tbuckley/cabot-search huggingface dataset:
Clock-Cancer Connection in Non–Hodgkin's Lymphoma: A Genetic Association Study and Pathway Analysis of the Circadian Gene Cryptochrome 2
Authors: Aaron E. Hoffman, Tongzhang Zheng, Richard G. Stevens, Yue Ba, Yawei Zhang, Derek Leaderer, Chunhui Yi, Theodore R. Holford, Yong Zhu
Journal: Cancer Research (2009)

Circadian genes have the potential to influence a variety of cancer-related biological pathways, including immunoregulation, which may influence susceptibility to non-Hodgkin's lymphoma (NHL). However, few studies have examined the role of circadian genes in lymphomagenesis. The current study examined Cryptochrome 2 (CRY2), a core circadian gene and transcriptional repressor, as a potential circadian biomarker for NHL. We first performed genetic association analyses of tagging single nucleotide polymorphisms (SNP) in CRY2 and NHL risk using DNA samples from a population-based case-control study (n = 455 cases and 527 controls). Three SNPs were found to be significantly associated with risk of NHL when combining all subtypes [dbSNP IDs, odds ratios (ORs), and 95% confidence intervals: rs11038689, OR, 2.34 (1.28-4.27), P = 0.006; rs7123390, OR, 2.40 (1.39-4.13), P = 0.002; and rs1401417, OR, 2.97 (1.57-5.63, P = 0.001)]. Each of these associations remained significant when restricting the analysis to B-cell cases and when further restricting to follicular lymphomas. An analysis of CRY2 diplotypes confirmed these significant findings. To further determine the functional effect of CRY2, we silenced the gene in vitro and performed a whole genome expression microarray. A pathway-based analysis showed that genes significantly altered by CRY2 knockdown formed networks associated with immune response and hematologic system development. In addition, these genes were predicted to have significant effects on several disease processes, including cancer (B-H P = 3.75E(-9)) and hematologic disease (B-H P = 8.01E(-8)). In conclusion, both genetic association and functional analyses suggest that the circadian gene CRY2 may play an important role in NHL development.
Predicting blood lead concentrations from lead in environmental media.
Authors: K R Mahaffey
Journal: Environmental Health Perspectives (1998)

Policy statements providing health and environmental criteria for blood lead (PbB) often give recommendations on an acceptable distribution of PbB concentrations. Such statements may recommend distributions of PbB concentrations including an upper range (e.g., maximum and/or 90th percentile values) and central tendency (e.g., mean and/or 50th percentile) of the PbB distribution. Two major, and fundamentally dissimilar, methods to predict the distribution of PbB are currently in use: statistical analyses of epidemiologic data, and application of biokinetic models to environmental lead measurements to predict PbB. Although biokinetic models may include a parameter to predict contribution of lead from bone (PbBone), contemporary data based on chemical analyses of pediatric bone samples are rare. Dramatic decreases in environmental lead exposures over the past 15 years make questionable use of earlier data on PbBone concentrations to estimate a contribution of lead from bone; often used by physiologic modelers to predict PbB. X-ray fluorescent techniques estimating PbBone typically have an instrument-based quantitation limit that is too high for use with many young children. While these quantitation limits have improved during the late 1990s, PbBone estimates using an epidemiologic approach to describing these limits for general populations of children may generate values lower than the instrument's quantitation limit. Additional problems that occur if predicting PbB from environmental lead by biokinetic modeling include a) uncertainty regarding the fractional lead absorption by young children; b) questions of bioavailability of specific environmental sources of lead; and c) variability in fractional absorption values over a range of exposures. Additional sources of variability in lead exposures that affect predictions of PbB from models include differences in the prevalence of such child behaviors as intensity of hand-to-mouth activity and pica. In contrast with these sources of uncertainty and variability affecting physiologic modeling of PbB distributions, epidemiologic data reporting PbB values obtained by chemical analyses of blood samples avoid these problems but raise other issues about the validity of the representation of the subsample for the overall population of concern. State and local health department screening programs and/or medical evaluation of individual children provide PbB data that contribute to databases describing the impact of environmental sources on PbB. Overall, application of epidemiologic models involves fewer uncertainties and more readily reflects variability in PbB than does current state-of-the-art biokinetic modeling.
Pertuzumab: Optimizing HER2 Blockade
Authors: Otto Metzger-Filho, Eric P. Winer, Ian Krop
Journal: Clinical Cancer Research (2013)

Abstract Pertuzumab has been approved by the U.S. Food and Drug Administration for use in combination with trastuzumab and docetaxel for the first-line treatment of patients with advanced HER2-positive (HER2+) breast cancer. Pertuzumab is a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2 and inhibits heterodimerization of HER2 with other HER family members, including EGF receptor (EGFR), HER3, and HER4. The HER2–HER3 heterodimer is a robust activator of phosphoinositide 3-kinase (PI3K) pathway signaling and functions as the most transforming and mitogenic of the receptor complexes formed by the HER family of proteins; thus, blockade of HER2–HER3 likely represents the most relevant action of pertuzumab. In the seminal phase III study, patients with HER2+ metastatic breast cancer were randomized to receive trastuzumab and docetaxel, with or without pertuzumab: Addition of pertuzumab significantly prolonged progression-free survival with an increase of 6.1 months (12.4 vs. 18.5 months, respectively). In a subsequent analysis with 30 months of median follow-up, pertuzumab conferred a 34% reduction in the risk of mortality. Here, we review the mechanism of action of pertuzumab, the rationale for combining it with trastuzumab/pertuzumab, clinical data, and future directions for this work. Clin Cancer Res; 19(20); 5552–6. ©2013 AACR.
Orudis in Management of Rheumatoid Arthritis and Osteoarthrosis of the Hip: Comparison with Indomethacin
Authors: A. N. Gyory, M. Bloch, H. C. Burry, R. Grahame
Journal: BMJ (1972)

In double-blind cross-over studies in 46 patients with rheumatoid arthritis and in 42 patients with osteoarthrosis of the hip, Orudis—a new non-steroidal anti-inflammatory agent—has been shown to be well tolerated and to have comparable therapeutic efficacy with indomethacin when given in equal dosage. Side effects were less severe with Orudis. The results suggest that Orudis will prove valuable in the clinical management of rheumatic diseases.
Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo.
Authors: G Strassmann, M Fong, C E Freter, S Windsor, F D'Alessandro, R P Nordan
Journal: Journal of Clinical Investigation (1993)

Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an important cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Suramin prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin-treated mice. On the other hand, the drug is approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin inhibits the action of other factors/cytokines that may also participate in colon-26-mediated cachexia is not yet known.
Plaque Composition and Clinical Outcomes in Acute Coronary Syndrome Patients With Metabolic Syndrome or Diabetes
Authors: Steven P. Marso, Nestor Mercado, Akiko Maehara, Giora Weisz, Gary S. Mintz, John McPherson, François Schiele, Dariusz Dudek, Martin Fahy, Ke Xu, Alexandra Lansky, Barry Templin, Zhen Zhang, Bernard de Bruyne, Patrick W. Serruys, Gregg W. Stone
Journal: JACC. Cardiovascular imaging (2012)
Blood and neoplastic diseases. Treatment of the lymphomas.
Authors: G H Fairley, J E Freeman
Journal: BMJ (1974)

<h3>Abstract</h3> In single-cell RNA sequencing data, biological processes or technical factors may induce an overabundance of zero measurements. Existing probabilistic approaches to interpreting these data either model all genes as zero-inflated, or none. But the overabundance of zeros might be gene-specific. Hence, we propose the AutoZI model, which, for each gene, places a spike-and-slab prior on a mixture assignment between a negative binomial (NB) component and a zero-inflated negative binomial (ZINB) component. We approximate the posterior distribution under this model using variational inference, and employ Bayesian decision theory to decide whether each gene is zero-inflated. On simulated data, AutoZI outperforms the alternatives. On negative control data, AutoZI retrieves predictions consistent to a previous study on ERCC spike-ins and recovers similar results on control RNAs. Applied to several datasets and instances of the 10x Chromium protocol, AutoZI allows both biological and technical interpretations of zero-inflation. Finally, AutoZI’s decisions on mouse embyronic stem-cells suggest that zero-inflation might be due to transcriptional bursting.
PUVA keratosis
Authors: M.C.G. van Praag, J.N. Bouwes Bavinck, W. Bergman, F.R. Rosendaal, A.M. Mommaas, I. Bruynzeel, E. Scheffer, B.J. Vermeer, J.A. Bruijn
Journal: Journal of the American Academy of Dermatology (1993)
Doctors fail to grasp concept of concordance
Authors: C. White
Journal: BMJ (2003)

Doctors are not grasping the concept of concordance in prescribing, says a progress report from the Task Force on Medicines Partnership, published this week.

But the report also admits that there is widespread misunderstanding about what the term actually means.

The partnership, which includes healthcare professionals, academics, patients, and representatives from the drug industry and from the NHS, was set up in April 2001 by the Department of Health.

It aims to help patients get the most out of their medicines and to try to stem the huge immediate and long term costs incurred by the NHS when patients do not take prescribed drugs. More than £230m ($370m; €330m) worth of …
CHRONIC PURPURIC ERUPTION WITHOUT DEMONSTRABLE BLOOD CHANGES
Authors: JOHN H. ARNETT
Journal: JAMA (1923)

Much has been done in recent years to clarify our views regarding that interesting and rather unusual group of conditions formerly known as purpura. Hemophilia, scurvy and other diseases displaying a tendency to hemorrhage have been weeded out of the group; the coagulation phenomena have been the subject of much careful study, and yet purpura remains an ill-defined borderline condition between internal medicine and dermatology, about which considerable confusion still exists. The case here reported represents a rare if not unique disease, but is presented not so much on this account as because it throws some interesting sidelights on purpura as a whole.  REPORT OF CASE  History.  —Mrs. K., a schoolteacher, aged 25, of Irish and Scotch ancestry, seen Oct. 30, 1922, complained chiefly of spots on the skin and burning of the lower extremities. There was no history of any similar condition or undue tendency toward bleeding, on either
Schonlein-Henoch purpura associated with losartan treatment and presence of antineutrophil cytoplasmic antibodies of x specificity
Authors: M. Brouard, V. Piguet, P. Chavaz, L. Borradori
Journal: British Journal of Dermatology (2001)

Spitz naevus showing clinical features of both granuloma pyogenicum and pigmented naevusSir, Spitz naevus is a benign melanocytic lesion that shares many histological features with malignant melanoma. 1It is most common on the lower extremities and the face of children, and presents at birth only rarely.Spitz naevi most commonly appear as solitary, pinkish, asymptomatic, domeshaped, round to oval, firm nodules, most of which are lightcoloured and soft, and may be clinically diagnosed as granuloma pyogenicum, haemangioma or dermal naevus. 2 However, pigmented Spitz naevus, or the dark-coloured type, may be tan, brown, or even black, and thus should be differentiated from malignant melanoma and pigmented naevus. 2 A 16-month-old Korean boy presented with a 4-month history of a 0´5 Â 0´5 Â 0´5 cm pinkish-coloured eroded dome-shaped nodule arising on a 1´2 Â 0´5 cm congenital verrucous, blackish plaque on the left side of the chest (Fig. 1a).Excisional biopsy was performed.Microscopy of the pinkish nodule showed many clusters of atypical melanocytes and increased numbers of vessels in the oedematous dermis.
Acute Bilateral Basal Ganglia Lesions in Patients With Diabetic Uremia: An FDG-PET Study
Authors: Han-Cheng Wang, Jung Lung Hsu, Yeh-You Shen
Journal: Clinical Nuclear Medicine (2004)

Head CT and MRI show characteristic changes in the syndrome of acute bilateral basal ganglia lesions in patients with diabetic uremia. However, they do not provide further insight into the underlying pathophysiology. To further clarify the biologic mechanism of the syndrome, F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) was used in 2 patients.PET studies were performed in 2 diabetic uremic patients with acute movement disorders. The cerebral glucose metabolic rates in these 2 patients were compared with 11 normal age-matched controls. The images were further analyzed with statistical parametric mapping to identify regions of significant metabolic abnormality.The cases showed markedly reduced glucose metabolism in the bilateral basal ganglia, especially in the bilateral putamens, where the glucose uptake was nearly absent.FDG-PET correlates better with the clinical conditions and provides more pathophysiological information than head CT or MRI scans in bilateral basal ganglia lesions in patients with diabetic uremia. We propose that acute exacerbation of a long-term glucose utilization failure in the basal ganglia cells produced these lesions.
Relationship of serum IgE concentration to level and rate of decline of pulmonary function: the Normative Aging Study.
Authors: N. A. Shadick, D. Sparrow, G. T. O'Connor, D. DeMolles, S. T. Weiss
Journal: Thorax (1996)

BACKGROUND: Previous reports on the relationship between serum immunoglobulin E (IgE) concentration and the level and rate of decline of pulmonary function in the general population have produced conflicting results. The relationship between total serum IgE concentration and pulmonary function was therefore examined in 1078 men aged 41-86 years followed in the Normative Aging Study. METHODS: The serum IgE concentration determined at the start of the three year follow up period was examined in relation to both the level and longitudinal rate of decline of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC. RESULTS: In a cross sectional analysis restricted to subjects who had ever smoked cigarettes, multiple linear regression models indicated an inverse association between total serum IgE concentration and both FEV1 (beta = -0.090 1/log10 IU/ml; SE = 0.030; p &lt; 0.005) and FVC (beta = -0.110 1/log10 IU/ml; SE = 0.034; p &lt; 0.005) but not FEV1/FVC, after adjustment for age and height. This relationship persisted when individuals with diagnosed asthma or methacholine hyperresponsiveness were excluded. In subjects who had never smoked cigarettes the total serum IgE concentration was unrelated to spirometric indices. No association was observed in smokers or non-smokers between the serum IgE concentration measured at the beginning of the period of follow up and the decline in FEV1, FVC, or FEV1/FVC. CONCLUSION: Increased levels of serum IgE measured at the beginning of the follow up period are associated with lower levels of pulmonary function but are not predictive of an accelerated rate in the decline of pulmonary function among middle aged and older men.
Safety, Correlative Markers, and Clinical Results of Adjuvant Nivolumab in Combination with Vaccine in Resected High-Risk Metastatic Melanoma
Authors: Geoffrey T. Gibney, Ragini R. Kudchadkar, Ronald C. DeConti, Melissa S. Thebeau, Maria P. Czupryn, Leticia Tetteh, Cabell Eysmans, Allison Richards, Michael J. Schell, Kate J. Fisher, Christine E. Horak, H. David Inzunza, Bin Yu, Alberto J. Martinez, Ibrahim Younos, Jeffrey S. Weber
Journal: Clinical Cancer Research (2014)

The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients.
High Altitude Pulmonary Edema
Authors: John P. Kleiner
Journal: JAMA (1975)

Since its original description in the English literature 15 years ago, high altitude pulmonary edema (HAPE) has been the subject of many reports. The clinical and hemodynamic features of HAPE are now well recognized, but its underlying pathophysiology remains unclear. In this article, a case of HAPE is described and the clinical features, proposed pathogenesis, and treatment are discussed. (<i>JAMA</i>234:491-495, 1975)
ON THE RELATION OF PRODUCTS OF ACTIVATED LYMPHOCYTES TO CELL-MEDIATED CYTOLYSIS
Authors: Christopher S. Henney, Judith Gaffney, Barry R. Bloom
Journal: The Journal of Experimental Medicine (1974)

Experiments have been designed to test the hypothesis that soluble mediator production and T-cell-mediated cytotoxicity are necessarily related phenomena, and that soluble mediators may be involved in the mechanism of cytolysis. To this end, agents known to inhibit T-cell-mediated lysis in vitro have been studied for their effects on the production of two lymphocyte-derived mediators, lymphotoxin (LT) and migration inhibitory factor (MIF). A clear dissociation between mediator production and cell-mediated cytolysis was found using inhibitors of protein synthesis. Pactamycin and emetine, in doses of 10–7 M to 10–6 M, suppressed production of MIF and LT with only slight effect on killing of mastocytoma cells by immune T cells. On the other hand colchicine and vinblastine inhibited T-cell-mediated cytolysis in a dose-related manner but had no significant effect on either MIF or LT production, A striking dichotomy was also observed after augmentation of intracellular cyclic 3'5' adenosine monophosphate (cAMP) levels with cholera enterotoxin. Increased cAMP levels were associated with abrogation of direct lytic activity, but were without significant effect on MIF or LT production in guinea pigs or mice. These findings indicate that mediator production and direct lymphocyte-mediated cytolysis can be experimentally dissociated and represent independent cell-mediated immune functions.
Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method
Authors: Y. Hayashizaki, H. Shibata, S. Hirotsune, H. Sugino, Y. Okazaki, N. Sasaki, K. Hirose, H. Imoto, H. Okuizumi, M. Muramatsu, H. Komatsubara, T. Shiroishi, K. Moriwaki, M. Katsuki, N. Hatano, H. Sasaki, T. Ueda, N. Mise, N. Takagi, C. Plass, V.M. Chapman
Journal: Nature Genetics (1994)
Effect of doctors' ethnicity and country of qualification on prescribing patterns in single handed general practices: linkage of information collected by questionnaire and from routine data
Authors: P. S Gill, A. Dowell, C. M Harris
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objectives:</b> To test whether Asian general practitioners who qualified in the Indian subcontinent prescribe items more often, more expensive items, and fewer generic drugs than their British trained Asian and non-Asian counterparts. <b>Design:</b> Linkage study using data collected by questionnaire and from routine sources. <b>Setting:</b> General practices in England. <b>Subjects:</b> 155 single handed general practitioners: 42 Asian doctors qualified in United Kingdom (group 1), 58 white doctors qualified in United Kingdom (group 2), and 55 Asian doctors qualified in Indian subcontinent (group 3). <b>Main outcome measures:</b> Prescribing cost (cost per ASTRO-PU), prescribing frequency (number of items per ASTRO-PU), and generic prescribing (percentage of drugs prescribed that are generic). <b>Results:</b> Doctors in group 1 were significantly younger than those in the other groups and had a higher proportion of patients who were from deprived wards. There was no difference between the groups in the proportion of female doctors and total list size. After adjustment for confounding factors, there were no significant differences between the three groups for prescribing cost (16.58 (95% confidence interval 6.39 to 26.77) for group 1, 17.31 (6.92 to 27.69) for group 2, 17.80 (7.22 to 28.38) for group 3, P=0.55); prescribing frequency (6.58 (4.60 to 8.40), 6.45 (4.70 to 8.30), 7.89 (6.16 to 9.64), P=0.34); and generic prescribing (44.44 (38.95 to 49.93), 47.41 (42.12 to 52.70), 44.04 (38.75 to 49.33), P=0.37). <b>Conclusions:</b> Asian doctors qualified from the Indian subcontinent did not differ from British trained doctors in their prescribing practice. This study refutes the common belief that Asian doctors are high volume and high cost prescribers. <h3>Key messages</h3> There is anecdotal evidence that doctors from the Indian subcontinent issue more prescriptions and more expensive items that do non-Asian doctors We examined this claim by means of a linkage study using data from 155 single handed general practitioners and routine data sources There was no significant difference between Asian doctors qualified in the Indian subcontinent and British trained Asian and white doctors for prescribing costs, the number of items prescribed, and the percentage prescribing of generic drugs These results refute the myth that Asian doctors are high volume and high cost prescribers