tbuckley/cabot-search huggingface dataset:
Dealing With Dietary Measurement Error in Nutritional Cohort Studies
Authors: Laurence S. Freedman, Arthur Schatzkin, Douglas Midthune, Victor Kipnis
Journal: JNCI Journal of the National Cancer Institute (2011)

Dietary measurement error creates serious challenges to reliably discovering new diet–disease associations in nutritional cohort studies. Such error causes substantial underestimation of relative risks and reduction of statistical power for detecting associations. On the basis of data from the Observing Protein and Energy Nutrition Study, we recommend the following approaches to deal with these problems. Regarding data analysis of cohort studies using food-frequency questionnaires, we recommend 1) using energy adjustment for relative risk estimation; 2) reporting estimates adjusted for measurement error along with the usual relative risk estimates, whenever possible (this requires data from a relevant, preferably internal, validation study in which participants report intakes using both the main instrument and a more detailed reference instrument such as a 24-hour recall or multiple-day food record); 3) performing statistical adjustment of relative risks, based on such validation data, if they exist, using univariate (only for energy-adjusted intakes such as densities or residuals) or multivariate regression calibration. We note that whereas unadjusted relative risk estimates are biased toward the null value, statistical significance tests of unadjusted relative risk estimates are approximately valid. Regarding study design, we recommend increasing the sample size to remedy loss of power; however, it is important to understand that this will often be an incomplete solution because the attenuated signal may be too small to distinguish from unmeasured confounding in the model relating disease to reported intake. Future work should be devoted to alleviating the problem of signal attenuation, possibly through the use of improved self-report instruments or by combining dietary biomarkers with self-report instruments.
Evaluation of the immunogenicity of aldhhigh human head and neck squamous cell carcinoma cancer stem cells in vitro
Authors: Qiao Li, Mark Prince
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Using mouse models we reported that dendritic cells (DC) pulsed with cancer stem cells (CSC) enriched by virtue of their expression of the CSC marker aldehyde dehydrogenase (ALDH) significantly reduced development of pulmonary metastases and prolonged survival. In this recent
Effect of Testosterone Replacement Therapy on Prostate Tissue in Men With Late-Onset Hypogonadism
Authors: Leonard S. Marks, Norman A. Mazer, Elahe Mostaghel, David L. Hess, Frederick J. Dorey, Jonathan I. Epstein, Robert W. Veltri, Danil V. Makarov, Alan W. Partin, David G. Bostwick, Maria Luz Macairan, Peter S. Nelson
Journal: JAMA (2006)

Prostate safety is a primary concern when aging men receive testosterone replacement therapy (TRT), but little information is available regarding the effects of TRT on prostate tissue in men.To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels.Randomized, double-blind, placebo-controlled trial of 44 men, aged 44 to 78 years, with screening serum testosterone levels lower than 300 ng/dL (<10.4 nmol/L) and related symptoms, conducted at a US community-based research center between February 2003 and November 2004.Participants were randomly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months.The primary outcome measure was the 6-month change in prostate tissue androgen levels (testosterone and dihydrotestosterone). Secondary outcome measures included 6-month changes in prostate-related clinical features, histology, biomarkers, and epithelial cell gene expression.Of the 44 men randomized, 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per-protocol analysis (TRT, n = 21; placebo, n = 19). Testosterone replacement therapy increased serum testosterone levels to the mid-normal range (median at baseline, 282 ng/dL [9.8 nmol/L]; median at 6 months, 640 ng/dL [22.2 nmol/L]) with no significant change in serum testosterone levels in matched, placebo-treated men. However, median prostate tissue levels of testosterone (0.91 ng/g) and dihydrotestosterone (6.79 ng/g) did not change significantly in the TRT group. No treatment-related change was observed in prostate histology, tissue biomarkers (androgen receptor, Ki-67, CD34), gene expression (including AR, PSA, PAP2A, VEGF, NXK3, CLU [Clusterin]), or cancer incidence or severity. Treatment-related changes in prostate volume, serum prostate-specific antigen, voiding symptoms, and urinary flow were minor.These preliminary data suggest that in aging men with late-onset hypogonadism, 6 months of TRT normalizes serum androgen levels but appears to have little effect on prostate tissue androgen levels and cellular functions. Establishment of prostate safety for large populations of older men undergoing longer duration of TRT requires further study. Trial Registration clinicaltrials.gov Identifier: NCT00161304.
Evolutionary social science beyond culture
Authors: Harold Kincaid
Journal: Behavioral and Brain Sciences (2006)

Mesoudi et al.'s case can be improved by expanding to compelling selectionist explanations elsewhere in the social sciences and by seeing that natural selection is an instance of general selectionist process. Obstacles include the common use of extreme idealizations and optimality evidence, the copresence of nonselectionist social processes, and the fact that selectionist explanations often presuppose other kinds of social explanations.
The association between the metabolic syndrome and alanine amino transferase is mediated by insulin resistance via related metabolic intermediates (the Cohort on Diabetes and Atherosclerosis Maastricht [CODAM] study)
Authors: Marjon Jacobs, Marleen M.J. van Greevenbroek, Carla J.H. van der Kallen, Isabel Ferreira, Edith J.M. Feskens, Eugene H.J.M. Jansen, Casper G. Schalkwijk, Coen Stehouwer
Journal: Metabolism (2010)
Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: A phase II study
Authors: A.A. Brandes, M. Ermani, U. Basso, P. Amistà, F. Berti, R. Scienza, A. Rotilio, G. Pinna, M. Gardiman, S. Monfardini
Journal: Annals of Oncology (2001)
Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults
Authors: S. Sistonen, P. Malmberg, K. Malmstrom, T. Haahtela, S. Sarna, R. J. Rintala, M. P. Pakarinen
Journal: European Respiratory Journal (2010)

Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947–1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22–56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p&lt;0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatroy defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3–8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0–8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.
Paired Activating and Inhibitory Immunoglobulin-like Receptors, MAIR-I and MAIR-II, Regulate Mast Cell and Macrophage Activation
Authors: Katsumi Yotsumoto, Yasushi Okoshi, Kazuko Shibuya, Satoshi Yamazaki, Satoko Tahara-Hanaoka, Shin-ichiro Honda, Mitsujiro Osawa, Asato Kuroiwa, Yoichi Matsuda, Daniel G. Tenen, Atsushi Iwama, Hiromitsu Nakauchi, Akira Shibuya
Journal: The Journal of Experimental Medicine (2003)

Immune responses are regulated by opposing positive and negative signals triggered by the interaction of activating and inhibitory cell surface receptors with their ligands. Here, we describe novel paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptor (MAIR) I and MAIR-II, whose extracellular domains are highly conserved by each other. MAIR-I, expressed on the majority of myeloid cells, including macrophages, granulocytes, mast cells, and dendritic cells, contains the tyrosine-based sorting motif and the immunoreceptor tyrosine-based inhibitory motif-like sequences in the cytoplasmic domain and mediates endocytosis of the receptor and inhibition of IgE-mediated degranulation from mast cells. On the other hand, MAIR-II, expressed on subsets of peritoneal macrophages and B cells, associates with the immunoreceptor tyrosine-based activation motif-bearing adaptor DAP12 and stimulates proinflammatory cytokines and chemokine secretions from macrophages. Thus, MAIR-I and MAIR-II play important regulatory roles in cell signaling and immune responses.
Resveratrol Suppresses Growth of Human Ovarian Cancer Cells in Culture and in a Murine Xenograft Model: Eukaryotic Elongation Factor 1A2 as a Potential Target
Authors: Mee-Hyun Lee, Bu Young Choi, Joydeb Kumar Kundu, Young Kee Shin, Hye-Kyung Na, Young-Joon Surh
Journal: Cancer Research (2009)

Abstract The eukaryotic elongation factor 1A2 (eEF1A2) is known to retain oncogenic potential and is recognized as a novel target for cancer prevention and therapy. Resveratrol (trans-3,4′,5-trihydroxystilbene), a phytoalexin present in grapes, has been reported to possess chemopreventive and chemotherapeutic activities. In the present study, we examined the growth-inhibitory effects of resveratrol in human ovarian cancer PA-1 cells, considering eEF1A2 as a potential molecular target. Pretreatment with resveratrol attenuated proliferation of serum-starved PA-1 cells stimulated with insulin or serum. Resveratrol also activated caspase-9, -7, and -3 and induced apoptosis in PA-1 cells in the presence of insulin or serum. Insulin or serum stimulation of PA-1 cells resulted in the marked induction of eEF1A2, which was suppressed by pretreatment with resveratrol. Moreover, resveratrol inhibited insulin- or serum-induced soft-agar colony formation in eEF1A2-transfected NIH3T3 cells. An antibody array directed to assess the phosphorylation of protein kinases revealed that treatment with insulin or serum induced the phosphorylation of Akt in PA-1 cells. Pharmacologic inhibition of Akt with LY294002 abrogated insulin- or serum-induced eEF1A2 expression and increased the caspase-3 activity. In another experiment, i.p. administration of resveratrol retarded the growth of PA-1 cell xenograft and the expression of eEF1A2 in athymic nude mice in association with decreased bromodeoxyuridine positivity, reduced expression of proliferating cell nuclear antigen, increased the terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and caspase-3 staining, and diminished CD31 positivity. Taken together, eEF1A2 may be considered as a potential molecular target for the antiproliferative effects of resveratrol in PA-1 ovarian cancer cells. [Cancer Res 2009;69(18):7449–58]
Asthma, COPD and bronchitis are just components of airway disease
Authors: F. E. Hargreave, K. Parameswaran
Journal: European Respiratory Journal (2006)

Diseases of the airways of the lungs are common and include asthma, chronic obstructive pulmonary disease (COPD) and bronchitis, as well as emphysema and bronchiectasis. Their diagnosis is often inaccurate because appropriate measurements are not made 1–3 and the definition of airway disease is still imprecise. For example, the Global Initiative for Asthma (GINA) definition of asthma describes components but fails to give a primary definition which distinguishes the disease from others 4. The Canadian definition of COPD includes partly reversible airflow limitation, which is what many would define as asthma 5. Therefore, it seems appropriate to reconsider how we diagnose and define airway disease; this is important in order to optimise treatment.

The components (characteristics, features, etc. ) of airway disease include symptoms, variable airflow limitation, airway hyperresponsiveness, chronic airflow limitation and airway inflammation, as well as emphysema and bronchiectasis (fig. 1⇓). They can exist in various combinations. Airway inflammation is central to all other components. It is a cause of symptoms, variable airflow limitation through release of bronchoconstrictor mediators, and chronic airflow limitation through remodelling with structural changes. It also increases airway responsiveness. These components correlate poorly with one another 6–9. The best correlation is between the diurnal variation of peak expiratory flow (PEF) and airway responsiveness 10, which is not surprising since the latter is an important determinant of the former. Symptoms of chest tightness, wheezing, dyspnoea, cough and sputum are all nonspecific since they can result from each of the other components, as well as other respiratory and nonrespiratory conditions. Hence, measurements are needed to be certain as to what the symptoms are associated with.



Fig. 1— 
Relationships between components of airway diseases. Airway inflammation influences all other components, including emphysema and bronchiectasis, which are not shown. Airway hyperresponsiveness is an …
Magnetic Resonance Imaging Screening of the Contralateral Breast in Women With Newly Diagnosed Breast Cancer: Systematic Review and Meta-Analysis of Incremental Cancer Detection and Impact on Surgical Management
Authors: Meagan Elizabeth Brennan, Nehmat Houssami, Sarah Lord, Petra Macaskill, Les Irwig, J. Michael Dixon, Ruth M.L. Warren, Stefano Ciatto
Journal: Journal of Clinical Oncology (2009)

Preoperative magnetic resonance imaging (MRI) is increasingly used for staging women with breast cancer, including screening for occult contralateral cancer. This article is a review and meta-analysis of studies reporting contralateral MRI in women with newly diagnosed invasive breast cancer.We systematically reviewed the evidence on contralateral MRI, calculating pooled estimates for positive predictive value (PPV), true-positive:false-positive ratio (TP:FP), and incremental cancer detection rate (ICDR) over conventional imaging. Random effects logistic regression examined whether estimates were associated with study quality or clinical variables.Twenty-two studies reported contralateral malignancies detected only by MRI in 131 of 3,253 women. Summary estimates were as follows: MRI-detected suspicious findings (TP plus FP), 9.3% (95% CI, 5.8% to 14.7%); ICDR, 4.1% (95% CI, 2.7% to 6.0%), PPV, 47.9% (95% CI, 31.8% to 64.6%); TP:FP ratio, 0.92 (95% CI, 0.47 to 1.82). PPV was associated with the number of test positives and baseline imaging. Few studies included consecutive women, and few ascertained outcomes in all subjects. Where reported, 35.1% of MRI-detected cancers were ductal carcinoma in situ (mean size = 6.9 mm), 64.9% were invasive cancers (mean size = 9.3 mm), and the majority were stage pTis or pT1 and node negative. Effect on treatment was inconsistently reported, but many women underwent contralateral mastectomy.MRI detects contralateral lesions in a substantial proportion of women, but does not reliably distinguish benign from malignant findings. Relatively high ICDR may be due to selection bias and/or overdetection. Women must be informed of the uncertain benefit and potential harm, including additional investigations and surgery.
Effect of ethanol on ketone metabolism
Authors: André Lefèvre, Howard Adler, Charles S. Lieber
Journal: Journal of Clinical Investigation (1970)

Ketonuria has been observed in alcoholics. To study the mechanism of this effect, healthy, volunteers were given adequate diets (36% of calories as lipid and 15% as protein) for 18 days, with isocaloric replacement of carbohydrate (46% of calories) by either ethanol or additional fat. The latter resulted in a high fat diet, with 82% of calories as lipid. After about 1 wk of alcohol, massive and persistent ketonuria developed. Compared with the control period, there was a 30-fold increase in fasting blood acetoacetate and β-hydroxybutyrate (P < 0.001). With the high fat diet, acetoacetate and β-hydroxybutyrate increased 8- to 10-fold (P < 0.001). In the postprandial state, ethanol also induced hyperketonemia, but less markedly than when ethanol followed an overnight fast. With low fat diets (5% of calories), alcohol (46% of total calories) did not induce ketonuria or hyperketonemia, suggesting that a combination of alcohol and dietary fat is necessary. The addition of alcohol to rat liver slices did not affect ketogenesis. In rats pretreated with alcohol for 3 days, however, ketonemia developed, hepatic glycogen was decreased, and liver slices (incubated with palmitate-14C and glucose) had a significant increase in acetoacetate production, when compared to carbohydrate pretreated controls. Alcohol pretreatment or addition of alcohol in vitro had no effect on acetoacetate utilization by rat diaphragms, and decreased only slightly the conversion of β-hydroxybutyrate-14C to 14CO2. Thus, the hyperketonemia and ketonuria observed after alcohol consumption cannot be attributed to an immediate effect of alcohol, but is the consequence of a delayed change in intermediary metabolism characterized by increased hepatic ketone production from fatty acids, possibly linked to ethanol-induced glycogen depletion and depression of citric acid cycle activity.
Perlecan is critical for heart stability
Authors: Philipp Sasse, Daniela Malan, Michaela Fleischmann, Wilhelm Roell, Erika Gustafsson, Toktam Bostani, Yun Fan, Thomas Kolbe, Martin Breitbach, Klaus Addicks, Armin Welz, Gottfried Brem, Jürgen Hescheler, Attila Aszodi, Mercedes Costell, Wilhelm Bloch, Bernd K. Fleischmann
Journal: Cardiovascular Research (2008)

Perlecan is a heparansulfate proteoglycan found in basement membranes, cartilage, and several mesenchymal tissues that form during development, tumour growth, and tissue repair. Loss-of-function mutations in the perlecan gene in mice are associated with embryonic lethality caused primarily by cardiac abnormalities probably due to hemopericards. The aim of the present study was to investigate the mechanism underlying the early embryonic lethality and the pathophysiological relevance of perlecan for heart function. Perlecan-deficient murine embryonic stem cells were used to investigate the myofibrillar network and the electrophysiological properties of single cardiomyocytes. The mechanical stability of the developing perlecan-deficient mouse hearts was analysed by microinjecting fluorescent-labelled dextran. Maturation and formation of basement membranes and cell–cell contacts were investigated by electron microscopy, immunohistochemistry, and western blotting. Sarcomere formation and cellular functional properties were unaffected in perlecan-deficient cardiomyocytes. However, the intraventricular dye injection experiments revealed mechanical instability of the early embryonic mouse heart muscle wall before embryonic day 10.5 (E10.5). Accordingly, perlecan-null embryonic hearts contained lower amounts of the critical basement membrane components, collagen IV and laminins. Furthermore, basement membranes were absent in perlecan-null cardiomoycytes whereas adherens junctions formed and matured around E9.5. Infarcted hearts from perlecan heterozygous mice displayed reduced heart function when compared with wild-type hearts. We propose that perlecan plays an important role in maintaining the integrity during cardiac development and is important for heart function in the adult heart after injury.
Relationship between Kidney Size, Renal Injury, and Renal Impairment Induced by Shock Wave Lithotripsy
Authors: LYNN R. WILLIS, ANDREW P. EVAN, BRET A. CONNORS, PHIL BLOMGREN, NAOMI S. FINEBERG, JAMES E. LINGEMAN
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The relationship between kidney size and impaired renal function induced by shock-wave lithotripsy (SWL) was examined in 6- and 10-wk-old anesthetized pigs. Each pig received 2000 shock waves, 24 kV, or sham SWL to the lower pole calyx of one kidney. Bilateral GFR, renal plasma flow (RPF), and para-aminohippurate extraction was measured 1 h before and 1 and 4 h after SWL. The kidneys were then removed for morphometric analysis. Mean kidney weights were 66.1 ± 2.7 g ( n = 9) and 103.1 ± 3.3 g ( n = 8) in the SWL groups, and 60.1 ± 2.6 g ( n = 9) and 82.3 ± 4.0 g ( n = 9) in the sham-SWL groups. SWL-induced lesions occupied a significantly greater volume of the small kidneys (6.1 ± 1.7 vol % versus 1.5 ± 0.2 vol % in the large kidneys). RPF was significantly reduced by SWL in small and large kidneys, but to a significantly greater extent in small kidneys. RPF was also significantly reduced in the contralateral kidneys of both groups, but only at 1 h after SWL. SWL significantly reduced GFR to similar degrees in both kidneys of both groups, regardless of kidney size. Para-aminohippurate extraction was likewise reduced to similar degrees in both groups, but this effect was evident only in the SWL-treated kidneys, and only in the pole to which the shock waves had been applied. The injury induced by SWL affected a larger fraction of small kidneys than large ones, and the renal vasoconstriction induced by SWL was greatest in small kidneys.
Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers
Authors: Xinyuan Li, Pu Fang, Jietang Mai, Eric T Choi, Hong Wang, Xiao-feng Yang
Journal: Journal of Hematology & Oncology (2013)

Abstract There are multiple sources of reactive oxygen species (ROS) in the cell. As a major site of ROS production, mitochondria have drawn considerable interest because it was recently discovered that mitochondrial ROS (mtROS) directly stimulate the production of proinflammatory cytokines and pathological conditions as diverse as malignancies, autoimmune diseases, and cardiovascular diseases all share common phenotype of increased mtROS production above basal levels. Several excellent reviews on this topic have been published, but ever-changing new discoveries mandated a more up-to-date and comprehensive review on this topic. Therefore, we update recent understanding of how mitochondria generate and regulate the production of mtROS and the function of mtROS both in physiological and pathological conditions. In addition, we describe newly developed methods to probe or scavenge mtROS and compare these methods in detail. Thorough understanding of this topic and the application of mtROS-targeting drugs in the research is significant towards development of better therapies to combat inflammatory diseases and inflammatory malignancies.