tbuckley/cabot-search huggingface dataset:
CYP3A Variation, Premenopausal Estrone Levels, and Breast Cancer Risk
Authors: Nichola Johnson, Kate Walker, Lorna J. Gibson, Nick Orr, Elizabeth Folkerd, Ben Haynes, Claire Palles, Ben Coupland, Minouk Schoemaker, Michael Jones, Peter Broderick, Elinor Sawyer, Michael Kerin, Ian P. Tomlinson, Marketa Zvelebil, Sarah Chilcott-Burns, Katarzyna Tomczyk, Gemma Simpson, Jill Williamson, Stephen G. Hillier, Gillian Ross, Richard S. Houlston, Anthony Swerdlow, Alan Ashworth, Mitch Dowsett, Julian Peto, Isabel dos Santos Silva, Olivia Fletcher
Journal: JNCI Journal of the National Cancer Institute (2012)

Epidemiological studies have provided strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that are associated with hormone levels and the risk of breast cancer in premenopausal women. We measured urinary levels of estrone glucuronide (E1G) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle in 729 healthy premenopausal women. We genotyped 642 single-nucleotide polymorphisms (SNPs) in these women; a single SNP, rs10273424, was further tested for association with the risk of breast cancer using data from 10 551 breast cancer case patients and 17 535 control subjects. All statistical tests were two-sided. rs10273424, which maps approximately 50 kb centromeric to the cytochrome P450 3A (CYP3A) gene cluster at chromosome 7q22.1, was associated with a 21.8% reduction in E1G levels (95% confidence interval [CI] = 27.8% to 15.3% reduction; P = 2.7 × 10−9) and a modest reduction in the risk of breast cancer in case patients who were diagnosed at or before age 50 years (odds ratio [OR] = 0.91, 95% CI = 0.83 to 0.99; P = .03) but not in those diagnosed after age 50 years (OR = 1.01, 95% CI = 0.93 to 1.10; P = .82). Genetic variation in noncoding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and is associated with the risk of breast cancer in younger patients. This association may have wider implications given that the most predominantly expressed CYP3A gene, CYP3A4, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents used in the treatment of breast cancer.
Use of high resolution computed tomography of the lungs in patients with rheumatoid arthritis.
Authors: B Cortet, R M Flipo, M Remy-Jardin, P Coquerelle, B Duquesnoy, J Remy, B Delcambre
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To assess the usefulness of high resolution computed tomography (HRCT) of the lungs in patients with rheumatoid arthritis (RA) with and without respiratory symptoms. PATIENTS AND METHODS--Eighty eight RA patients with a mean duration of disease 12 (SD 8) years were evaluated. Eleven patients were excluded because of previous exposure to silica. The 77 remaining patients formed two groups according to the absence (group I, n = 38) or the presence (group II, n = 39) of chronic respiratory symptoms. A control group consisted of 51 non-smoking, healthy patients. RESULTS--The most frequent abnormalities observed in the 77 RA patients were bronchiectasis or bronchiolectasis (n = 23, 30%), pulmonary nodules (n = 17, 22%), subpleural micronodules or pseudoplaques (n = 13, 17%), ground glass opacities (n = 11, 14%), and honeycombing (n = 8, 10%). Bronchiectasis or bronchiolectasis (p = 0.012), rounded opacities (p = 0.016), ground glass attenuation (p = 0.004), and honeycombing (p = 0.002) were found more often in RA group II (with respiratory symptoms) than in group I (no respiratory symptoms). Non-linear septal opacities were more frequent in group I than in the control group, but other HRCT findings did not differ statistically significantly between group I and the control group. CONCLUSION--Bronchiectasis may be a characteristic lung change in RA patients. Abnormalities on HRCT are less frequently observed in the absence of respiratory symptoms than in the presence of such symptoms (29% versus 69%).
EIA and GC/MS analysis of 8-isoprostane in EBC of children with problematic asthma
Authors: S. Carraro, P. E. Cogo, I. Isak, M. Simonato, M. Corradi, V. P. Carnielli, E. Baraldi
Journal: European Respiratory Journal (2009)

Asthmatic airways are characterised by enhanced oxidative stress, which can be studied by measuring biomarkers, such as 8-isoprostane. The aims of the present study were: 1) to measure the concentrations of 8-isoprostane in exhaled breath condensate (EBC) and urine of children with problematic and well-controlled asthma; 2) to compare the concentrations of 8-isoprostane measured by gas chromatographic/negative ion chemical ionisation mass spectrometry (GC/NICI-MS) and by an enzymatic immunoassay (EIA). We recruited 20 asthmatic allergic children, 13 with well-controlled asthma and seven with problematic asthma. They underwent exhaled nitric oxide measurements and spirometry, and both EBC and urine samples were collected. 8-isoprostane was measured in EBC by GC/NICI-MS and EIA. 8-isoprostane concentrations in EBC were significantly higher in children with problematic asthma than in children with well-controlled asthma (p = 0.01). An acceptable reproducibility emerged between GC/NICI-MS and EIA (coefficient of reproducibility 11.5 pg·mL<sup>−1</sup>). 8-isoprostane levels measured in urine did not correlate with those measured in EBC. We showed that 8-isoprostane in EBC was significantly increased in children with problematic asthma, suggesting a role for oxidative stress in this asthma phenotype. In addition we found an acceptable reproducibility of EIA compared to GC/NICI-MS, even if the latter method had higher accuracy.
Use of induced sputum cell counts to investigate airway inflammation in asthma.
Authors: I Pin, P G Gibson, R Kolendowicz, A Girgis-Gabardo, J A Denburg, F E Hargreave, J Dolovich
Journal: Thorax (1992)

BACKGROUND: Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less invasive methods of obtaining sputum from patients unable to produce it spontaneously should provide a useful investigational tool in asthma. METHODS: A method to induce sputum with inhaled hypertonic saline was modified for use in 17 asthmatic patients and 17 normal subjects who could not produce sputum spontaneously. The success rate and safety of the method, the reproducibility of cell counts, and differences in cell counts between the asthmatic and normal groups were examined. Hypertonic saline solution 3-5% was inhaled for up to 30 minutes after inhalation of salbutamol. Subjects were asked to expectorate sputum every five minutes. The quality of the sample was scored on the volume of plugs and the extent of salivary contamination. Plugs from the lower respiratory tract were selected for a total cell count and for differential cell counts of eosinophils and metachromatic cells (mast cells and basophils) in direct smears. RESULTS: Adequate samples from the lower respiratory tract were obtained in 76% of first attempts. The mean fall in the forced expiratory volume in one second (FEV1) during inhalation of saline was 5.3% and the maximum fall 20%. Eosinophil and metachromatic cell counts were reproducible (reliability coefficient 0.8 and 0.7 respectively). When compared with sputum from normal subjects sputum from asthmatic patients contained a significantly higher proportion of eosinophils (mean 18.5% (SE 3.8%) v 1.9% (0.6%)) and metachromatic cells (0.50% (0.18%) v 0.039% (0.014%)). In the asthmatic group the differential eosinophil count correlated with the baseline FEV1. CONCLUSION: Induced sputum is capable of detecting differences in cell counts between normal and asthmatic subjects and merits further development as a potential means of assessing airway inflammation in asthma.
Targeted Marketing and Public Health
Authors: Sonya A. Grier, Shiriki Kumanyika
Journal: Annual Review of Public Health (2010)

Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.
Roles of allocortex and centrencephalon in intentionality and consciousness
Authors: Walter J. Freeman
Journal: Behavioral and Brain Sciences (2007)

“Decortication” does not distinguish between removing all cerebral cortex, including three-layered allocortex or just six-layered neocortex. Functional decortication, by spreading depression, reversibly suppresses only neocortex, leaving minimal intentionality. Removal of all forebrain structures except a hypothalamic “island” blocks all intentional behaviors, leaving only tropisms. To what extent do Merker's examples retain allocortex, and how might such residues affect his interpretations?
Autoregulation of Directly Measured Blood Flows in the Superficial and Deep Venous Drainage Areas of the Cat Kidney
Authors: Åge GALSKOV, OLE I. NISSEN
Journal: Circulation Research (1972)

The renal arterial pressure was changed in steps of 25 mm Hg, or it was successively varied between two levels (100 and 150 mm Hg) to obtain four or five stable flow recordings at each level. Statistical calculations indicated that the blood flows in the two drainage areas of the cat kidney were autoregulated with equal effectiveness (whether judged from inflow or outflow rates). The flows at 100 mm Hg were approximately 95% of the flows at 150 mm Hg. To establish whether the accuracy of the method was sufficient to detect a possible nonautoregulated fraction of the arcuate flow similar in magnitude to that traversing the medulla, the flow data were compared with the flows calculated from a simple mathematical model consisting of three homogeneous compartments (outer cortical, inner cortical, and medullary), each with its own pressure-flow relationship. If the flows through all cortical glomeruli are similarly autoregulated, the experimental results are incompatible with a flow through juxtamedullary glomeruli which is proportional to pressure and constitutes 5-;7%, or more, of the total renal blood flow.
Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials
Authors: G. Folprecht, D. Cunningham, P. Ross, B. Glimelius, F. Di Costanzo, J. Wils, W. Scheithauer, P. Rougier, E. Aranda, H. Hecker, C.-H. Köhne
Journal: Annals of Oncology (2004)
MicroRNA-regulated, Systemically Delivered rAAV9: A Step Closer to CNS-restricted Transgene Expression
Authors: Jun Xie, Qing Xie, Hongwei Zhang, Stefan L Ameres, Jui-Hung Hung, Qin Su, Ran He, Xin Mu, Seemin Seher Ahmed, Soyeon Park, Hiroki Kato, Chengjian Li, Christian Mueller, Craig C Mello, Zhiping Weng, Terence R Flotte, Phillip D Zamore, Guangping Gao
Journal: Molecular Therapy (2010)

Recombinant adeno-associated viruses (rAAVs) that can cross the blood-brain-barrier and achieve efficient and stable transvascular gene transfer to the central nervous system (CNS) hold significant promise for treating CNS disorders. However, following intravascular delivery, these vectors also target liver, heart, skeletal muscle, and other tissues, which may cause untoward effects. To circumvent this, we used tissue-specific, endogenous microRNAs (miRNAs) to repress rAAV expression outside the CNS, by engineering perfectly complementary miRNA-binding sites into the rAAV9 genome. This approach allowed simultaneous multi-tissue regulation and CNS-directed stable transgene expression without detectably perturbing the endogenous miRNA pathway. Regulation of rAAV expression by miRNA was primarily via site-specific cleavage of the transgene mRNA, generating specific 5' and 3' mRNA fragments. Our findings promise to facilitate the development of miRNA-regulated rAAV for CNS-targeted gene delivery and other applications.
Fletcher factor deficiency. A diminished rate of Hageman factor activation caused by absence of prekallikrein with abnormalities of coagulation, fibrinolysis, chemotactic activity, and kinin generation.
Authors: A S Weiss, J I Gallin, A P Kaplan
Journal: Journal of Clinical Investigation (1974)

Fletcher factor-deficient plasma is deficient in prekallikrein and therefore generates no bradykinin upon activation with kaolin. It also possesses a diminished rate of kaolin-activable coagulation and fibrinolysis and possesses a defect in kaolin-activable chemotactic activity. These abnormalities are also corrected by reconstitution with purified prekallikrein. Addition of intact activated Hageman factor corrected the coagulation, fibrinolytic, and chemotactic defects and addition of Hageman factor fragments corrected the fibrinolytic defect and partially corrected the chemotactic defect; neither of these corrected the kinin-generating defect. Although the Hageman factor-dependent pathways appear to be initiated by contact activation of Hageman factor, the kallikrein generated activates more Hageman factor; this feedback is necessary for the Hageman factor-dependent pathways to proceed at a normal rate. It is the absence of this feedback in Fletcher factor-deficient plasma that accounts for the diminished rate of activation of Hageman factor and therefore a diminished rate of activation of the coagulation and fibrinolytic pathways. The ability of prekallikrein to correct the coagulation, fibrinolytic, kinin-generating, and chemotactic defects of Fletcher factor-deficient plasma is consistent with the identity of the Fletcher factor and prekallikrein.
Inhibition of Rat Prostate Carcinogenesis by a 5 -Reductase Inhibitor, FK143
Authors: Y. Homma, M. Kaneko, Y. Kondo, K. Kawabe, T. Kakizoe
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Androgen levels in the prostate may influence carcinogenesis in this organ. Inhibitors of the enzyme 5α-reductase block conversion of testosterone to the more active androgen dihydrotestosterone. The use of a 5α-reductase inhibitor, finasteride, in the chemoprevention of prostate cancer is being evaluated in a clinical trial. Purpose: This study was conducted to determine if a 5α-reductase inhibitor, FK143, inhibits the development of prostate cancer in rats. Methods: Male ACI/Seg rats, which spontaneously develop prostate cancer, were randomly assigned at 80 weeks of age to receive one of three diets (n = 35/group) containing 0 (i.e., control group), 20, or 200 ppm FK143. At 140 weeks of age, the animals were killed, and the prostates were removed and examined for histopathologic features in addition to being assayed for androgen concentrations. Two-sided statistical tests were used to calculate all P values. Results: The incidence of prostate carcinoma in the control group was 62.9% (22 of 35 rats); in the group fed the 20 ppm FK143-containing diet, it was 45.7% (16 of 35); and in the group fed the 200 ppm FK143-containing diet, it was 67.6% (23 of 34) (overall, P = .153). The corresponding incidences of macroscopic lesions were 17.1% (six of 35 rats), 0% (none of 35), and 23.5% (eight of 34), respectively (overall, P = .004). The incidence of macroscopic lesions in the prostates of rats in the 20- ppm diet group was significantly lower than that in the control group (P = .029) or that in the 200-ppm diet group (P = .003). Intraprostatic dihydrotestosterone content was significantly lower in rats in the groups fed diets containing 20 or 200 ppm FK143 (mean values: 4.51 and 4.33 pg/mg wet weight of prostate tissue, respectively) than in the control group (6.10 pg/mg) (overall, P<.001); by contrast, testosterone was higher in the 200-ppm diet group (2.09 pg/mg) than in the control group (1.08 pg/mg) or the 20-ppm diet group (1.21 pg/mg) (overall, P<.001). Conclusions: FK143, when fed to rats at 20 or 200 ppm, significantly reduced the level of dihydrotestosterone in their prostate tissue. However, the incidence of macroscopic cancer in the prostate was suppressed in rats consuming the 20 ppm FK143-containing diet but not in those consuming the 200-ppm diet. The lack of dose dependence for the chemopreventive activity of FK143 may be explained by the reciprocal increase of tissue testosterone in the 200-ppm diet group. Implications: The 5α-reductase inhibitor FK143 may, at specific doses, reduce the incidence of spontaneously developing prostate cancer; however, whether these findings in rats will apply to humans remains to be determined.
Trauma Surveillance in Cape Town, South Africa
Authors: Andrew Nicol, Lisa Marie Knowlton, Nadine Schuurman, Richard Matzopoulos, Eiman Zargaran, Jonathan Cinnamon, Vanessa Fawcett, Tracey Taulu, S. Morad Hameed
Journal: JAMA Surgery (2014)

IMPORTANCETrauma is a leading cause of death and disability worldwide.In many low-and middle-income countries, formal trauma surveillance strategies have not yet been widely implemented.OBJECTIVE To formalize injury data collection at Groote Schuur Hospital, the chief academic hospital of the University of Cape Town, a level I trauma center, and one of the largest trauma referral hospitals in the world. DESIGN, SETTING, AND PARTICIPANTSThis was a prospective study of all trauma admissions from October 1, 2010, through September 30, 2011, at Groote Schuur Hospital.A standard admission form was developed with multidisciplinary input and was used for both clinical and data abstraction purposes.Analysis of data was performed in 3 parts: demographics of injury, injury risk by location, and access to and maturity of trauma services.Geographic information science was then used to create satellite imaging of injury "hot spots" and to track referral patterns.Finally, the World Health Organization trauma system maturity index was used to evaluate the current breadth of the trauma system in place. MAIN OUTCOMES AND MEASURESThe demographics of trauma patients, the distribution of injury in a large metropolitan catchment, and the patterns of injury referral and patient movement within the trauma system. RESULTSThe minimum 34-point data set captured relevant demographic, geographic, incident, and clinical data for 9236 patients.Data field completion rates were highly variable.An analysis of demographics of injury (age, sex, and mechanism of injury) was performed.Most violence occurred toward males (71.3%) who were younger than 40 years of age (74.6%).We demonstrated high rates of violent interpersonal injury (71.6% of intentional injury) and motor vehicle injury (18.8% of all injuries).There was a strong association between injury and alcohol use, with alcohol implicated in at least 30.1% of trauma admissions.From a systems standpoint, the data suggest a mature pattern of referral consistent with the presence of an inclusive trauma system. CONCLUSIONS AND RELEVANCEThe implementation of injury surveillance at Groote Schuur Hospital improved insights about injury risk based on demographics and neighborhood as well as access to service based on patterns of referral.This information will guide further development of South Africa's already advanced trauma system.
Body Image Perception Among Men in Three Countries
Authors: Harrison G. Pope, Amanda J. Gruber, Barbara Mangweth, Benjamin Bureau, Christine deCol, Roland Jouvent, James I. Hudson
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors tested the hypothesis that men in modern Western societies would desire to have a much leaner and more muscular body than the body they actually had or perceived themselves to have. METHOD: The height, weight, and body fat of college-aged men in Austria (N=54), France (N=65), and the United States (N=81) were measured. Using the somatomorphic matrix, a computerized test devised by the authors, the men chose the body image that they felt represented 1) their own body, 2) the body they ideally would like to have, 3) the body of an average man of their age, and 4) the male body they believed was preferred by women. The men's actual fat and muscularity was compared with that of the four images chosen. RESULTS: Only slight demographic and physical differences were found among the three groups of men. Modest differences were found between the men's measured fat and the fat of the images chosen. However, measures of muscularity produced large and highly significant differences. In all three countries, men chose a ideal body that was a mean of about 28 lb (13 kg) more muscular than themselves and estimated that women preferred a male body about 30 lb (14 kg) more muscular than themselves. In a pilot study, however, the authors found that actual women preferred an ordinary male body without added muscle. CONCLUSIONS: The wide discrepancy between men's actual muscularity and their body ideals may help explain the apparent rise in disorders such as muscle dysmorphia and anabolic steroid abuse.
Immune responses to JC virus in patients with multiple sclerosis treated with natalizumab: a cross-sectional and longitudinal study
Authors: Samantha Jilek, Emilie Jaquiéry, Hans H Hirsch, Andreas Lysandropoulos, Mathieu Canales, Laurence Guignard, Myriam Schluep, Giuseppe Pantaleo, Renaud A Du Pasquier
Journal: The Lancet Neurology (2010)
Impact of guidance documents on translational large animal studies of cartilage repair
Authors: Christian G. Pfeifer, Matthew B. Fisher, James L. Carey, Robert L. Mauck
Journal: Science Translational Medicine (2015)

Promising therapies for cartilage repair are translated through large animal models toward human application. To guide this work, regulatory agencies publish recommendations ("guidance documents") to direct pivotal large animal studies. These are meant to aid in study design, outline metrics for judging efficacy, and facilitate comparisons between studies. To determine the penetrance of these documents in the field, we synthesized the recommendations of the American Society for Testing and Materials, U.S. Food and Drug Administration, and European Medicines Agency into a scoring system and performed a systematic review of the past 20 years of preclinical cartilage repair studies. Our hypothesis was that the guidance documents would have a significant impact on how large animal cartilage repair studies were performed. A total of 114 publications meeting our inclusion criteria were reviewed for adherence to 24 categories extracted from the guidance documents, including 11 related to study design and description and 13 related to study outcomes. Overall, a weak positive trend was observed over time (P = 0.004, R(2) = 0.07, slope = 0.63%/year), with overall adherence (the sum of study descriptors and outcomes) ranging from 32 ± 16% to 58 ± 14% in any individual year. There was no impact of the publication of the guidance documents on adherence (P = 0.264 to 0.50). Given that improved adherence would expedite translation, we discuss the reasons for poor adherence and outline approaches to increase and promote their more widespread adoption.