tbuckley/cabot-search huggingface dataset:
Burden of Illness in Cancer Survivors: Findings From a Population-Based National Sample
Authors: K. R. Yabroff, W. F. Lawrence, S. Clauser, W. W. Davis, M. L. Brown
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Population trends in aging and improved cancer survival are likely to result in increased cancer prevalence in the United States, but few estimates of the burden of illness among cancer survivors are currently available. The purpose of this study was to estimate the burden of illness in cancer survivors in a national, population-based sample. Methods: A total of 1823 cancer survivors and 5469 age-, sex-, and educational attainment–matched control subjects were identified from the 2000 National Health Interview Survey. Multiple measures of burden, including utility, a summary measure of health, and days lost from work, were compared using two-sided tests of statistical significance for the two groups overall and for subgroups stratified by tumor site and time since diagnosis. Results: Compared with matched control subjects, cancer survivors had poorer outcomes across all burden measures ( P <.01). Cancer survivors had lower utility values (0.74 versus 0.80; P <.001) and higher levels of lost productivity and were more likely to report their health as fair or poor (31.0% versus 17.9%; P <.001) than matched control subjects. Cancer survivors reported statistically significantly higher burden than did control subjects across tumor sites and across time since diagnosis (i.e., within the past year, 2–5 years, 6–10 years, and ≥11 years for the majority of measures. Conclusions: Cancer survivors have poorer health outcomes than do similar individuals without cancer across multiple burden measures. These decrements are consistent across tumor sites and are found in patients many years following reported diagnosis. Improved measurement of long-term burden of illness will be important for future prospective research.
Point Mutation in the Stalk of Angiotensin-Converting Enzyme Causes a Dramatic Increase in Serum Angiotensin-Converting Enzyme But No Cardiovascular Disease
Authors: Cornelis Kramers, Sergei M. Danilov, Jaap Deinum, Irina V. Balyasnikova, Nicole Scharenborg, Maaike Looman, Frans Boomsma, Marinus H. de Keijzer, Cornelia van Duijn, Sabrina Martin, Florent Soubrier, Gosse J. Adema
Journal: Circulation (2001)

Angiotensin-converting enzyme (ACE) metabolizes many small peptides and plays a key role in blood pressure regulation. Elevated serum ACE is claimed to be associated with an increased risk for cardiovascular disease. Previously, two families with dramatically increased serum ACE were described, but no systematic survey of affected individuals was performed, and the molecular background of this trait is unknown.Eight families were identified with autosomal dominant inheritance of a dramatic (5-fold) increase of serum ACE activity. Strikingly, no clinical abnormalities were apparent in the affected subjects. Isolated blood cells were used for genetic and biochemical analysis. The level of ACE expression on the blood leukocytes and dendritic cells and total cell-associated ACE of the affected individuals was similar to that in nonaffected relatives; however membrane-bound mutant ACE was much more efficiently clipped from the cell surface compared with its wild-type counterpart. A point mutation causing Pro1199Leu in the stalk region of the ACE molecule cosegregates with the increase in serum ACE (LOD score, 6.63).A point mutation in the stalk region of the ACE protein causes increased shedding, leading to increased serum ACE, whereas cell-bound ACE is unaltered, and affected individuals exhibit no clinical abnormalities. These findings qualify the importance of serum ACE and establish a new determinant of ACE solubilization.
The evolutionary analysis of the Tnt1 retrotransposon in Nicotiana species reveals the high variability of its regulatory sequences
Authors: S. Vernhettes, M. A. Grandbastien, J. M. Casacuberta
Journal: Molecular Biology and Evolution (1998)

We studied the evolution of the tobacco Tnt1 retrotransposon by analyzing Tnt1 partial sequences containing both coding domains and U3 regulatory sequences obtained from a number of Nicotiana species. We detected three different subfamilies of Tnt1 elements, Tnt1A, Tnt1B, and Tnt1C, that differ completely in their U3 regions but share conserved flanking coding and LTR regions. U3 divergence between the three subfamilies is found in the region that contains the regulatory sequences that control the expression of the well-characterized Tnt1-94 element. This suggests that expression of the three Tnt1 subfamilies might be differently regulated. The three Tnt1 subfamilies were present in the Nicotiana genome at the time of species divergence, but have evolved independently since then in the different genomes. Each Tnt1 subfamily seems to have conserved its ability to transpose in a limited and different number of Nicotiana species. Our results illustrate the high variability of Tnt1 regulatory sequences. We propose that this high sequence variability could allow these elements to evolve regulatory mechanisms in order to optimize their coexistence with their host genome.
Infant Respiratory Symptoms Associated with Indoor Heating Sources
Authors: Elizabeth W. Triche, Kathleen Belanger, William Beckett, Michael B. Bracken, Theodore R. Holford, Janneane Gent, Thomas Jankun, Jean-ellen McSharry, Brian P. Leaderer
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

This study examined the effects of indoor heating sources on infant respiratory symptoms during the heating season of the first year of life. Mothers delivering babies between 1993 and 1996 at 12 hospitals in Connecticut and Virginia were enrolled. Daily symptom and heating source use information about their infant was obtained every 2 weeks during the first year of life. Heating sources included fireplace, wood stove, kerosene heater, and gas space heater use. Four health outcomes were analyzed by reporting period: days of wheeze, episodes of wheeze, days of cough, and episodes of cough. A large percentage of infants had at least one episode of cough (88%) and wheeze (33%) during the heating season of the first year of life. Wood stove, fireplace, kerosene heater, and gas space heater use was intermittent across the study period. In adjusted Poisson regression models controlling for important confounders, gas space heater use was associated with episodes and days of wheeze. Wood stove use was associated with total days of cough, and kerosene heater use was associated with episodes of cough. Fireplace use was not associated with any of the respiratory symptoms. Use of some heating sources appears related to respiratory symptoms in infants.
Rural Health Care Access and Policy in Developing Countries
Authors: Roger Strasser, Sophia M. Kam, Sophie M. Regalado
Journal: Annual Review of Public Health (2015)

Compared to their urban counterparts, rural and remote inhabitants experience lower life expectancy and poorer health status. Nowhere is the worldwide shortage of health professionals more pronounced than in rural areas of developing countries. Sub-Saharan Africa (SSA) includes a disproportionately large number of developing countries; therefore, this article explores SSA in depth as an example. Using the conceptual framework of access to primary health care, sustainable rural health service models, rural health workforce supply, and policy implications, this article presents a review of the academic and gray literature as the basis for recommendations designed to achieve greater health equity. An alternative international standard for health professional education is recommended. Decision makers should draw upon the expertise of communities to identify community-specific health priorities and should build capacity to enable the recruitment and training of local students from underserviced areas to deliver quality health care in rural community settings.
Mutations in the interferon-sensitivity determining region of hepatitis C virus and transcriptional activity of the nonstructural region 5A protein
Authors: Toshiko Fukuma, Nobuyuki Enomoto, Fumiaki Marumo, Chifumi Sato
Journal: Hepatology (1998)

Amino acid (aa) mutations in the interferon-sensitivity determining region (ISDR) (aa position 237-276 of the nonstructural region 5A [NS5A] protein consisting of 447 amino acids) of hepatitis C virus (HCV) are related to increased interferon sensitivity and low viral load, but its mechanism has not been clarified. Recently, the NS5A protein has been reported to have a transcriptional activation function, like other viral transactivator proteins known to repress interferon-induced gene expression, and the ISDR overlaps one of the acidic amino acid regions, putative domains conferring this activity. In the present study, we investigated the transcriptional activation function of the ISDR itself and the effect of amino acid mutations in the ISDR on this activity. The full-length or truncated NS5A cDNA with different ISDR sequences was cloned into a yeast or mammalian expression vector to form a fusion protein consisting of the GAL4 DNA-binding domain (GAL4-DBD) and NS5A protein. Following transfection, the transcriptional activities of these constructs were determined using β-galactosidase (yeast) or chloramphenicol acetyltransferase (CAT) (mammalian cell) reporter gene expression under the control of GAL4 binding sites. In yeast, both the full-length sequence of NS5A-R (a clone with one aa mutation in the ISDR) and NS5A-S (a derivative of NS5A-R with six aa mutations in the ISDR) had no distinguishable transcriptional activity, whereas an amino-terminal deletion construct of NS5A-R (aa position 228-447) lacking 227 aa, showed remarkable activity with the relative value of 117.0 over that of the backbone vector. The same deletion mutant of NS5A-S produced five times higher activity with the relative value of 575.0, indicating that aa mutations in the ISDR profoundly affect this transcriptional activity. In a hepatoma cell line, HuH-7, the transcriptional activity was more prominent with a construct consisting of only the ISDR and short flanking sequences (aa 228-284) than larger deletion constructs of NS5A-R. Analysis using six different ISDR clones revealed that different mutations enhanced this activity to various extent compared with the wild-type ISDR. In particular, site-directed mutagenesis targeted to the aa position 252 showed that this aa residue had profound influence on the activity. These results suggest that the ISDR has a transcriptional activity, and it is enhanced by aa mutations that are also related to decreased viral load and increased interferon sensitivity. The possible association between transcriptional activation and interferon sensitivity or viral replication should be studied further.
Nationwide Study on Trends in Hospital Admissions for Major Cardiovascular Events and Procedures Among People With and Without Diabetes in England, 2004–2009
Authors: Eszter P. Vamos, Christopher Millett, Camille Parsons, Paul Aylin, Azeem Majeed, Alex Bottle
Journal: Diabetes Care (2011)

OBJECTIVE It is unclear whether people with and without diabetes equally benefitted from reductions in cardiovascular disease (CVD). We aimed to compare recent trends in hospital admission rates for angina, acute myocardial infarction (AMI), stroke, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) among people with and without diabetes in England. RESEARCH DESIGN AND METHODS We identified all patients aged &amp;gt;16 years with cardiovascular events in England between 2004–2005 and 2009–2010 using national hospital activity data. Diabetes- and nondiabetes-specific rates were calculated for each year. To test for time trend, we fitted Poisson regression models. RESULTS In people with diabetes, admission rates for angina, AMI, and CABG decreased significantly by 5% (rate ratio 0.95 [95% CI 0.94–0.96]), 5% (0.95 [0.93–0.97]), and 3% (0.97 [0.95–0.98]) per year, respectively. Admission rates for stroke did not significantly change (0.99 [0.98–1.004]) but increased for PCI (1.01 [1.005–1.03]) in people with diabetes. People with and without diabetes experienced similar proportional changes for all outcomes, with no significant differences in trends between these groups. However, diabetes was associated with an ~3.5- to 5-fold risk of CVD events. In-hospital mortality rates declined for AMI and stroke, remained unchanged for CABG, and increased for PCI admissions in both groups. CONCLUSIONS This national study suggests similar changes in admissions for CVD in people with and without diabetes. Aggressive risk reduction is needed to further reduce the high absolute and relative risk of CVD still present in people with diabetes.
CYP2D6 Metabolism and Patient Outcome in the Austrian Breast and Colorectal Cancer Study Group Trial (ABCSG) 8
Authors: Matthew P. Goetz, Vera J. Suman, Tanya L. Hoskin, Michael Gnant, Martin Filipits, Stephanie L. Safgren, Mary Kuffel, Raimund Jakesz, Margaretha Rudas, Richard Greil, Otto Dietze, Alois Lang, Felix Offner, Carol A. Reynolds, Richard M. Weinshilboum, Matthew M. Ames, James N. Ingle
Journal: Clinical Cancer Research (2012)

Controversy exists about CYP2D6 genotype and tamoxifen efficacy.A matched case-control study was conducted using the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG8) that randomized postmenopausal women with estrogen receptor (ER)-positive breast cancer to tamoxifen for 5 years (arm A) or tamoxifen for 2 years followed by anastrozole for 3 years (arm B). Cases had disease recurrence, contralateral breast cancer, second non-breast cancer, or died. For each case, controls were identified from the same treatment arm of similar age, surgery/radiation, and tumor-node-metastasis (TNM) stage. Genotyping was conducted for alleles associated with no (PM; *3, *4, *6), reduced (IM; *10, and *41), and extensive (EM: absence of these alleles) CYP2D6 metabolism.The common CYP2D6*4 allele was in Hardy-Weinberg equilibrium. In arm A during the first 5 years of therapy, women with two poor alleles [PM/PM: OR, 2.45; 95% confidence interval (CI), 1.05-5.73, P = 0.04] and women with one poor allele (PM/IM or PM/EM: OR, 1.67; 95% CI, 0.95-2.93; P = 0.07) had a higher likelihood of an event than women with two extensive alleles (EM/EM). In years 3 to 5 when patients remained on tamoxifen (arm A) or switched to anastrozole (arm B), PM/PM tended toward a higher likelihood of a disease event relative to EM/EM (OR, 2.40; 95% CI, 0.86-6.66; P = 0.09) among women on arm A but not among women on arm B (OR, 0.28; 95% CI, 0.03-2.30).In ABCSG8, the negative effects of reduced CYP2D6 metabolism were observed only during the period of tamoxifen administration and not after switching to anastrozole.
Surgery for mental illness has been proved effective
Authors: R P Snaith
Journal: BMJ (1997)

Editor–Sandra Goldbeck-Wood reports that Norway has offered compensation to all patients who have had a lobotomy in Norway in the past.1 Her article seems to leave the opponents of psychosurgery on a high moral ground. What the Norwegian fiscal administration chooses to do with presumably surplus money is its own decision, but Goldbeck-Wood's use of the word “victims” implies that patients who had a leucotomy in the past were the subjects of …
Predictive factors of early postoperative graft function in human liver transplantation
Authors: Xavier F. González, Antoni Rimola, Luis Grande, Maria Antolin, Juan C. Garcia-Valdecasas, Jose Fuster, Antonio M. Lacy, Esteban Cugat, Jose Visa, Joan Rodés
Journal: Hepatology (1994)

To identify factors predictive of early postoperative graft function, we analyzed 54 variables—including easily available clinical and laboratory data prospectively obtained from organ donors, transplant recipients and surgical procedures in 168 consecutive liver transplantations. Early postoperative graft function was classified into three groups according to a scoring system ranging from 3 to 9 based on peak serum ALT values, mean bile output and lowest prothrombin activity measured during the 72 hr after transplant: group 1 (score 3 to 4, good graft function; n = 73), group 2 (score 5 to 6, moderate dysfunction; n = 50) and group 3 (score, 7 to 9, severe dysfunction; n = 45). In univariate analyses, 8 of the 54 variables analyzed were statistically significant (p &lt; 0.05) predictors of severe graft dysfunction: high serum sodium concentration and brain death caused by cranial trauma in organ donors, advanced age and low prothrombin activity in transplant recipients, prolonged total ischemia time and large transfusions of red blood cells, fresh frozen plasma and platelets during surgery. After introduction of these eight variables in a multivariate analysis, only four were found to independently predict early postoperative graft function: donor serum sodium concentration, total ischemia time, platelet transfusion during surgery and recipient prothrombin activity. In 52 liver transplantations, in which the predictive value of liver tissue adenine nucleotide concentration and several biochemical sensitive markers of donor nutritional status was also analyzed, only the ATP level in liver tissue obtained at the time of organ reperfusion was identified as an independent predictor of initial graft function. We conclude that the degree of early postoperative graft dysfunction in liver transplantation can be predicted on the basis of data from organ donors, transplant recipients and surgical events. (Hepatology 1994;20:565-573).
Cytoprotective role of heme oxygenase (HO)-1 in human kidney with various renal diseases
Authors: Kayoko Morimoto, Kazuhide Ohta, Akihiro Yachie, Yonghong Yang, Masaki Shimizu, Chinami Goto, Tomoko Toma, Yoshihito Kasahara, Hitoshi Yokoyama, Toshio Miyata, Hidetoshi Seki, Shoichi Koizumi
Journal: Kidney International (2001)
Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma
Authors: Sonja Hahtola, Soile Tuomela, Laura Elo, Tiina Häkkinen, Leena Karenko, Boguslaw Nedoszytko, Hannele Heikkilä, Ulpu Saarialho-Kere, Jadwiga Roszkiewicz, Tero Aittokallio, Riitta Lahesmaa, Annamari Ranki
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes. Experimental Design: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4+ cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression. Results: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations. Conclusions: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.
Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry
Authors: Sangmee Bae, Rajeev Saggar, Marcy B Bolster, Lorinda Chung, Mary Ellen Csuka, Chris Derk, Robyn Domsic, Aryeh Fischer, Tracy Frech, Avram Goldberg, Monique Hinchcliff, Vivien Hsu, Laura Hummers, Elena Schiopu, Maureen D Mayes, Vallerie McLaughlin, Jerry Molitor, Nausheen Naz, Daniel E Furst, Paul Maranian, Virginia Steen, Dinesh Khanna
Journal: Annals of the Rheumatic Diseases (2012)

Patients with normal (mean pulmonary arterial pressure (mPAP) ≤20 mm Hg) and borderline mean pulmonary pressures (21-24 mm Hg) are "at risk" of developing pulmonary hypertension (PH). The objectives of this analysis were to examine the baseline characteristics in systemic sclerosis (SSc) with normal and borderline mPAP and to explore long-term outcomes in SSc patients with borderline mPAP versus normal haemodynamics.PHAROS is a multicentre prospective longitudinal cohort of patients with SSc "at risk" or recently diagnosed with resting PH on right heart catheterisation (RHC). Baseline clinical characteristics, pulmonary function tests, high-resolution CT, 2-dimensional echocardiogram and RHC results were analysed in normal and borderline mPAP groups.206 patients underwent RHC (results showed 35 normal, 28 borderline mPAP, 143 resting PH). There were no differences in the baseline demographics. Patients in the borderline mPAP group were more likely to have restrictive lung disease (67% vs 30%), fibrosis on high-resolution CT and a higher estimated right ventricular systolic pressure on echocardiogram (46.3 vs 36.2 mm Hg; p<0.05) than patients with normal haemodynamics. RHC revealed higher pulmonary vascular resistance and more elevated mPAP on exercise (≥30; 88% vs 56%) in the borderline mPAP group (p<0.05 for both). Patients were followed for a mean of 25.7 months and 24 patients had a repeat RHC during this period. During follow-up, 55% of the borderline mPAP group and 32% of the normal group developed resting PH (p=NS).Patients with borderline mPAP have a greater prevalence of abnormal lung physiology, pulmonary fibrosis and the presence of exercise mPAP ≥30 mm Hg.
Representation and knowledge are not the same thing
Authors: Leslie Smith
Journal: Behavioral and Brain Sciences (1999)

Two standard epistemological accounts are conflated in Dienes &amp; Perner's account of knowledge, and this conflation requires the rejection of their four conditions of knowledge. Because their four metarepresentations applied to the explicit-implicit distinction are paired with these conditions, it follows by modus tollens that if the latter are inadequate, then so are the former. Quite simply, their account misses the link between true reasoning and knowledge.
Differences in Skin Prick Test Reactivity Between Body and Faecal Extracts of Dermatophagoides pteronyssinus in Two Spanish Cities
Authors: V IRAOLA, M BOQUETE, A FERRER, C CARBALLAS, C ALMUINA, F CARBALLADA, C ANDREU, J CARNES, M GALLEGO, M CASANOVAS
Journal: Journal of Allergy and Clinical Immunology (2008)