin's disease (HD) (N = 1,299). In multivariate analysis, the relevant factors were status at transplant for NHL and sex, size of largest mass at transplant, status at transplant, and conditioning regimen for HD. The pair analysis was carried out by matching NHL and HD patients separately by their prognostic factors. Additionally, NHL patients were matched for histology, whereas both HD and NHL patients were matched for date of transplant. With this method, 454 patients were matched in the NHL group and 256 were matched in the HD group. RESULTS The overall survival (OS) and PFS unexpectedy were better for ABMT versus PBSCT patients in the HD group (OS, 65.3% at 4 years for ABMT v 52.7% for PBSCT; P = .0198). There was no difference in OS or PFS in the NHL group (OS, 56.6% at 4 years for ABMT v 52.7% for PBSCT; P = .4148). The overall relapse or progression rate at 4 years for NHL was 42% after ABMT and 49.2% after PBSCT (P = .1220); for HD, it was 40% and 58.6%, respectively (P = .0164). Transplant-related mortality was lower, but not significantly, with PBSCT: 7.0% for ABMT versus 3.5% for PBSCT in NHL (P = .1356) and 7% for ABMT versus 4.7% for PBSCT in HD (P = .6056). Hematologic recovery occurred faster significantly with PBSCT irrespective of disease. CONCLUSION This study confirms the advantage of PBSCT in terms of hematopoietic reconstitution, but it fails to show any superiority in the long term. Poorer results for both progression free and overall survival observed in HD patients who are receiving PBSCT are unexplained and should be confirmed with randomized studies.
Social Determinants of Risk and Outcomes for Cardiovascular Disease
Authors: Edward P. Havranek, Mahasin S. Mujahid, Donald A. Barr, Irene V. Blair, Meryl S. Cohen, Salvador Cruz-Flores, George Davey-Smith, Cheryl R. Dennison-Himmelfarb, Michael S. Lauer, Debra W. Lockwood, Milagros Rosal, Clyde W. Yancy
Journal: Circulation (2015)