tbuckley/cabot-search huggingface dataset:
Practice based education to improve delivery systems for prevention in primary care: randomised trial
Authors: Peter A Margolis, Carole M Lannon, Jayne M Stuart, Bruce J Fried, Lynette Keyes-Elstein, Donald E Moore
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To examine the effectiveness of an intervention that combined continuing medical education with process improvement methods to implement "office systems" to improve the delivery of preventive care to children. <b>Design</b> Randomised trial in primary care practices. <b>Setting</b> Private paediatric and family practices in two areas of North Carolina. <b>Participants</b> Random sample of 44 practices allocated to intervention and control groups. <b>Intervention</b> Practice based continuing medical education in which project staff coached practice staff in reviewing performance and identifying, testing, and implementing new care processes (such as chart screening) to improve delivery of preventive care. <b>Main outcome measure</b> Change over time in the proportion of children aged 24-30 months who received age appropriate care for four preventive services (immunisations, and screening for tuberculosis, anaemia, and lead). <b>Results</b> The proportion of children per practice with age appropriate delivery of all four preventive services changed, after a one year period of implementation, from 7% to 34% in intervention practices and from 9% to 10% in control practices. After adjustment for baseline differences in the groups, the change in the prevalence of all four services between the beginning and the end of the study was 4.6-fold greater (95% confidence interval 1.6 to 13.2) in intervention practices. Thirty months after baseline, the proportion of children who were up to date with preventive services was higher in intervention than in control practices; results for screening for tuberculosis (54% <i>v</i> 32%), lead (68% <i>v</i> 30%), and anaemia (79% <i>v</i> 71%) were statistically significant (P &lt; 0.05). <b>Conclusion</b> Continuing education combined with process improvement methods is effective in increasing rates of delivery of preventive care to children.
Clinical Studies of 6-Azauracil
Authors: Bruce I. Shnider, Emil Frei, John H. Tuohy, John Gorman, Emil J. Freireich, Clyde O. Brindley, John Clements
Journal: Cancer Research (1960)

Summary  Toxicity studies with the pyrimidine analog, 6-azauracil, have revealed that the major and perhaps the only adverse effects relate to the central nervous system. These effects usually manifest themselves initially as lethargy, but may go on to a wide spectrum of sensory and motor abnormalities. Electroencephalographic changes regularly occur, and these often precede the clinical effects. The effects of dose schedule and duration of 6-azauracil administration are reported. Children are more susceptible to the effects of 6-azauracil than are adults. A closely related compound, 6-azathymine, produces similar electroencephalographic changes. Attempts to reverse the toxic effects of 6-azauracil with various metabolites were unsuccessful. The above findings, along with several ancillary observations, are presented and discussed.
Adaptation and Constraint at Toll-Like Receptors in Primates
Authors: G. Wlasiuk, M. W. Nachman
Journal: Molecular Biology and Evolution (2010)

Frequent positive selection is a hallmark of genes involved in the adaptive immune system of vertebrates, but the incidence of positive selection for genes underlying innate immunity in vertebrates has not been well studied. The toll-like receptors (TLRs) of the innate immune system represent the first line of defense against pathogens. TLRs lie directly at the host-environment interface, and they target microbial molecules. Because of this, they might be subject to frequent positive selection due to coevolutionary dynamics with their microbial counterparts. However, they also recognize conserved molecular motifs, and this might constrain their evolution. Here, we investigate the evolution of the ten human TLRs in the framework of these competing ideas. We studied rates of protein evolution among primate species and we analyzed patterns of polymorphism in humans and chimpanzees. This provides a window into TLR evolution at both long and short timescales. We found a clear signature of positive selection in the rates of substitution across primates in most TLRs. Some of the implicated sites fall in structurally important protein domains, involve radical amino acid changes, or overlap with polymorphisms with known clinical associations in humans. However, within species, patterns of nucleotide variation were generally compatible with purifying selection, and these patterns differed between humans and chimpanzees and between viral and nonviral TLRs. Thus, adaptive evolution at TLRs does not appear to reflect a constant turnover of alleles and instead might be more episodic in nature. This pattern is consistent with more ephemeral pathogen-host associations rather than with long-term coevolution.
Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
Authors: Yung-Jue Bang, Eric Van Cutsem, Andrea Feyereislova, Hyun C Chung, Lin Shen, Akira Sawaki, Florian Lordick, Atsushi Ohtsu, Yasushi Omuro, Taroh Satoh, Giuseppe Aprile, Evgeny Kulikov, Julie Hill, Michaela Lehle, Josef Rüschoff, Yoon-Koo Kang
Journal: The Lancet (2010)
Klebsiella 'modifying factor': binding studies with HLA-B27+ and B27- lymphocytes.
Authors: J A Trapani, I F McKenzie
Journal: Annals of the Rheumatic Diseases (1985)

On the basis that extracts of some klebsiella organisms bind selectively to the lymphocytes of HLA-B27+ individuals and induce the appearance of new antigens, attempts were made to detect the binding of klebsiella products to HLA-B27+ and B27- lymphocytes by a number of different techniques. Firstly, blocking of the binding of two different HLA-B27 specific monoclonal antibodies to HLA-B27+ lymphocytes has been examined following exposure of the lymphocytes to a cell-free culture filtrate from K. pneumoniae K21 and K43. There was no reduction in the cytotoxicity of either antibody, suggesting that neither of the epitopes detected by the anti-HLA-B27 monoclonal antibodies is a binding site for klebsiella products. Secondly, we have studied the binding of partially purified, radiolabelled klebsiella products to healthy HLA-B27+ and B27- lymphocytes. There was no significant difference either in terms of numerical counts bound or by comparing, by SDS-PAGE analysis, the molecules bound to each cell type. At the level of sensitivities of these techniques we can detect no difference in binding of klebsiella products to the lymphocytes of healthy HLA-B27+ and B27- individuals.
Striatal Functional Alteration During Incentive Anticipation in Pediatric Anxiety Disorders
Authors: Amanda E. Guyer, Victoria R. Choate, Allison Detloff, Brenda Benson, Eric E. Nelson, Koraly Perez-Edgar, Nathan A. Fox, Daniel S. Pine, Monique Ernst
Journal: American Journal of Psychiatry (2011)

Objective: Behavioral inhibition is an early childhood temperament recently associated with altered striatal response in adolescence to incentives of increasing magnitudes. Since early childhood behavioral inhibition is also associated with risk for adolescent social phobia, a similar pattern of striatal activation may manifest in social phobia. The present study compares striatal function in healthy adolescents, adolescents with social phobia, and adolescents with generalized anxiety disorder. Method: Blood-oxygen-level-dependent signal in striatal regions was examined in 58 medication-free adolescents—14 with social phobia, 18 with generalized anxiety disorder but not social phobia, and 26 with no psychiatric disorder—matched on sex, age, puberty, IQ, and socioeconomic status. During functional magnetic resonance imaging, participants responded to incentive cues depicting potential monetary gains or losses of varying magnitudes. Results: While anticipating incentives of increasing magnitude, adolescents with social phobia showed increasingly heightened caudate and putamen activation at a level greater than that seen in the healthy comparison and generalized anxiety disorder groups. The generalized anxiety disorder group showed a unique valence-specific putamen response relative to the healthy comparison or social phobia group. Both patient groups displayed more complex patterns in the nucleus accumbens than in the caudate or putamen. Conclusions: Caudate and putamen hypersensitivity to incentives of increasing magnitudes characterizes adolescent social phobia, relative to activation in this region in adolescents with generalized anxiety disorder as well as healthy adolescents. Thus, these findings resemble the pattern previously found in adolescents with early childhood behavioral inhibition, thereby implicating similar neural responses to anticipation of incentives in both early childhood behavioral inhibition and adolescent social phobia.
Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer
Authors: Nicole M White, Christopher R Cabanski, Jessica M Silva-Fisher, Ha X Dang, Ramaswamy Govindan, Christopher A Maher
Journal: Genome biology (2014)

Long intergenic non-coding RNAs (lncRNAs) represent an emerging and under-studied class of transcripts that play a significant role in human cancers. Due to the tissue- and cancer-specific expression patterns observed for many lncRNAs it is believed that they could serve as ideal diagnostic biomarkers. However, until each tumor type is examined more closely, many of these lncRNAs will remain elusive.Here we characterize the lncRNA landscape in lung cancer using publicly available transcriptome sequencing data from a cohort of 567 adenocarcinoma and squamous cell carcinoma tumors. Through this compendium we identify over 3,000 unannotated intergenic transcripts representing novel lncRNAs. Through comparison of both adenocarcinoma and squamous cell carcinomas with matched controls we discover 111 differentially expressed lncRNAs, which we term lung cancer-associated lncRNAs (LCALs). A pan-cancer analysis of 324 additional tumor and adjacent normal pairs enable us to identify a subset of lncRNAs that display enriched expression specific to lung cancer as well as a subset that appear to be broadly deregulated across human cancers. Integration of exome sequencing data reveals that expression levels of many LCALs have significant associations with the mutational status of key oncogenes in lung cancer. Functional validation, using both knockdown and overexpression, shows that the most differentially expressed lncRNA, LCAL1, plays a role in cellular proliferation.Our systematic characterization of publicly available transcriptome data provides the foundation for future efforts to understand the role of LCALs, develop novel biomarkers, and improve knowledge of lung tumor biology.
Effect of 9p21.3 Coronary Artery Disease Locus Neighboring Genes on Atherosclerosis in Mice
Authors: Juyong Brian Kim, Andres Deluna, Imran N. Mungrue, Christine Vu, Delila Pouldar, Mete Civelek, Luz Orozco, Judy Wu, Xuping Wang, Sarada Charugundla, Lawrence W. Castellani, Marta Rusek, Hieronim Jakubowski, Aldons J. Lusis
Journal: Circulation (2012)

Background— The human 9p21.3 chromosome locus has been shown to be an independent risk factor for atherosclerosis in multiple large-scale genome-wide association studies, but the underlying mechanism remains unknown. We set out to investigate the potential role of the 9p21.3 locus neighboring genes, including Mtap , the 2 isoforms of Cdkn2a, p16Ink4a and p19Arf, and Cdkn2b , in atherosclerosis using knockout mice models. Methods and Results— Gene-targeted mice for neighboring genes, including Mtap , Cdkn2a , p19Arf , and Cdkn2b , were each bred to mice carrying the human APO*E3 Leiden transgene that sensitizes the mice for atherosclerotic lesions through elevated plasma cholesterol. We found that the mice heterozygous for Mtap developed larger lesions compared with wild-type mice (49623±21650 versus 18899±9604 μm 2 per section [mean±SD]; P =0.01), with morphology similar to that of wild-type mice. The Mtap heterozygous mice demonstrated changes in metabolic and methylation profiles and CD4 + cell counts. The Cdkn2a knockout mice had smaller lesions compared with wild-type and heterozygous mice, and there were no significant differences in lesion size in p19Arf and Cdkn2b mutants compared with wild type. We observed extensive, tissue-specific compensatory regulation of the Cdkn2a and Cdkn2b genes among the various knockout mice, making the effects on atherosclerosis difficult to interpret. Conclusions— Mtap plays a protective role against atherosclerosis, whereas Cdkn2a appears to be modestly proatherogenic. However, no relation was found between the 9p21 genotype and the transcription of 9p21 neighboring genes in primary human aortic vascular cells in vitro. There is extensive compensatory regulation in the highly conserved 9p21 orthologous region in mice.
Mammographic Density, Response to Hormones, and Breast Cancer Risk
Authors: Norman F. Boyd, Olga Melnichouk, Lisa J. Martin, Greg Hislop, Anna M. Chiarelli, Martin J. Yaffe, Salomon Minkin
Journal: Journal of Clinical Oncology (2011)

Percent mammographic density (PMD) is a strong risk factor for breast cancer that changes in response to changes in hormone exposure. We have examined the magnitude of the association of hormone exposure with PMD according to subsequent breast cancer risk.In three case-control studies, with 1,164 patient cases and 1,155 controls nested in cohorts of women screened with mammography, we examined the association of PMD measured in the baseline mammogram with risk of breast cancer in the following 1 to 8 years (mean, 3 years), according to use of oral contraceptives (OCs) in premenopausal women, menopause, and hormone therapy (HT) in postmenopausal women. All statistical comparisons are adjusted for age and other risk factors.In premenopausal women who later developed breast cancer (patient cases), PMD was 5.3% greater in past users of OCs than in nonusers (P = .06). In controls, OC users had 2% less density than nonusers (P = .44; test for interaction P = .06). The difference in PMD between premenopausal and postmenopausal women for patient cases was 8.5% (P < .001) and for controls, 3.9% (P = .01; test for interaction P = .03). In postmenopausal women, PMD was 6% greater in patients who used HT than in never users (P < .001). Controls who used HT had 1.6% greater PMD (P = .26) than never users (test for interaction P = .001). Differences in PMD resulted mainly from differences in the dense area of the mammogram.Differences in PMD associated with differences in hormone exposure were greater in women who later developed breast cancer than in controls in each of the hormone exposures examined.
THE CLIMATE OF COLORADO FOR RESPIRATORY DISEASES.
Authors: CHARLES DENISON
Journal: JAMA (1898)

<h3>PART II:—SENSIBLE TEMPERATURE AND THE EXPERIENCE OF INVALIDS, WITH CONTRAINDICATIONS FOR THE HIGH ALTITUDE CLIMATE.</h3><h3>Variability versus equability.</h3> —The study of temperature ranges assumes importance from the undue weight given by the medical profession and the laity to supposed injurious effects of thermal changes. Let us investigate and see if it is the dampness and not the thermal oscillation which is responsible for the injury. How uniformly variability goes with dryness and equability with moisture may be illustrated by the daily and monthly ranges of temperature at places which represent dry and moist climates. Chosen without reference to this particular evidence, twenty-five<i>dry</i>and twenty-five<i>moist</i>prominent signal stations and health resorts in the United States give the following remarkable average excesses of mean daily temperature ranges. The excess of the dryest one-fourth over the moistest one-fourth of them is 22.9 degrees, and the same average excess for the monthly
Monocyte Telomere Shortening and Oxidative DNA Damage in Type 2 Diabetes
Authors: Mike J. Sampson, Mark S. Winterbone, Jackie C. Hughes, Nicoletta Dozio, David A. Hughes
Journal: Diabetes Care (2006)

OBJECTIVE—Telomeres are DNA sequences necessary for DNA replication, which shorten at cell division at a rate related to levels of oxidative stress. Once shortened to a critical length, cells are triggered into replicative senescence. Type 2 diabetes is associated with oxidative DNA damage, and we hypothesized that telomere shortening would characterize type 2 diabetes. RESEARCH DESIGN AND METHODS—We studied 21 male type 2 diabetic subjects (mean age 61.2 years, mean HbA1c 7.9%) selected to limit confounding effects on telomere length and 29 matched control subjects. Telomere length was measured in peripheral venous monocyte and T-cells (naïve and memory) by fluorescent in situ hybridization and oxidative DNA damage by flow cytometry of oxidized DNA bases. Peripheral insulin resistance (homeostasis model assessment) and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS—Mean monocyte telomere length in the diabetic group was highly significantly lower than in control subjects (4.0 [1.1] vs. 5.5 [1.1]; P &amp;lt; 0.0001), without significant differences in lymphocyte telomere length. There was a trend toward increased oxidative DNA damage in all diabetes cell types examined and a significant inverse relationship between oxidative DNA damage and telomere length (r = −0.55; P = 0.018) in the diabetic group. Telomere length was unrelated to plasma CRP concentration or insulin resistance. CONCLUSIONS—Monocyte telomere shortening in type 2 diabetes could be due to increased oxidative DNA damage to monocyte precursors during cell division. This data suggests that monocytes adhering to vascular endothelium and entering the vessel wall in type 2 diabetes are from a population with shorter telomeres and at increased risk of replicative senescence within vascular plaque.
The dual nature of the language faculty
Authors: Harald Clahsen
Journal: Behavioral and Brain Sciences (1999)

The following discussion aims to illuminate further the way in which morphologically complex words are represented in the mental lexicon. It is argued that the dual-mechanism model can accommodate the linguistic and psycholinguistic evidence currently available, not only on German inflection (as pointed out in the target article) but also on other languages (as presented in several commentaries). Associative single-mechanism models of inflection, on the other hand, provide only partial accounts.
Mechanism of Increased Parathyroid Hormone mRNA in Experimental Uremia
Authors: CEVDET YALCINDAG, JUSTIN SILVER, TALLY NAVEH-MANY
Journal: Journal of the American Society of Nephrology (1999)

Patients with chronic renal failure develop secondary hyperparathyroidism with increased synthesis and secretion of parathyroid hormone (PTH) resulting in severe skeletal complications. In rats with secondary hyperparathyroidism due to 5/6 nephrectomy, there are increased PTH mRNA levels, and this mechanism was studied. Parathyroid glands were microdissected from control and 5/6 nephrectomy rats and analyzed for PTH mRNA and control genes, and the nuclei were used for nuclear run-on experiments. The cytosolic proteins of the parathyroids were used to study PTH mRNA protein binding by ultraviolet cross-linking and the degradation of the PTH transcript in vitro. Nuclear run-ons showed that the increase in PTH mRNA levels was posttranscriptional. Protein binding to the PTH mRNA 3'-UTR determines PTH mRNA stability and levels. Parathyroid proteins from uremic rats bound PTH mRNA similar to control rats by ultraviolet cross-linking. To determine the effect of uremia on PTH mRNA stability, an in vitro RNA degradation assay was performed with parathyroid proteins from uremic rats. When parathyroid proteins from control rats were incubated with PTH mRNA, there was transcript degradation already at 30 min, reaching 50% at 60 min and 90% at 180 min. With uremic parathyroid proteins, the PTH mRNA was not degraded at all at 120 min and was moderately decreased at 180 min. This decrease in degradation by uremic parathyroid proteins suggests a decrease in parathyroid cytosolic endonuclease activity in uremia resulting in a more stable PTH transcript. The increased PTH mRNA levels would translate into increased PTH synthesis and serum PTH levels, which would lead to metabolic bone disease in many patients with chronic renal failure.
Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.
Authors: G M Strauss, D J Kwiatkowski, D H Harpole, T J Lynch, A T Skarin, D J Sugarbaker
Journal: Journal of Clinical Oncology (1995)

Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively.Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed.Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome.At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies.
DISEASES OF THE RESPIRATORY SYSTEM CIRCULATION THROUGH THE LUNG AND DIFFUSION OF GASES
Authors: Joseph L. Lilienthal, Richard L. Riley
Journal: Annual Review of Medicine (1954)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility
Authors: Miles Parkes, Jeffrey C Barrett, Natalie J Prescott, Mark Tremelling, Carl A Anderson, Sheila A Fisher, Roland G Roberts, Elaine R Nimmo, Fraser R Cummings, Dianne Soars, Hazel Drummond, Charlie W Lees, Saud A Khawaja, Richard Bagnall, Denis A Burke, Catherine E Todhunter, Tariq Ahmad, Clive M Onnie, Wendy McArdle, David Strachan, Graeme Bethel, Claire Bryan, Cathryn M Lewis, Panos Deloukas, Alastair Forbes, Jeremy Sanderson, Derek P Jewell, Jack Satsangi, John C Mansfield, Lon Cardon, Christopher G Mathew
Journal: Nature Genetics (2007)