tbuckley/cabot-search huggingface dataset:
Stage II Colon Cancer Prognosis Prediction by Tumor Gene Expression Profiling
Authors: Alain Barrier, Pierre-Yves Boelle, François Roser, Jennifer Gregg, Chantal Tse, Didier Brault, François Lacaine, Sidney Houry, Michel Huguier, Brigitte Franc, Antoine Flahault, Antoinette Lemoine, Sandrine Dudoit
Journal: Journal of Clinical Oncology (2006)

This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated.Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes.The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy.Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.
The impact of docetaxel-related toxicities on health-related quality of life in patients with metastatic cancer (QoliTax)
Authors: S.-E. Al-Batran, W. Hozaeel, F.K. Tauchert, R.-D. Hofheinz, A. Hinke, C. Windemuth-Kieselbach, A. Hübner, M. Burmester, M. Koenigsmann, J. Wiegand, G. zur Hausen, B. Linsse, R. Kuhl, C. Pauligk
Journal: Annals of Oncology (2015)
NHS staff are invited to see climate change film free of charge
Authors: A. O'Dowd
Journal: BMJ (2009)

All NHS staff will have the chance to see the film The Age of Stupid , about the consequences of climate change, free of charge thanks to investment from various organisations, including the BMJ .

The BMJ will also be hosting a webcast discussion of climate change and health on Tuesday 7 July at 1 pm, which has been prompted by the film and the issues it considers.

The webcast panel, chaired by Fiona Godlee, editor of the BMJ , will discuss the film’s conclusions and how much the NHS has to …
Non-resolving pneumonia in patient with obsessive–compulsive disorder
Authors: Sami O Simons, Evelien A J E Braam, Roline C de Boer, Monika Looijen-Salamon, Yvonne F Heijdra
Journal: Thorax (2013)

A 26-year-old woman presented with a history of chronic progressive dyspnoea and a non-productive cough. Her medical history revealed recurrent, unexplained pneumonias and treatment for anorexia nervosa. The patient was a lifelong non-smoker and she denied any use of toxic substances.

On examination, her vital signs were as follows: body mass index, 17.6 kg/m2; temperature, 38.4°C; heart rate, 102 beats/min; BP, 100/60 mm Hg; respiratory rate, 24 breaths/min; and oxygen saturation, 91% on 6 L/min oxygen by nasal cannula. On auscultation, decreased breath sounds were heard at the bases bilaterally.

Blood testing for antinuclear antibodies was negative and immunological analysis demonstrated no immunodeficiency. Pulmonary function tests showed a restrictive pattern (total lung capacity: 3.72 L, 73% of predicted). A CT scan of the chest revealed bilateral consolidations with air bronchograms and a tree-in-bud-pattern (figure 1). A bronchoscopy …
Induction of Multidrug Resistance in Human Cells by Transient Exposure to Different Chemotherapeutic Drugs
Authors: P. M. Chaudhary, I. B. Roninson
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : The MDR1 (multidrug resistance) gene (also known as PGY1), which encodes the transmembrane efflux pump P-glycoprotein (Pgp), confers resistance to Pgp-transported cytotoxic drugs in tissue culture. The increase in MDR1 expression in tumors after chemotherapy is usually attributed to selection of pre-existing multidrug-resistant cells by Pgp-transported drugs. MDR1 expression in tissue culture can be increased by several types of stress-inducing treatment, including agents that activate protein kinase C (PKC). Previous studies, however, failed to demonstrate that short-term exposure to any chemotherapeutic drug can induce the expression of the resident MDR1 gene in drug-sensitive human cells. Purpose : This study was designed to utilize highly sensitive assays to determine if transient exposure to chemotherapeutic drugs would have an effect on MDR1 expression in human cells and to assess if PKC inhibitors would influence such an effect Methods : We analyzed the MDR1 gene expression in several human cell lines derived from leukemias or solid tumors, after treatment with different cytotoxic drugs, in the presence or absence of PKC inhibitors. Pgp function and expression were studied by flow cytometric assays, and MDR1 messenger RNA (mRNA) was assayed by polymerase chain reaction. Results : Transient exposure to chemotherapeutic drugs, including agents that are not transported by Pgp, induced Pgp and MDR1 mRNA expression in subpopulations of treated cells in most of the tested cell lines. This induction was observed along with microscopically detectable cell damage. The drug-induced MDR1 expression and the associated twofold to threefold increase in resistance to vinblastine were sustained in K562 leukemia cells for at least several weeks after the removal of the drug. Drug-mediated MDR1 induction was blocked by nonspecific protein kinase inhibitors that are active against PKC, but not by a protein kinase inhibitor ineffective against PKC. Conclusions : Expression of the human MDR1 mRNA and Pgp can be induced in response to cellular damage by cytotoxic drugs regardless of whether the drugs are transported by Pgp. This induction can be prevented by protein kinase inhibitors. Implications : Induction of MDR1 expression in response to cellular damage may account for increased MDR1 expression in treated human tumors. Protein kinase inhibitors may be useful in preventing the emergence of multidrug resistance during cancer chemotherapy. [J Natl Cancer Inst 85:632-639, 1993]
Differences and similarities in rheumatology specialty training programmes across European countries
Authors: Francisca Sivera, Sofia Ramiro, Nada Cikes, Maxime Dougados, Laure Gossec, Tore K Kvien, Ingrid E Lundberg, Peter Mandl, Arumugam Moorthy, Sonia Panchal, José A P da Silva, Johannes W Bijlsma
Journal: Annals of the Rheumatic Diseases (2015)

To analyse the similarities and discrepancies between the official rheumatology specialty training programmes across Europe.A steering committee defined the main aspects of training to be assessed. In 2013, the rheumatology official training programmes were reviewed for each of the European League Against Rheumatism (EULAR) countries and two local physicians independently extracted data on the structure of training, included competencies and assessments performed. Analyses were descriptive.41 of the 45 EULAR countries currently provide specialist training in rheumatology; in the remaining four rheumatologists are trained abroad. 36 (88%) had a single national curriculum, one country had two national curricula and four had only local or university-specific curricula. The mean length of training programmes in rheumatology was 45 (SD 19) months, ranging between 3 and 72 months. General internal medicine training was mandatory in 40 (98%) countries, and was performed prior to and/or during the rheumatology training programme (mean length: 33 (19) months). 33 (80%) countries had a formal final examination.Most European countries provide training in rheumatology, but the length, structure, contents and assessments of these training programmes are quite heterogeneous. In order to promote excellence in standards of care and to support physicians' mobility, a certain degree of harmonisation should be encouraged.
Mortality Among High-Risk Patients With Acute Myocardial Infarction Admitted to US Teaching-Intensive Hospitals in July
Authors: Anupam B. Jena, Eric C. Sun, John A. Romley
Journal: Circulation (2013)

Studies of whether inpatient mortality in US teaching hospitals rises in July as a result of organizational disruption and relative inexperience of new physicians (July effect) find small and mixed results, perhaps because study populations primarily include low-risk inpatients whose mortality outcomes are unlikely to exhibit a July effect.Using the US Nationwide Inpatient sample, we estimated difference-in-difference models of mortality, percutaneous coronary intervention rates, and bleeding complication rates, for high- and low-risk patients with acute myocardial infarction admitted to 98 teaching-intensive and 1353 non-teaching-intensive hospitals during May and July 2002 to 2008. Among patients in the top quartile of predicted acute myocardial infarction mortality (high risk), adjusted mortality was lower in May than July in teaching-intensive hospitals (18.8% in May, 22.7% in July, P<0.01), but similar in non-teaching-intensive hospitals (22.5% in May, 22.8% in July, P=0.70). Among patients in the lowest three quartiles of predicted acute myocardial infarction mortality (low risk), adjusted mortality was similar in May and July in both teaching-intensive hospitals (2.1% in May, 1.9% in July, P=0.45) and non-teaching-intensive hospitals (2.7% in May, 2.8% in July, P=0.21). Differences in percutaneous coronary intervention and bleeding complication rates could not explain the observed July mortality effect among high risk patients.High-risk acute myocardial infarction patients experience similar mortality in teaching- and non-teaching-intensive hospitals in July, but lower mortality in teaching-intensive hospitals in May. Low-risk patients experience no such July effect in teaching-intensive hospitals.
Lung cGMP release subsequent to NO inhalation in pulmonary hypertension: responders<i>versus</i>nonresponders
Authors: H.A. Ghofrani, R. Wiedemann, F. Rose, N. Weissmann, R.T. Schermuly, K. Quanz, F. Grimminger, W. Seeger, H. Olschewski
Journal: European Respiratory Journal (2002)

Inhalation of nitric oxide (NO) is widely employed for the assessment of pulmonary vasoresponsiveness in pulmonary hypertension (PH). However, the reasons for the huge differences in vascular reactivity to NO between patients are unknown, and the role of NO-induced cyclic guanosine monophosphate (cGMP) is unclear. Twenty patients with severe precapillary PH were investigated. Thirty-six Swan-Ganz catheter investigations were performed and the study subjects were tested for responses to NO inhalation. This included an assessment of pulmonary and systemic arterial plasma cGMP and atrial natriuretic peptide (ANP) levels. A significant NO response (pulmonary vascular resistance (PVR) decrease &gt;20%) was noted in nine of 20 patients (45%) during the first catheterization. A highly significant correlation between baseline plasma cGMP and ANP levels with PVR was observed (r=0.62 and r=0.66, respectively; p&lt;0.0001). In response to NO, systemic and mixed venous cGMP levels increased from 13.9±1.28 nM and 12.75±0.99 nM to 79.23±4.99 nM and 55.25±4.41 nM (p&lt;0.001), respectively, accompanied by the appearance of a marked transpulmonary cGMP gradient. Although in the responder group ANP levels were significantly reduced after NO inhalation, no significant correlation was observed to the extent of PVR reduction. The magnitude of the NO-elicited cGMP response did not discriminate between haemodynamic responders and nonresponders. This study concludes that plasma cyclic guanosine monophosphate levels are significantly correlated with the severity of disease in pulmonary arterial hypertension. Nitric oxide inhalation provokes a prompt increase in cyclic guanosine monophosphate secretion, but the magnitude of this release is not linked with a decrease in pulmonary vascular resistance.
COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy
Authors: P. Hadji, C. Jackisch, W. Bolten, M. Blettner, H.J. Hindenburg, P. Klein, K. König, R. Kreienberg, W. Rief, D. Wallwiener, S. Zaun, N. Harbeck
Journal: Annals of Oncology (2013)
X-linked B-lymphocyte immune defect in CBA/N mice. II. Studies of the mechanisms underlying the immune defect.
Authors: I Scher, A D Steinberg, A K Berning, W E Paul
Journal: The Journal of Experimental Medicine (1975)

The mechanisms underlying the X-linked thymus-independent (B) lymphocyte functional defect in the CBA/N (CN) mice and their F1 progeny were studied. Immune defective mice were unable to respond to the T-independent antigen 2,4-dinitrophenyl-lysyl-derivative of Ficoll (DNP-lys-Ficoll) but were able to form antibody against the highly cross-reactive hapten (trinitrophenyl) when it was coupled to an erythrocyte carrier. Immune defective CN X DBA/2N (DN) F1 male mice, which do not normally respond to T-independent antigens, were able to respond to both polyribosinic-polyribocytidylic acid and DNP-lys-Ficoll after the administration of CN X DN F1 female spleen cells even if these cells had been depleted of T lymphocytes. In addition, it was shown that the inability of the CN mice and their F1 progeny to respond to T-independent antigens was not due to an intrinsic abnormality of their microenvironment or the suppressive actions of a T lymphocyte. Our data present evidence that the X-linked defect in the CN mice is due to an intrinsic defect in B-lymphocyte development.
Delirium in Mechanically Ventilated Patients
Authors: E. Wesley Ely, Sharon K. Inouye, Gordon R. Bernard, Sharon Gordon, Joseph Francis, Lisa May, Brenda Truman, Theodore Speroff, Shiva Gautam, Richard Margolin, Robert P. Hart, Robert Dittus
Journal: JAMA (2001)

OF consciousness characterized by an acute onset and fluctuating course of impaired cognitive functioning so that a patient's ability to receive, process, store, and recall information is strikingly impaired.7][18][19][20] In this population, cogni-
Long-Term Colorectal-Cancer Mortality after Adenoma Removal
Authors: Magnus Løberg, Mette Kalager, Øyvind Holme, Geir Hoff, Hans-Olov Adami, Michael Bretthauer
Journal: New England Journal of Medicine (2014)

Although colonoscopic surveillance of patients after removal of adenomas is widely promoted, little is known about colorectal-cancer mortality among these patients.Using the linkage of the Cancer Registry and the Cause of Death Registry of Norway, we estimated colorectal-cancer mortality among patients who had undergone removal of colorectal adenomas during the period from 1993 through 2007. Patients were followed through 2011. We calculated standardized incidence-based mortality ratios (SMRs) using rates for the Norwegian population at large for comparison. Norwegian guidelines recommended colonoscopy after 10 years for patients with high-risk adenomas (adenomas with high-grade dysplasia, a villous component, or a size ≥10 mm) and after 5 years for patients with three or more adenomas; no surveillance was recommended for patients with low-risk adenomas. Polyp size and exact number were not available in the registry. We defined high-risk adenomas as multiple adenomas and adenomas with a villous component or high-grade dysplasia.We identified 40,826 patients who had had colorectal adenomas removed. During a median follow-up of 7.7 years (maximum, 19.0), 1273 patients were given a diagnosis of colorectal cancer. A total of 398 deaths from colorectal cancer were expected and 383 were observed, for an SMR of 0.96 (95% confidence interval [CI], 0.87 to 1.06) among patients who had had adenomas removed. Colorectal-cancer mortality was increased among patients with high-risk adenomas (expected deaths, 209; observed deaths, 242; SMR, 1.16; 95% CI, 1.02 to 1.31), but it was reduced among patients with low-risk adenomas (expected deaths, 189; observed deaths, 141; SMR, 0.75; 95% CI, 0.63 to 0.88).After a median of 7.7 years of follow-up, colorectal-cancer mortality was lower among patients who had had low-risk adenomas removed and moderately higher among those who had had high-risk adenomas removed, as compared with the general population. (Funded by the Norwegian Cancer Society and others.).
Genomic analysis of early murine mammary gland development using novel probe-level algorithms.
Authors: Stephen R Master, Alexander J Stoddard, L Charles Bailey, Tien-Chi Pan, Katherine D Dugan, Lewis A Chodosh
Journal: Genome biology (2005)

Abstract We describe a novel algorithm (ChipStat) for detecting gene-expression changes utilizing probe-level comparisons of replicate Affymetrix oligonucleotide microarray data. A combined detection approach is shown to yield greater sensitivity than a number of widely used methodologies including SAM, dChip and logit-T. Using this approach, we identify alterations in functional pathways during murine neonatal-pubertal mammary development that include the coordinate upregulation of major urinary proteins and the downregulation of loci exhibiting reciprocal imprinting.
Pharmacogenetic basis for severe asthma exacerbations
Authors: Shoaib Faruqi
Journal: Thorax (2008)

Activation of CD23, a low affinity IgE receptor, results in downregulation of IgE-mediated immune responses. CD23 is encoded for by the Fc fragment of IgE low affinity II receptor (FCER2) gene. IgE levels may increase in children with asthma treated with inhaled corticosteroids, and this may be explained by a decrease in FCER2 expression by corticosteroids. Also, elevated IgE levels are …
Rare Cancers Europe (RCE) methodological recommendations for clinical studies in rare cancers: a European consensus position paper
Authors: P.G. Casali, P. Bruzzi, J. Bogaerts, J.-Y. Blay, M. Aapro, A. Adamous, A. Berruti, J.-Y. Blay, J. Bogaerts, J. Bressington, B. Bruzzi, R. Capocaccia, F. Cardoso, P.G. Casali, J.E. Celis, A. Cervantes, F. Ciardiello, C. Claussen, M. Coleman, S. Comis, S. Craine, D. De Boltz, F. De Lorenzo, A.P. Dei Tos, G. Gatta, J. Geissler, R. Giuliani, E. Grande, A. Gronchi, S. Jezdic, B. Jonsson, L. Jost, H. Keulen, D. Lacombe, G. Lamory, Y. Le Cam, S. Leto di Priolo, L. Licitra, F. Macchia, A. Margulies, S. Marreaud, G. McVie, S. Narbutas, K. Oliver, N. Pavlidis, J. Pelouchova, G. Pentheroudakis, M. Piccart, M.A. Pierotti, G. Pravettoni, K. Redmond, P. Riegman, M.P. Ruffilli, D. Ryner, S. Sandrucci, M. Seymour, V. Torri, A. Trama, S. Van Belle, G. Vassal, M. Wartenberg, C. Watts, A. Wilson, W. Yared
Journal: Annals of Oncology (2014)

While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to sequentially test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers.
Human sealpox resulting from a seal bite: confirmation that sealpox virus is zoonotic
Authors: C. Clark, P.G. McIntyre, A. Evans, C.J. McInnes, S. Lewis-Jones
Journal: British Journal of Dermatology (2005)

The case of a marine mammal technician who sustained a seal‐bite to the hand that produced a lesion clinically very similar to orf is described. Sequence analysis of the viral DNA amplified from the lesion by the polymerase chain reaction indicated that it was sealpox virus in origin. This is the first report providing unequivocal evidence that sealpox may be transmitted to humans and causes lesions very similar to orf.
The effect of salt chamber treatment on bronchial hyperresponsiveness in asthmatics
Authors: J. Hedman, T. Hugg, J. Sandell, T. Haahtela
Journal: Allergy (2006)

Background: Randomized controlled trials are needed to evaluate the effects of complementary treatments in asthma. This study assessed the effect of salt chamber treatment as an add‐on therapy to low to moderate inhaled steroid therapy in asthma patients with bronchial hyperresponsiveness (BHR). Methods: After a 2‐week baseline period, 32 asthma patients who exhibited BHR in the histamine inhalation challenge were randomized: 17 to 2‐week active treatment, during which salt was fed to the room by a salt generator, and 15 to placebo. The salt chamber treatment lasted 40 min and was administered five times a week. Results: Median provocative dose causing a decrease of 15% in Fev 1 (PD 15 FEV 4 ) increased significantly in the active group ( P = 0.047) but not in the placebo group. The difference in changes between the active and placebo groups was significant ( P = 0.02). Nine patients (56%) in the active group and two patients (17%) in the placebo group exhibited at least one doubling dose decrease in BHR ( P = 0.040). Six patients (38%) in the active group and none in the placebo group became non‐hyperresponsive ( P = 0.017). Neither the peak expiratory flow (PEF) values measured just before and after the treatment, nor FEV 1 values measured before the histamine challenges, changed. The reduction in BHR was not caused by changes in the baseline lung function. Conclusions: Salt chamber treatment reduced bronchial hyperresponsiveness as an add‐on therapy in asthmatics with a low to moderate dose of inhaled steroids. The possibility that salt chamber treatment could serve as a complementary therapy to conventional medication cannot be excluded.