tbuckley/cabot-search huggingface dataset:
Phase 2 Trial Of Single Agent MLN9708 In Patients With Relapsed Multiple Myeloma Not Refractory To Bortezomib
Authors: Vivek Roy, Craig Reeder, Betsy R. LaPlant, Martha Q Lacy, Morie A Gertz, Macp, Kristina Laumann, Melanie Ann Thompson, Thomas E Witzig, Francis K Buadi, Candido E. Rivera, Joseph R. Mikhael, Peter Leif Bergsagel, Lisa Hwa, Cnp, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2013)
Naltrexone-induced dysphoria in former opioid addicts
Authors: T J Crowley, J E Wagner, G Zerbe, M Macdonald
Journal: American Journal of Psychiatry (1985)

Naltrexone treatment, used to prevent relapse among former opioid addicts, is reported to have an extraordinary rate of noncompliance. Since activation of opioid receptors produces a sense of well-being, naltrexone's blockade of these receptors might produce dysphoria, which could contribute to noncompliance among addicts under treatment. To test this hypothesis, the authors administered naltrexone to four men who had been free of opioids for 9 to 44 months using a 6-week, placebo-controlled crossover design. One subject dropped out with abstinence-like symptoms, and two others reported mild but significantly greater dysphoria during naltrexone administration. The results suggest that naltrexone may induce mild dysphoria long after addicts stop using opioids.
Heterogeneity in Tumors and Resistance to EGFR TKI Therapy—Response
Authors: Takeshi Shimamura
Journal: Cancer Research (2016)

We read with great interest the letter from Suda and colleagues ([1][1]) regarding our recent article titled “Intratumoral Heterogeneity in EGFR-Mutant NSCLC Results in Divergent Resistance Mechanisms in Response to EGFR Tyrosine Kinase Inhibition” ([2][2]). We believe that most of their
Relationship between the proportion of natural killer cells in peripheral blood lymphocytes and risk factors in cervical cancer
Authors: S. Jang, S. Jang, E. Nam, D. Lee, J. Hong, S. Kim, S. Kim, J. Kim, Y. Kim, J. Kim
Journal: Journal of Clinical Oncology (2008)

16546 Background: Natural Killer (NK) cells lyse target cells and provide source of immunoregulatory cytokines. The aim of this study was to investigate relationship between preoperative proportion of NK cells in peripheral blood lymphocytes and risk factors in cervical cancer patients who underwent radical hysterectomy. Methods: The pathologic reports of 57 cervical cancer patients who underwent radical hysterectomy from September 2004 to December 2007 were reviewed. Preoperative proportion of NK cells in peripheral blood were measured by flowcytometry method. We reviewed medical records for comparison of the risk factors which were supposed to be related to cervix cancer including age, clinical stage, squamous cell carcinoma antigen (SCC), cell type, tumor size, invasion depth, lymphovascular invasion and nodal metastasis. Group A (n=40) was defined as those with NK cells proportion < 15% and group B (n=17) with NK cells proportion ≥ 15%. Relationship between proportion of NK cell and prognostic factors of cervical cancer were analyzed. Results: NK cell proportion of Stage II cervix cancer patients was higher than that of stage I (p = 0.038). When comparing group A with group B, risk factors including clinical stage (p = 0.010), invasion depth (p = 0.034) and SCC level (p = 0.047) were significant decrease in group A. Other factors, such as nodal metastasis, tumor size, cell type and lymphovascular invasion, were not significant related between group A and group B. Conclusion: Risk factors of cervix cancer, such as clinical stage, invasion depth and SCC Ag level, were positively related to NK cells proportion. Increase of Natural Killer cell proportion in peripheral blood lymphocytes may be related to poor prognosis of cervix cancer. No significant financial relationships to disclose.
Anaesthetics training in the United States
Authors: P R Hambly
Journal: BMJ (1995)

patients' satisfaction but, more importantly, outcome.Indeed, anaesthetists and surgeons may also attach greater importance to pain relief and, in particular, regional anaesthesia if the promising results of recent research are borne out by larger controlled studies.'If a combination of new surgical techniques, high quality analgesia, and aggressive rehabilitation can reduce the mean length of stay after major surgery by half, then both providers and purchasers should be interested in the role of regional analgesia in the outcome of surgery.This will require a great change in clinicians' attitudes to postoperative care and an injection of new moneys in the short term.Whether either of these developments occurs remains to be seen.
OP25INTRAVENOUS DELIVERY OF ONCOLYTIC REOLYSIN<sup>®</sup>TO PRIMARY AND SECONDARY BRAIN TUMOURS
Authors: A. Jebar, E. West, K. Scott, G. Nuovo, M. Fuller, S. Thomson, R. Corns, R. Mathew, G. SivaKumar, J. Cockle, P. Van Hille, F. Errington, E. Appleton, G. Migneco, D. Taggart, M. Coffey, A. Rose, S. Griffin, Ralph C. Anth
Journal: Neuro-Oncology (2015)

INTRODUCTION: Oncolytic viruses preferentially replicate in cancer cells and kill them through direct cytotoxicity and/or immune mediated cell destruction. REOLYSIN® is a proprietary isolate of reovirus type 3 Dearing. In previous trials using intra-lesional administration REOLYSIN® was well tolerated, and there were early signs of efficacy. However, intravenous delivery is a less invasive means of administration that would permit more frequent dosing. This trial aims to identify whether REOLYSIN® can infect primary and secondary brain tumours following intravenous administration. METHOD: This is an open-label, non-randomised study of intravenous REOLYSIN® administered to patients prior to planned surgery for recurrent high-grade glioma or metastatic brain tumours. 12 patients will be treated with a single infusion of 1x1010 TCID50 of REOLYSIN®. The primary objective is the presence of REOLYSIN® in the resected tumours as assessed by immunohistochemistry, RNA in-situ hybridization and retrieval of infectious virions. RESULTS: 9 patients have completed the study to date, including 4 glioblastoma multiforme, 2 grade III glioma and 2 brain metastases cases. 3 of 4 resected GBM patient tumours and both Gd III gliomas contained REOLYSIN® RNA and/or protein. There was evidence for REOLYSIN® productive infection in 8 of the 9 treated tumours. Grade 3-4 adverse reactions were neutropaenia (1 patient) and lymphopaenia (3 patients). CONCLUSION: We have shown for the first time that an oncolytic virus, REOLYSIN®, infects and replicates in primary and secondary brain tumours following intravenous administration. This trial will pave the way for phase I/II trials and combination studies using REOLYSIN® in brain tumour patients.
ICOS Promotes the Function of CD4+ Effector T Cells during Anti-OX40–Mediated Tumor Rejection
Authors: Todd C. Metzger, Hua Long, Shobha Potluri, Thomas Pertel, Samantha L. Bailey-Bucktrout, John C. Lin, Tihui Fu, Padmanee Sharma, James P. Allison, Reid M.R. Feldman
Journal: Cancer Research (2016)

Abstract ICOS is a T-cell coregulatory receptor that provides a costimulatory signal to T cells during antigen-mediated activation. Antitumor immunity can be improved by ICOS-targeting therapies, but their mechanism of action remains unclear. Here, we define the role of ICOS signaling in antitumor immunity using a blocking, nondepleting antibody against ICOS ligand (ICOS-L). ICOS signaling provided critical support for the effector function of CD4+ Foxp3− T cells during anti-OX40–driven tumor immune responses. By itself, ICOS-L blockade reduced accumulation of intratumoral T regulatory cells (Treg), but it was insufficient to substantially inhibit tumor growth. Furthermore, it did not impede antitumor responses mediated by anti-4-1BB–driven CD8+ T cells. We found that anti-OX40 efficacy, which is based on Treg depletion and to a large degree on CD4+ effector T cell (Teff) responses, was impaired with ICOS-L blockade. In contrast, the provision of additional ICOS signaling through direct ICOS-L expression by tumor cells enhanced tumor rejection and survival when administered along with anti-OX40 therapy. Taken together, our results showed that ICOS signaling during antitumor responses acts on both Teff and Treg cells, which have opposing roles in promoting immune activation. Thus, effective therapies targeting the ICOS pathway should seek to promote ICOS signaling specifically in effector CD4+ T cells by combining ICOS agonism and Treg depletion. Cancer Res; 76(13); 3684–9. ©2016 AACR.
Stat3 Controls Tubulointerstitial Communication during CKD
Authors: Frank Bienaimé, Mordi Muorah, Lucie Yammine, Martine Burtin, Clément Nguyen, Willian Baron, Serge Garbay, Amandine Viau, Mélanie Broueilh, Thomas Blanc, Dorien Peters, Valeria Poli, Dany Anglicheau, Gérard Friedlander, Marco Pontoglio, Morgan Gallazzini, Fabiola Terzi
Journal: Journal of the American Society of Nephrology (2016)

In CKD, tubular cells may be involved in the induction of interstitial fibrosis, which in turn, leads to loss of renal function. However, the molecular mechanisms that link tubular cells to the interstitial compartment are not clear. Activation of the Stat3 transcription factor has been reported in tubular cells after renal damage, and Stat3 has been implicated in CKD progression. Here, we combined an experimental model of nephron reduction in mice from different genetic backgrounds and genetically modified animals with in silico and in vitro experiments to determine whether the selective activation of Stat3 in tubular cells is involved in the development of interstitial fibrosis. Nephron reduction caused Stat3 phosphorylation in tubular cells of lesion-prone mice but not in resistant mice. Furthermore, specific deletion of Stat3 in tubular cells significantly reduced the extent of interstitial fibrosis, which correlated with reduced fibroblast proliferation and matrix synthesis, after nephron reduction. Mechanistically, in vitro tubular Stat3 activation triggered the expression of a specific subset of paracrine profibrotic factors, including Lcn2, Pdgfb, and Timp1. Together, our results provide a molecular link between tubular and interstitial cells during CKD progression and identify Stat3 as a central regulator of this link and a promising therapeutic target.
NHS data sharing deal with Google prompts concern
Authors: Nigel Hawkes
Journal: BMJ (2016)

Privacy campaigners have criticised a data sharing agreement between the Royal Free Hospital in London and Google’s artificial intelligence subsidiary, DeepMind.

Under the deal, DeepMind would have access to five years’ of patient data—provided in accordance with NHS England’s information governance rules—as part of a project to improve the detection of acute kidney injury.

The project was not research but clinical care. DeepMind would use the data to drive a smartphone app called Streams which aimed to provide almost instant information about any patient whose blood tests showed evidence of kidney failure. The patient data campaign group MedConfidential questioned why Google needed so much data.

Phil …
Structural Basis of Diverse Homophilic Recognition by Clustered α- and β-Protocadherins
Authors: Kerry Marie Goodman, Rotem Rubinstein, Chan Aye Thu, Fabiana Bahna, Seetha Mannepalli, Göran Ahlsén, Chelsea Rittenhouse, Tom Maniatis, Barry Honig, Lawrence Shapiro
Journal: Neuron (2016)
Eligibility and Coverage Trends in Employer-Sponsored Insurance
Authors: Michelle Long, Matthew Rae, Gary Claxton, Anne Jankiewicz, David Rousseau
Journal: JAMA (2016)

This Visualizing Health Policy infographic looks at eligibility and coverage trends in employer-sponsored health insurance. Since 2000, the share of workers covered by employers’ health benefits at both offering and nonoffering firms has dropped to 56%, with the biggest decrease among employees working for small firms (3-199 workers). Among people younger than 65 years, those with lower incomes continued to be less likely to have coverage from an employer-sponsored health plan, as has been the trend since 1999. In 2015, larger firms were more likely than smaller ones to offer health benefits, as were organizations with more higher-wage employees, fewer lower-wage employees, and fewer workers 26 years or younger. Most large employers offered coverage to spouses and other dependents, while fewer than half of these firms offered coverage to same-sex or opposite-sex domestic partners. Few firms took action in 2015 in response to the Affordable Care Act’s employer mandate, including changing some jobs from part-time to full-time so employees would be eligible for coverage.
Hemoglobin St Mary's
Authors: Barbara J. Wild, Lorraine O. Phelan, Barbara J. Bain
Journal: American Journal of Hematology (2016)

A 5-year-old English girl presented with anemia. A complete blood count showed RBC 3.85 × 1012/l, hemoglobin concentration (Hb) 87 g/l, MCV 81 fl, MCH 22.5 pg, MCHC 278 g/l, red cell distribution width 25.7, and reticulocyte count 443 × 109/l (11.5%). Her blood film showed irregularly contracted cells and basophilic stippling (images). There were also polychromatic macrocytes, occasional cells with hemoglobin retracted to one side of the cell and occasional cells with siderotic granules. There was no history of exposure to drugs or other oxidants. Further tests were, therefore, done. High performance liquid chromatography (HPLC) on a BioRad variant instrument showed a peak in the hemoglobin S window (retention time 4.6 min) measuring 7.4%. No abnormal band was apparent on cellulose acetate electrophoresis at alkaline pH or agarose gel electrophoresis at acid pH. However on isoelectric focusing a variant hemoglobin was identified, which separated from hemoglobin A and comprised about half of the total hemoglobin. A heat test for an unstable hemoglobin was positive. Electrospray tandem mass spectrometry identified a novel hemoglobin variant, β101(Glu→Ala), which we designated hemoglobin St Mary's 1, subsequently also referred to as hemoglobin Youngstown. Bone marrow examination showed dyserythropoiesis and 30% ring sideroblasts. Her father, who had an Hb of 143 g/l, a reticulocyte count of 93 × 109/l and smaller numbers of irregularly contracted cells, was found to be a carrier of the same variant hemoglobin. The explanation for the low percentage abnormal peak on HPLC is that this represents denatured hemoglobin St Mary's, the intact variant hemoglobin having the same retention time as hemoglobin A. Irregularly contracted cells suggest a limited range of diagnostic possibilities: defects of the pentose shunt, exposure to endogenous or exogenous oxidants, or a hemoglobinopathy (hemoglobin C, hemoglobin E or an unstable hemoglobin). Small numbers can also be seen in β thalassemia heterozygosity. Dyserythropoiesis can be a feature of a hemoglobinopathy.
Sex differences in neuropsychological functioning among schizophrenic patients
Authors: R R Lewine, E F Walker, R Shurett, J Caudle, C Haden
Journal: American Journal of Psychiatry (1996)

The view of schizophrenic men as having poorer premorbid development, earlier age at onset, and worse outcome than schizophrenic women predicts greater neuropsychological impairment in the former than the latter. The authors examined in detail neuropsychological functioning in a large group of schizophrenic patients and a healthy comparison group.Neuropsychological functioning in 132 male and 63 female patients with schizophrenia or schizoaffective disorder was extensively studied and compared with that of 99 (40 male, 59 female) healthy individuals.As expected, the schizophrenic patients as a group were pervasively and significantly more impaired than the comparison group. Within schizophrenia, in contrast to the prediction, women performed significantly more poorly than men in verbal memory, spatial memory, and visual processing. Female schizophrenic patients also had significantly poorer right than left hemisphere performance, whereas male schizophrenic patients had identical scores for right and left hemisphere impairment.The findings are consistent with the hypothesis that schizophrenia among women may be partially understood as a right hemisphere dysfunction. Sampling, diagnostic, and epidemiologic factors may have affected the results.
Seasonal Influenza Infections and Cardiovascular Disease Mortality
Authors: Jennifer L. Nguyen, Wan Yang, Kazuhiko Ito, Thomas D. Matte, Jeffrey Shaman, Patrick L. Kinney
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> Cardiovascular deaths and influenza epidemics peak during winter in temperate regions. <h3>Objectives</h3> To quantify the temporal association between population increases in seasonal influenza infections and mortality due to cardiovascular causes and to test if influenza incidence indicators are predictive of cardiovascular mortality during the influenza season. <h3>Design, Setting, and Participants</h3> Time-series analysis of vital statistics records and emergency department visits in New York City, among cardiovascular deaths that occurred during influenza seasons between January 1, 2006, and December 31, 2012. The 2009 novel influenza A(H1N1) pandemic period was excluded from temporal analyses. <h3>Exposures</h3> Emergency department visits for influenza-like illness, grouped by age (≥0 years and ≥65 years) and scaled by laboratory surveillance data for viral types and subtypes, in the previous 28 days. <h3>Main Outcomes and Measures</h3> Mortality due to cardiovascular disease, ischemic heart disease, and myocardial infarction. <h3>Results</h3> Among adults 65 years and older, who accounted for 83.0% (73 363 deaths) of nonpandemic cardiovascular mortality during influenza seasons, seasonal average influenza incidence was correlated year to year with excess cardiovascular mortality (Pearson correlation coefficients ≥0.75,<i>P</i> ≤ .05 for 4 different influenza indicators). In daily time-series analyses using 4 different influenza metrics, interquartile range increases in influenza incidence during the previous 21 days were associated with an increase between 2.3% (95% CI, 0.7%-3.9%) and 6.3% (95% CI, 3.7%-8.9%) for cardiovascular disease mortality and between 2.4% (95% CI, 1.1%-3.6%) and 6.9% (95% CI, 4.0%-9.9%) for ischemic heart disease mortality among adults 65 years and older. The associations were most acute and strongest for myocardial infarction mortality, with each interquartile range increase in influenza incidence during the previous 14 days associated with mortality increases between 5.8% (95% CI, 2.5%-9.1%) and 13.1% (95% CI, 5.3%-20.9%). Out-of-sample prediction of cardiovascular mortality among adults 65 years and older during the 2009-2010 influenza season yielded average estimates with 94.0% accuracy using 4 different influenza metrics. <h3>Conclusions and Relevance</h3> Emergency department visits for influenza-like illness were associated with and predictive of cardiovascular disease mortality. Retrospective estimation of influenza-attributable cardiovascular mortality burden combined with accurate and reliable influenza forecasts could predict the timing and burden of seasonal increases in cardiovascular mortality.
IKZF1 deletions Are Detected In 40.3% Of 270 Adult B-Precursor-ALL and Are Independently Associated With BCR-ABL1 Positivity and Inferior Outcome
Authors: Annette Fasan, Claudia Haferlach, Madlen Ulke, Wolfgang Kern, Torsten Haferlach, Susanne Schnittger
Journal: Blood (2013)
Clinical and electrocardiographic characteristics of responders and nonresponders to class IA antiarrhythmic drugs.
Authors: Hirotsugu Atarashi, Nouko Kawaguchi, Masamichi Gotoh, Hirokazu Hayakawa
Journal: Circulation (1988)

A retrospective analysis of 44 patients was carried out to evaluate the efficacy of class IA antiarrhythmic drugs (disopyramide and/or procainamide), and of drugs of one or more other classes by means of 24-hour Holter recording. This study included only patients who exhibited 5000 or more ventricular premature complexes (VPCs) during a 24-hour pretrial baseline recording. The drugs that reduced the frequency of VPCs by at least 50% were considered effective. Eighteen patients (41%) responded to class IA drugs (responders) and 26 patients (59%) did not (nonresponders). There was a significant difference between the two groups in relation to the types of disease (p less than 0.01), but no significant difference with regard to other clinical and electrocardiographic characteristics. There was a significant discordance between trials of class IA drugs and class IC drugs (p less than 0.05). The efficacy of class IA drugs is very similar to that of class IB drugs, and only class IC drugs represent the highest efficacy in patients refractory to both class IA and class IB drugs. In conclusion, when ventricular arrhythmias do not respond to class IA or IB drugs, class IC drugs could be chosen as the next regimen.
Implementation of a Regional Telephone Cardiopulmonary Resuscitation Program and Outcomes After Out-of-Hospital Cardiac Arrest
Authors: Bentley J. Bobrow, Daniel W. Spaite, Tyler F. Vadeboncoeur, Chengcheng Hu, Terry Mullins, Wayne Tormala, Christian Dameff, John Gallagher, Gary Smith, Micah Panczyk
Journal: JAMA Cardiology (2016)

Bystander cardiopulmonary resuscitation (CPR) significantly improves survival from out-of-hospital cardiac arrest but is provided in less than half of events on average. Telephone CPR (TCPR) can significantly increase bystander CPR rates and improve clinical outcomes.To investigate the effect of a TCPR bundle of care on TCPR process measures and outcomes.A prospective, before-after, observational study of adult patients with out-of-hospital cardiac arrest not receiving bystander CPR before the 9-1-1 call between October 1, 2010, and September 30, 2013.A TCPR program, including guideline-based protocols, telecommunicator training, data collection, and feedback, in 2 regional dispatch centers servicing metropolitan Phoenix, Arizona. Audio recordings of out-of-hospital cardiac arrest calls were audited and linked with emergency medical services and hospital outcome data.Survival to hospital discharge and functional outcome at hospital discharge.There were 2334 out-of-hospital cardiac arrests (798 phase 1 [P1] and 1536 phase 2 [P2]) in the study group; 64% (1499) were male, and the median age was 63 years (age range, 9-101 years; interquartile range, 51-75 years). Provision of TCPR increased from 43.5% in P1 to 52.8% in P2 (P < .001), yielding an increase of 9.3% (95% CI, 4.9%-13.8%). The median time to first chest compression decreased from 256 seconds in P1 to 212 seconds in P2 (P < .001). All rhythm survival was significantly higher in P2 (184 of 1536 [12.0%]) compared with P1 (73 of 798 [9.1%]), with an adjusted odds ratio (aOR) of 1.47 (95% CI, 1.08-2.02; P = .02) in a logistic regression model and an adjusted difference in absolute survival rates (adjusted rate difference) of 3.1% (95% CI, 1.5%-4.9%). Survival for patients with a shockable initial rhythm significantly improved in P2 (107 of 306 [35.0%]) compared with P1 (42 of 170 [24.7%]), with an aOR of 1.70 (95% CI, 1.09-2.65; P = .02) and an adjusted rate difference of 9.6% (95% CI, 4.8%-14.4%). The rate of favorable functional outcome was significantly higher in P2 (127 of 1536 [8.3%]; 95% CI, 6.9%-9.8%) than in P1 (45 of 798 [5.6%]; 95% CI, 4.1%-7.5%), with an aOR of 1.68 (95% CI, 1.13-2.48; P = .01) and an adjusted rate difference of 2.7% (95% CI, 1.3%-4.4%).Implementation of a guideline-based TCPR bundle of care was independently associated with significant improvements in the provision and timeliness of TCPR, survival to hospital discharge, and survival with favorable functional outcome.
A Phase I Study of Lde225 in Combination with Docetaxel in Patients with Triple Negative (Tn) Advanced Breast Cancer (Abc): Geicam/2012-12
Authors: M. Martin, M. Ruiz-Borrego, J.M. Trigo, S. Antolin, J.A. Garcia Saenz, A. Hernando, A. Ocana, F. Rojo, S. López-Tarruella, L. Paz-Ares, N. Ribelles, L. Calvo, F. Moreno, R. Caballero, E. Carrasco
Journal: Annals of Oncology (2014)