tbuckley/cabot-search huggingface dataset:
Prospective Study Using the Risk of Ovarian Cancer Algorithm to Screen for Ovarian Cancer
Authors: Usha Menon, Steven J. Skates, Sara Lewis, Adam N. Rosenthal, Barnaby Rufford, Karen Sibley, Nicola MacDonald, Anne Dawnay, Arjun Jeyarajah, Robert C. Bast, David Oram, Ian J. Jacobs
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile. Patients and Methods Postmenopausal women, ≥ 50 years were randomly assigned to a control group or screen group. Screening involved serum CA125, interpreted using the ROC algorithm. Participants with normal results returned to annual screening; those with intermediate results had repeat CA125 testing; and those with elevated values underwent transvaginal ultrasound (TVS). Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion. Results Thirteen thousand five hundred eighty-two women were recruited. Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer (EOC). The specificity and positive predictive value (PPV) for primary invasive EOC were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively. Conclusion An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women.
Protein kinase C-η controls CTLA-4–mediated regulatory T cell function
Authors: Kok-Fai Kong, Guo Fu, Yaoyang Zhang, Tadashi Yokosuka, Javier Casas, Ann J Canonigo-Balancio, Stephane Becart, Gisen Kim, John R Yates, Mitchell Kronenberg, Takashi Saito, Nicholas R J Gascoigne, Amnon Altman
Journal: Nature Immunology (2014)
A physiological approach to the assessment of disease activity in rheumatoid arthritis
Authors: E. J. Goetzi, K. H. Falchuk, L. S. Zeiger, A. L. Sullivan, C. L. Hebert, J. P. Adams, J. L. Decker
Journal: Journal of Clinical Investigation (1971)

A method is described for assessing the in vivo oxygen consumption and lactate production rates of human knee joints. It is based on the rate of fall of P(o2) and the rate of rise in lactate concentration in an intra-articular saline pool after interruption of the circulation to the joint with an arterial tourniquet. Studies in 5 control patients with degenerative joint disease and 29 patients with rheumatoid arthritis showed a 2- to 3-fold higher mean oxygen uptake rate and a 10- to 12-fold higher mean lactate appearance rate in the saline in the rheumatoid joints with severe disease compared to the control joints. These metabolic variables correlated with tissue metabolic demand as estimated in synovial biopsies. (133)Xe washout from the intra-articular space, which reflects joint circulatory flow, showed a 3-fold greater mean washout rate from the rheumatoid joints (48 studies) than control joints (7 studies) with extensive overlap between the two groups. (133)Xe washout rate correlated with knee joint inflammation estimated both clinically and histologically. After synovectomy in four patients, the operated knee showed a greater fall in lactate production than the opposite knee in three of these patients. Neither knee joint oxygen uptake nor (133)Xe washout rate changed significantly. Intra-articular corticosteroid injection (eight patients) resulted in decreased lactate production and a decreased (133)Xe washout rate in the injected knee and variable results in the untreated knee. Oxygen uptake again was unchanged after therapy.
Cecal ligation and puncture induced sepsis impairs host defense against Enterococcus faecium peritonitis
Authors: Masja Leendertse, Rob J. Willems, Ida A. Giebelen, Sandrine Florquin, Petra S. van den Pangaart, Marc J. Bonten, Tom van der Poll
Journal: Intensive Care Medicine (2009)

Multiresistant and vancomycin resistant Enterococcus faecium (VRE) can cause serious infections in hospitalized patients with various co-morbid diseases. We investigated the course of VRE peritonitis after cecal ligation and puncture (CLP)-induced sepsis and compared this to sham operated mice.Mice were subjected to CLP or sham surgery. Forty-eight hours thereafter four groups were created by subjecting mice to peritoneal injection of either VRE or saline.Mice infected with VRE after CLP were severely impaired in eliminating VRE from the peritoneal cavity and distant body sites. These mice failed to mount an early inflammatory response at the primary site of VRE infection. VRE superinfection did not influence CLP-induced organ damage or polymicrobial bacterial loads.Sublethal polymicrobial sepsis greatly facilitates infection and dissemination of VRE. VRE does not influence the course of CLP-induced sepsis.
Pulmonary blastoma: a case report
Authors: K. M. Rao, R. P. Gupta, P. B. Das, S. John, A. Walter
Journal: Thorax (1974)

<b>Rao, K. M., Gupta, R. P., Das, P. B., John, S., and Walter, A. (1974).</b><i>Thorax</i>, <b>29</b>, 138-141. <b>Pulmonary blastoma.</b> A case report of a pulmonary blastoma is presented. A tumour was suspected at surgery and on histological examination this proved to be a pulmonary blastoma. A short review of the histogenesis and methods of treatment is given.
Phase I/II study of paclitaxel, gemcitabine and vinorelbine as first-line chemotherapy of non-small-cell lung cancer
Authors: V. Lorusso, E. Crucitta, N. Panza, N. Silvestris, M. Guida, F. Carpagnano, S. Mancarella, D. Sambiasi, M. De Lena
Journal: Annals of Oncology (2002)

The aim of our study was to determine the maximum tolerated dose of paclitaxel combined with a fixed dose of gemcitabine and vinorelbine in the treatment of non-small-cell lung cancer (NSCLC) and to evaluate in a phase II trial the efficacy of this combination.Sixty-two patients with stage IIIB/IV NSCLC were treated with paclitaxel in escalating doses from 40-80 mg/m(2) combined with gemcitabine and vinorelbine at fixed doses of 1000 mg/m(2) and 25 mg/m(2), respectively. All drugs were given intravenously on day 1 and 8 every 3 weeks.In a phase I trial, carried out on 21 patients, grade 4 neutropenia, as dose-limiting toxicity, occurred at the dosage level of paclitaxel 80 mg/m(2). In a phase II trial, with paclitaxel administered at 70 mg/m(2), 27 out of 41 (66%) assessable patients responded (10% complete responses and 56% partial responses). Objective response was observed in 13 of 16 patients (81%) with stage IIIB disease and in 14 of 25 (56%) with stage IV disease. The median time to treatment failure was 26 weeks (range 3-72 weeks; 32 weeks and 20 weeks for stages IIIB and IV, respectively) and median survival 62 weeks (range 4-176 weeks; 72 weeks and 56 weeks for stages IIIB and IV, respectively). One-year survival was 64% for all patients (72% for patients with stage IIIB and 52% for those with stage IV). Grade 3 and 4 neutropenia were observed in 11 (27%) and seven (17%) cases, respectively; grade 3 thrombocytopenia was observed in three patients (7%) and grade 3 anemia in four patients (10%). The most relevant non-hematological toxicity was grade 2/3 asthenia, which was observed in 12 patients (29%). Alopecia was almost universal, whereas nausea and vomiting were absent.The combination of paclitaxel, gemcitabine and vinorelbine is effective and tolerable in the treatment of NSCLC. The high activity and low toxicity of this regimen warrant randomized studies with platinum-containing combinations.
American Founder Mutation for Attenuated Familial Adenomatous Polyposis
Authors: Deborah W. Neklason, Jeffery Stevens, Kenneth M. Boucher, Richard A. Kerber, Nori Matsunami, Jahn Barlow, Geraldine Mineau, Mark F. Leppert, Randall W. Burt
Journal: Clinical Gastroenterology and Hepatology (2007)
Alcohol Consumption Induces Endogenous Opioid Release in the Human Orbitofrontal Cortex and Nucleus Accumbens
Authors: Jennifer M. Mitchell, James P. O’Neil, Mustafa Janabi, Shawn M. Marks, William J. Jagust, Howard L. Fields
Journal: Science Translational Medicine (2012)

Excessive consumption of alcohol is among the leading causes of preventable death worldwide. Although ethanol modulates a variety of molecular targets, including several neurotransmitter receptors, the neural mechanisms that underlie its rewarding actions and lead to excessive consumption are unknown. Studies in animals suggest that release of endogenous opioids by ethanol promotes further consumption. To examine this issue in humans and to determine where in the brain endogenous opioids act to promote alcohol consumption, we measured displacement of a radiolabeled μ opioid receptor agonist, [¹¹C]carfentanil, before and immediately after alcohol consumption in both heavy drinkers and control subjects. Drinking alcohol induced opioid release in the nucleus accumbens and orbitofrontal cortex, areas of the brain implicated in reward valuation. Opioid release in the orbitofrontal cortex and nucleus accumbens was significantly positively correlated. Furthermore, changes in orbitofrontal cortex binding correlated significantly with problem alcohol use and subjective high in heavy drinkers, suggesting that differences in endogenous opioid function in these regions contribute to excessive alcohol consumption. These results also suggest a possible mechanism by which opioid antagonists such as naltrexone act to treat alcohol abuse.
Clinical COPD questionnaire (CCQ) score and mortality
Authors: Josefin Sundh, Christer Janson, Karin Lisspers, Scott Montgomery, Björn Ställberg
Journal: European Respiratory Journal (2011)

Introduction:  Quality of life is an important patient-oriented measure in COPD. The Clinical COPD Questionnaire (CCQ) is a validated instrument for estimating health status, correlating well with instruments such as SGRQ and SF-36. The prognostic qualities of CCQ have not been evaluated. This study investigated the association of CCQ with all-cause mortality in COPD patients.   Methods:  A total of 1548 patients with a diagnosis of COPD were randomly selected from 70 Swedish primary and secondary care centres. The analysis included 956 patients (aged 34-75 years). Information was collected using questionnaires and record review. The Swedish Board of Health and Welfare provided mortality data. Cox regression estimated survival with adjustment for age, sex, smoking, education, level of care, and lung function (only available for a subset with spirometry data, n=491).   Results:  Over five years, 216 patients (22.6%) died. In patients with CCQ ≥3 indicating very severely limited health, mortality risk was statistically significantly higher than in stable COPD patients with mean CCQ    Conclusion:  In addition to health status, CCQ has prognostic qualities relevant to mortality in COPD patients, even after adjustment for lung function.
Mutant Sodium Channel for Tumor Therapy
Authors: Bakhos A Tannous, Adam P Christensen, Lisa Pike, Thomas Wurdinger, Katherine F Perry, Okay Saydam, Andreas H Jacobs, Jaime García-Añoveros, Ralph Weissleder, Miguel Sena-Esteves, David P Corey, Xandra O Breakefield
Journal: Molecular Therapy (2009)

Viral vectors have been used to deliver a wide range of therapeutic genes to tumors. In this study, a novel tumor therapy was achieved by the delivery of a mammalian brain sodium channel, ASIC2a, carrying a mutation that renders it constitutively open. This channel was delivered to tumor cells using a herpes simplex virus-1/Epstein-Barr virus (HSV/EBV) hybrid amplicon vector in which gene expression was controlled by a tetracycline regulatory system (tet-on) with silencer elements. Upon infection and doxycycline induction of mutant channel expression in tumor cells, the open channel led to amiloride-sensitive sodium influx as assessed by patch clamp recording and sodium imaging in culture. Within hours, tumor cells swelled and died. In addition to cells expressing the mutant channel, adjacent, noninfected cells connected by gap junctions also died. Intratumoral injection of HSV/EBV amplicon vector encoding the mutant sodium channel and systemic administration of doxycycline led to regression of subcutaneous tumors in nude mice as assessed by in vivo bioluminescence imaging. The advantage of this direct mode of tumor therapy is that all types of tumor cells become susceptible and death is rapid with no time for the tumor cells to become resistant.
Partial Lipodystrophy, Polycystic Ovary Syndrome and Proteinuria: A Common Link to Insulin Resistance?
Authors: V C Blackwell, P Salis, R W Groves, S E Baldeweg, G S Conway, R J Unwin
Journal: Journal of the Royal Society of Medicine (2001)

Insulin resistance is emerging as a key, and possibly primary, abnormality in a variety of seemingly unrelated diseases1.
Transcriptional Pathway Signatures Predict MEK Addiction and Response to Selumetinib (AZD6244)
Authors: Jonathan R. Dry, Sandra Pavey, Christine A. Pratilas, Chris Harbron, Sarah Runswick, Darren Hodgson, Christine Chresta, Rose McCormack, Natalie Byrne, Mark Cockerill, Alexander Graham, Garry Beran, Andrew Cassidy, Carolyn Haggerty, Helen Brown, Gillian Ellison, Judy Dering, Barry S. Taylor, Mitchell Stark, Vanessa Bonazzi, Sugandha Ravishankar, Leisl Packer, Feng Xing, David B. Solit, Richard S. Finn, Neal Rosen, Nicholas K. Hayward, Tim French, Paul D. Smith
Journal: Cancer Research (2010)

Selumetinib (AZD6244, ARRY-142886) is a selective, non-ATP-competitive inhibitor of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-1/2. The range of antitumor activity seen preclinically and in patients highlights the importance of identifying determinants of response to this drug. In large tumor cell panels of diverse lineage, we show that MEK inhibitor response does not have an absolute correlation with mutational or phospho-protein markers of BRAF/MEK, RAS, or phosphoinositide 3-kinase (PI3K) activity. We aimed to enhance predictivity by measuring pathway output through coregulated gene networks displaying differential mRNA expression exclusive to resistant cell subsets and correlated to mutational or dynamic pathway activity. We discovered an 18-gene signature enabling measurement of MEK functional output independent of tumor genotype. Where the MEK pathway is activated but the cells remain resistant to selumetinib, we identified a 13-gene signature that implicates the existence of compensatory signaling from RAS effectors other than PI3K. The ability of these signatures to stratify samples according to functional activation of MEK and/or selumetinib sensitivity was shown in multiple independent melanoma, colon, breast, and lung tumor cell lines and in xenograft models. Furthermore, we were able to measure these signatures in fixed archival melanoma tumor samples using a single RT-qPCR-based test and found intergene correlations and associations with genetic markers of pathway activity to be preserved. These signatures offer useful tools for the study of MEK biology and clinical application of MEK inhibitors, and the novel approaches taken may benefit other targeted therapies.
First cluster of vancomycin-resistan Enterococcus faecalis isolates in Cyprus
Authors: G.L. Daikos, P. Triantafyllopoulou, V. Syriopoulou, D. Bakatzouni-Pieridou, M. Kontou, M. Theodoulou, P. Tofas, G. Petrikkos
Journal: Clinical Microbiology and Infection (2005)
Mechanism of action of organophosphorus and carbamate insecticides.
Authors: T R Fukuto
Journal: Environmental Health Perspectives (1990)

Organophosphorus and carbamate insecticides are toxic to insects and mammals by virtue of their ability to inactivate the enzyme acetylcholinesterase. This review addresses the mechanism of inhibition of acetylcholinesterase by organophosphorus and carbamate esters, focusing on structural requirements necessary for anticholinesterase activity. The inhibition of acetylcholinesterase by these compounds is discussed in terms of reactivity and steric effects. The role of metabolic activation or degradation in the overall intoxication process is also discussed.
Screening for major depressive disorder in adults with cerebral glioma: an initial validation of 3 self-report instruments
Authors: Alasdair G. Rooney, Shanne McNamara, Mairi Mackinnon, Mary Fraser, Roy Rampling, Alan Carson, Robin Grant
Journal: Neuro-Oncology (2012)

No depression screening tool is validated for use in cases of cerebral glioma. To address this, we studied the operating characteristics of the Hospital Anxiety and Depression Scale (Depression subscale) (HAD-D), the Patient Health Questionnaire–9 (PHQ-9), and the Distress Thermometer (DT) in glioma patients.We conducted a twin-center prospective observational cohort study of major depressive disorder (MDD), according to the Diagnostic and Statistical Manual, 4th edition, in adults with a new diagnosis of cerebral glioma receiving active management or “watchful waiting.” At each of 3 interviews over a 6-month period, patients completed the screening questionnaires and received a structured clinical interview to diagnose MDD. Internal consistency, area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value, and positive likelihood ratio were calculated. A maximum of 154 patients completed the DT, 133 completed the HAD-D, and 129 completed the PHQ-9. The HAD-D and PHQ-9 showed good internal consistency (α ≥ 0.77 at all timepoints). Median AUCs were 0.931 ± 0.074 for the HAD-D and 0.915 ± 0.055 for the PHQ-9. The optimal threshold was 7+ for the HAD-D, but 8+ had similar operating characteristics. There was no consistently optimal PHQ-9 threshold, but 10+ was optimal in the largest sample. The DT was inferior to the multi-item instruments. Clinicians can screen for depression in well-functioning glioma patients using the HAD-D at the existing recommended lower threshold of 8+, or the PHQ-9 at a threshold of 10+. Due to a modest positive predictive value of either instrument, patients scoring above these thresholds need a clinical assessment to diagnose or exclude depression.
Waist circumference and lung function parameters: The PLATINO study
Authors: Ana Maria B. Menezes, Fernando C. Wehrmeister, Rogelio Perez-Padilla, Maria V. Lopez, Adriana Muiño, Carlos Talamo, Maria Montes de Oca, Jose R. Jardim, Gonzalo Valdivia
Journal: European Respiratory Journal (2012)

Background: Obesity is a known risk factor for chronic diseases. Recently, studies have shown that abdominal fat, measured by waist circumference, rather than BMI, is a more important predictor for the development of non-communicable chronic diseases. Objective: To evaluate the association between waist circumference (WC) and lung function parameters among adults. Methods: A cross-sectional study was performed in five Latin America countries (Brazil, Chile, Mexico, Uruguay and Venezuela), named the PLATINO study. The data were collected between 2002 and 2004 among adults aged ≥40 years old. FVC and FEV1 were measured using spirometry pre and post bronchodilator. WC was measured by trained interviewers. Data analyses were performed using multiple linear regression models and were stratified by sex. Results: The correlation coefficients (r) between WC and FVC and FEV1 were negative, although for WC and FEV1/FVC the coefficients were positive. After adjusting for age, height, weight, BMI and smoking, the increase of 1 cm in WC decreased FEV1 by 0.018 liters [95%CI -0.023; -0.013] in males, and 0.009 liters [95%CI -0.011; -0.006] in females. For FVC, the results showed the same direction, but were more expressive (males β = -0.024 [95%CI -0.057; -0.018] and females β = -0.014 [95%CI -0.017; -0.011]). When we evaluated the predicted values for FEV1 and FVC, an inverse relationship with WC was also found. For FEV1/FVC, only females showed a direct relationship with WC (β = 0.066 [95%CI 0.018; 0.114]). Conclusion: WC has an inverse relationship with lung function parameters in both males and females adults in Latin America, constituting an important public health issue requiring interventions.
Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study
Authors: Florent de Vathaire, Chiraz El-Fayech, Faten Fedhila Ben Ayed, Nadia Haddy, Catherine Guibout, David Winter, Cécile Thomas-Teinturier, Cristina Veres, Angela Jackson, Hélène Pacquement, Martin Schlumberger, Mike Hawkins, Ibrahima Diallo, Odile Oberlin
Journal: The Lancet Oncology (2012)
Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial
Authors: JY Douillard, D Cunningham, AD Roth, M Navarro, RD James, P Karasek, P Jandik, T Iveson, J Carmichael, M Alakl, G Gruia, L Awad, P Rougier
Journal: The Lancet (2000)
The timing of glucocorticoid administration in rheumatoid arthritis
Authors: N. G. Arvidson, B. Gudbjornsson, A. Larsson, R. Hallgren
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process. <h3>METHODS</h3> 26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group. <h3>RESULTS</h3> Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P &lt;&lt; 0.001), joint pain (P &lt; 0.001), Lansbury index (P &lt;&lt; 0.001), Ritchie index (P &lt;&lt; 0.001), and morning serum concentrations of IL-6 (P &lt; 0.01). The other study group showed minor but significant effects on morning stiffness (P &lt; 0.05) and circulating concentrations of IL-6 (P &lt; 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups. <h3>CONCLUSIONS</h3> Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.