tbuckley/cabot-search huggingface dataset:
The Serotonin System and Spiritual Experiences
Authors: Jacqueline Borg, Bengt Andrée, Henrik Soderstrom, Lars Farde
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The serotonin system has long been of interest in biological models of human personality. The purpose of this positron emission tomography (PET) study was to search for relationships between serotonin 5-HT1A receptor density and personality traits. METHOD: Fifteen normal male subjects, ages 20–45 years, were examined with PET and the radioligand [11C]WAY100635. Personality traits were assessed with the Swedish version of the Temperament and Character Inventory self-report questionnaire. Binding potential, an index for the density of available 5-HT1A receptors, was calculated for the dorsal raphe nuclei, the hippocampal formation, and the neocortex. For each region, correlation coefficients between 5-HT1A receptor binding potential and Temperament and Character Inventory personality dimensions were calculated and analyzed in two-tailed tests for significance. RESULTS: The authors found that the binding potential correlated inversely with scores for self-transcendence, a personality trait covering religious behavior and attitudes. No correlations were found for any of the other six Temperament and Character Inventory dimensions. The self-transcendence dimension consists of three distinct subscales, and further analysis showed that the subscale for spiritual acceptance correlated significantly with binding potential but not with the other two subscales. CONCLUSIONS: This finding in normal male subjects indicated that the serotonin system may serve as a biological basis for spiritual experiences. The authors speculated that the several-fold variability in 5-HT1A receptor density may explain why people vary greatly in spiritual zeal.
Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma
Authors: Danny CW Yu, Jonathan P Bury, James Tiernan, Jennifer S Waby, Carolyn A Staton, Bernard M Corfe
Journal: Molecular Cancer (2011)

Abstract Background Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo . Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate). Additionally we sought to assess whether there is a field effect around adenomas. Methodology Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field) of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA), a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels. Result NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid), but expression was lower and not related to SCFA concentration at the field. Likewise CgA + cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue shows dissociation of the co-regulation of NRP-1 and EEC. Conclusion NRP-1 is inversely associated with levels of butyrate and other SCFA in vivo and is expressed in a subset of CgA expressing cells. EEC number is related to butyrate level in the same way.
Activation of Cancer-Specific Gene Expression by the Survivin Promoter
Authors: R. Bao
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Survivin, a member of the IAP (inhibitor of apoptosis) gene family, appears to be overexpressed in common cancers but not in corresponding normal adult tissues. To investigate whether the survivin promoter controls cancer cell–specific gene expression, we determined whether the survivin gene promoter could regulate reporter gene expression in cancer cell lines and xenografts. Methods: Survivin protein levels were determined in human and murine cancer cell lines and in normal tissues of adult C57BL/6 mice by Western blot analysis. A reporter construct in which a portion of the survivin gene promoter was used to drive transcription of a human secreted alkaline phosphatase (SEAP) gene was transiently transfected into cancer cells, and promoter activity was extrapolated from SEAP activity. A2780 human ovarian cancer cells were transfected with this construct, and stable transfectants were injected into the intrabursal ovarian space of immunodeficient mice. Tumor growth was monitored, and plasma SEAP levels were used as a measure of survivin promoter activity in vivo. Results: Survivin protein was detected in all cancer cell lines examined but not in most normal adult mouse tissues. After transfection, the survivin promoter was more active in all cancer cell lines than in normal ovarian surface epithelial cells or mouse 3T3 cells. After 0.8 × 106 stable transfectant cells were injected into the intrabursal cavity of mouse ovaries, plasma SEAP activity was detected within 24 hours, and the activity increased with time and tumor growth. Conclusion: Transfection experiments indicate that survivin protein expression in cancer tissue appears to be regulated, at least in part, transcriptionally. Thus, the survivin promoter may be useful in controlling gene expression in cancer cells.
No proof that lung transplantation improves survival in cystic fibrosis
Authors: Iain Drummond
Journal: Thorax (2008)

Lung transplantation is a common procedure with significant risks undertaken in children with cystic fibrosis. This retrospective study investigates the effect of lung transplantation on survival.

Five hundred and fourteen of 602 children (85%) aged <18 years with cystic fibrosis placed on the lung transplantation waiting list in the USA between 1992 and 2002 were …
Research governance: ethical issues
Authors: Anne Slowther, Petra Boynton, Sara Shaw
Journal: Journal of the Royal Society of Medicine (2006)

Healthcare research is haunted by a history of unethical studies in which profound harm was caused to vulnerable individuals. Official systems for gaining ethical approval for research, designed to prevent a repetition of these shameful examples, can prove bureaucratic and inflexible in practice. The core ethical principles of respect for autonomy, prevention of harm, promotion of benefit, and justice (which form the basis of professional codes of research conduct) must be applied flexibly to take account of contextual, methodological, personal and practical considerations. Ensuring that the design and conduct of all research is ethically sound is the responsibility of all involved–-including researchers, research institutions, ethics review committees and regulatory bodies.
A Case-Crossover Analysis of Out-of-Hospital Cardiac Arrest and Air Pollution
Authors: Katherine B. Ensor, Loren H. Raun, David Persse
Journal: Circulation (2013)

Background— Evidence of an association between the exposure to air pollution and overall cardiovascular morbidity and mortality is increasingly found in the literature. However, results from studies of the association between acute air pollution exposure and risk of out-of-hospital cardiac arrest (OHCA) are inconsistent for fine particulate matter, and, although pathophysiological evidence indicates a plausible link between OHCA and ozone, none has been reported. Approximately 300 000 persons in the United States experience an OHCA each year, of which &gt;90% die. Understanding the association provides important information to protect public health. Methods and Results— The association between OHCA and air pollution concentrations hours and days before onset was assessed by using a time-stratified case-crossover design using 11 677 emergency medical service–logged OHCA events between 2004 and 2011 in Houston, Texas. Air pollution concentrations were obtained from an extensive area monitor network. An average increase of 6 µg/m 3 in fine particulate matter 2 days before onset was associated with an increased risk of OHCA (1.046; 95% confidence interval, 1.012–1.082). A 20-ppb ozone increase for the 8-hour average daily maximum was associated with an increased risk of OHCA on the day of the event (1.039; 95% confidence interval, 1.005–1.073). Each 20-ppb increase in ozone in the previous 1 to 3 hours was associated with an increased risk of OHCA (1.044; 95% confidence interval, 1.004–1.085). Relative risk estimates were higher for men, blacks, or those aged &gt;65 years. Conclusions— The findings confirm the link between OHCA and fine particulate matter and introduce evidence of a similar link with ozone.
International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?
Authors: Lorenzo D Botto, Alessandra Lisi, Elisabeth Robert-Gnansia, J David Erickson, Stein Emil Vollset, Pierpaolo Mastroiacovo, Beverley Botting, Guido Cocchi, Catherine de Vigan, Hermien de Walle, Maria Feijoo, Lorentz M Irgens, Bob McDonnell, Paul Merlob, Annukka Ritvanen, Gioacchino Scarano, Csaba Siffel, Julia Metneki, Claude Stoll, Richard Smithells, Janine Goujard
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. <b>Design</b> Retrospective cohort study of births monitored by birth defect registries. <b>Setting</b> 13 birth defects registries monitoring rates of neural tube defects from 1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales, Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were ascertained among liveborn infants, stillbirths, and pregnancy terminations (where legal). Policies and recommendations were ascertained by interview and literature review. <b>Main outcome measures</b> Incidences and trends in rates of neural tube defects before and after 1992 (the year of the first recommendations) and before and after the year of local recommendations (when applicable). <b>Results</b> The issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of neural tube defects. <b>Conclusions</b> Recommendations alone did not seem to influence trends in neural tube defects up to six years after the confirmation of the effectiveness of folic acid in clinical trials. New cases of neural tube defects preventable by folic acid continue to accumulate. A reasonable strategy would be to quickly integrate food fortification with fuller implementation of recommendations on supplements.
Neuropeptidergic Control of Sleep and Wakefulness
Authors: Constance Richter, Ian G. Woods, Alexander F. Schier
Journal: Annual Review of Neuroscience (2014)

Sleep and wake are fundamental behavioral states whose molecular regulation remains mysterious. Brain states and body functions change dramatically between sleep and wake, are regulated by circadian and homeostatic processes, and depend on the nutritional and emotional condition of the animal. Sleep-wake transitions require the coordination of several brain regions and engage multiple neurochemical systems, including neuropeptides. Neuropeptides serve two main functions in sleep-wake regulation. First, they represent physiological states such as energy level or stress in response to environmental and internal stimuli. Second, neuropeptides excite or inhibit their target neurons to induce, stabilize, or switch between sleep-wake states. Thus, neuropeptides integrate physiological subsystems such as circadian time, previous neuron usage, energy homeostasis, and stress and growth status to generate appropriate sleep-wake behaviors. We review the roles of more than 20 neuropeptides in sleep and wake to lay the foundation for future studies uncovering the mechanisms that underlie the initiation, maintenance, and exit of sleep and wake states.
Global patterns of cardia and non-cardia gastric cancer incidence in 2012
Authors: A Colquhoun, M Arnold, J Ferlay, K J Goodman, D Forman, I Soerjomataram
Journal: Gut (2015)

Objective Globally, gastric cancer incidence shows remarkable international variation and demonstrates distinct characteristics by the two major topographical subsites, cardia (CGC) and non-cardia (NCGC). Because global incidence estimates by subsite are lacking, we aimed to describe the worldwide incidence patterns of CGC and NCGC separately. Design Using Cancer Incidence in Five Continents Volume X (CI5X), we ascertained the proportions of CGC and NCGC by country, sex and age group (<65 and ≥65 years). These derived proportions were applied to GLOBOCAN 2012 data to estimate country-specific age-standardised CGC and NCGC incidence rates (ASR). Regional proportions were used to estimate rates for countries not included in CI5X. Results According to our estimates, in 2012, there were 260 000 cases of CGC (ASR 3.3 per 100 000) and 691 000 cases of NCGC (ASR 8.8) worldwide. The highest regional rates of both gastric cancer subsites were in Eastern/Southeastern Asia (in men, ASRs: 8.7 and 21.7 for CGC and NCGC, respectively). In most countries NCGC occurred more frequently than CGC with an average ratio of 2:1; however, in some populations where NCGC incidence rates were lower than the global average, CGC rates were similar or higher than NCGC rates. Men had higher rates than women for both subsites but particularly for CGC (male-to-female ratio 3:1). Conclusions This study has, for the first time, quantified global incidence patterns of CGC and NCGC providing new insights into the global burden of these cancers. Country-specific estimates are provided; however, these should be interpreted with caution. This work will support future investigations across populations.
Design and Validation of a Population-Based Definition of the Metabolic Syndrome
Authors: Carlos A. Aguilar-Salinas, Rosalba Rojas, Clicerio Gonzalez-Villalpando, Francisco J. Gómez-Pérez, Roopa Mehta, Gustavo Olaiz, Juan A. Rull, David R. Cox
Journal: Diabetes Care (2006)

The National Cholesterol Education Program (NCEP) definition of the metabolic syndrome was modified to be described as a continuous variable and adapted to the characteristics of a Hispanic population.Age/sex population percentiles for every component of the NCEP criteria were included in this approach using population-based data from a Mexican nationwide survey (2,158 subjects). One point was given per decile for every component. The total number of points accumulated was used to classify subjects. The predictive power for incident diabetes was evaluated using the 7-year follow-up results of the Mexico City Diabetes Study.Our population-based method had a significantly better prognostic power compared with the original and the updated NCEP definitions (area under the receiver operating characteristic curve 0.746 vs. 0.697 and 0.723, respectively, P < 0.05). Using individuals with </=1 component of the NCEP definition as reference, the odds ratio was greater in the upper quartile of the points scale (>/=39 points) (12.71 [95% CI 5.67-28.49]) compared with that calculated for the original (9.52 [4.69-19.31]) and the updated (11.14 [5.33-23.30]) NCEP criteria. The major advantage of our approach is the detection of subjects at the extremes of the range of diabetes risk and the ability to estimate this risk as a continuum.Our method adapts the NCEP criteria to the characteristics of a Hispanic population. It improves the predictive power of the NCEP criteria for future diabetes.
Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype
Authors: Stephen C. Mack, Sameer Agnihotri, Kelsey C. Bertrand, Xin Wang, David J. Shih, Hendrik Witt, Nadia Hill, Kory Zayne, Mark Barszczyk, Vijay Ramaswamy, Marc Remke, Yuan Thompson, Marina Ryzhova, Luca Massimi, Wieslawa Grajkowska, Boleslaw Lach, Nalin Gupta, William A. Weiss, Abhijit Guha, Cynthia Hawkins, Sidney Croul, James T. Rutka, Stefan M. Pfister, Andrey Korshunov, Melike Pekmezci, Tarik Tihan, Joanna J. Philips, Nada Jabado, Gelareh Zadeh, Michael D. Taylor
Journal: Clinical Cancer Research (2015)

Myxopapillary ependymoma (MPE) is a distinct histologic variant of ependymoma arising commonly in the spinal cord. Despite an overall favorable prognosis, distant metastases, subarachnoid dissemination, and late recurrences have been reported. Currently, the only effective treatment for MPE is gross-total resection. We characterized the genomic and transcriptional landscape of spinal ependymomas in an effort to delineate the genetic basis of this disease and identify new leads for therapy.Gene expression profiling was performed on 35 spinal ependymomas, and copy number profiling was done on an overlapping cohort of 46 spinal ependymomas. Functional validation experiments were performed on tumor lysates consisting of assays measuring pyruvate kinase M activity (PKM), hexokinase activity (HK), and lactate production.At a gene expression level, we demonstrate that spinal grade II and MPE are molecularly and biologically distinct. These are supported by specific copy number alterations occurring in each histologic variant. Pathway analysis revealed that MPE are characterized by increased cellular metabolism, associated with upregulation of HIF1α. These findings were validated by Western blot analysis demonstrating increased protein expression of HIF1α, HK2, PDK1, and phosphorylation of PDHE1A. Functional assays were performed on MPE lysates, which demonstrated decreased PKM activity, increased HK activity, and elevated lactate production.Our findings suggest that MPE may be driven by a Warburg metabolic phenotype. The key enzymes promoting the Warburg phenotype: HK2, PKM2, and PDK are targetable by small-molecule inhibitors/activators, and should be considered for evaluation in future clinical trials for MPE.
LG-05 * PEDIATRIC GRADE II GLIOMA MOLECULAR SCREENING IN ADOLESCENTS AND YOUNG ADULTS
Authors: I. Ollivier, C. Lasthaus, M. Litzler, D. Guenot, N. Entz-Werle
Journal: Neuro-Oncology (2015)

The grade II gliomas are rare and represent 10% of all gliomas in adult and pediatric populations. Those gliomas are mostly represented by a heterogeneous group of oligodendrogliomas, oligoastrocytomas and diffuse astrocytomas. As in rare tumors, the molecular definition is difficult to establish. Furthermore, those tumors are covering a large range of age from adolescent to young adults. Recent advances in young adult grade II gliomas showed a predominance of ATRX loss expression, 1p/19q codeletion and IDH1/2 mutations, whereas in pediatric setting FGFR1, MYBL1 and BRAF were frequently involved. Then, the major question was why the tumors in patients less than 18 years and in young adults were so different molecularly. Therefore, in a cohort of 37 grade II gliomas (7 pediatric patients less than 18 years and 30 adults), a molecular screening based on both pediatric and adult molecular abnomalities was performed. ATRX, 1p/19q codeletion, IDH1/2, FGFR1, MYBL1 and BRAF status was analyzed. This population had a pattern mixing the molecular and histological data previously described but without any age-dependent dichotomy. Some of the pediatric grade II were presenting IDH1 mutation with ATRX loss, whereas few young adults had BRAF mutations. These results suggest that a larger cohort should be closely analyzed to confirm these preliminary data which considered the grade II glioma in a larger group of age than previously.
Association of S100A4 and osteopontin with specific prognostic factors and survival of patients with minimally invasive breast cancer.
Authors: Suzete de Silva Rudland, Lee Martin, Chandeene Roshanlall, John Winstanley, Samuel Leinster, Angela Platt-Higgins, Joe Carroll, Christopher West, Roger Barraclough, Philip Rudland
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: S100A4 and the estrogen-inducible osteopontin are alone capable of inducing angiogenesis and metastasis in rodent models for breast cancer. The present study assesses the relationship of S100A4 and osteopontin with vessel density and estrogen receptor alpha (ERalpha) in primary tumors and with survival of patients to ascertain their involvement in metastatic breast cancer. EXPERIMENTAL DESIGN: Primary tumors from 312 patients treated for minimally invasive human breast cancer were immunocytochemically stained and then assessed for the significance of their association with each other using Fisher's exact test or with patient survival over 18 years of follow-up using Kaplan-Meier plots and Wilcoxon-Gehan statistics. RESULTS: Antibodies to S100A4 significantly stained endothelial cells of vessels adjacent to S100A4-staining groups of carcinoma cells, and antibodies to osteopontin significantly stained groups of carcinoma cells staining for ERalpha (P &amp;lt; 0.0001). There was a significant association of tumors staining for S100A4 with those with high vessel density (P = 0.021) and of tumors staining for osteopontin with those staining for ERalpha (P = 0.034). The association of staining for S100A4, osteopontin, or vessel density with patient death was significant (P &amp;lt; 0.0001, P = 0.005, and P = 0.014, respectively). The difference in cumulative proportion surviving between S100A4-positive patients with higher or lower vessel density increased up to about 12 years, but thereafter decreased to virtually zero after 18 years of follow-up. Patients with both S100A4-positive and osteopontin-positive primary tumors showed a statistically significant reduction in survival time over those with either one alone (P &amp;lt; 0.019), although in multivariate regression analysis, only staining for S100A4 was significant (P &amp;lt; 0.001). CONCLUSIONS: It is suggested that in human breast cancer, S100A4 exerts some of its effects through angiogenesis, and that osteopontin is dependent on ERalpha for its expression.