tbuckley/cabot-search huggingface dataset:
Abstract P125: The Association Between Chronic Obstructive Pulmonary Disease and Cognitive Status in an Elderly Sample Using the Third National Health and Nutrition Examination Survey
Authors: Ayesha Sherzai, Joshua Z Willey, Sonia Vega, Dean Sherzai
Journal: Circulation (2015)

Introduction: Dementia and cognitive impairment is a major public health issue and is likely related to complex interaction between genetics and modifiable risk factors. Chronic Obstructive Pulmonary Disease (COPD) has been associated with dementia, but its relationship with specific cognitive deficits has not been previously explored. Methods: Data was analyzed from the Third National Health and Nutrition Examination Survey (NHANES III). Cases of COPD were defined by a ratio of forced expiratory volume to forced vital capacity of &lt; 0.7. The three cognitive tests included 1) three word immediate verbal memory test (9 points), 2) delayed verbal memory test (9 points), and 3) serial subtractions test (5 trials), as a surrogate of executive function. The odds of having poor cognitive status was assessed using logistic regression models between COPD and each of the three cognitive tests. Models were furthers adjusted for demographic variables, including age, sex, height, body mass index education, race, poverty income ratio, and medical coverage, smoking, and medical comorbidities. Results: We identified individuals 60-89 years of age (weighted N= 17,181,182) with a diagnosis of COPD (mean age 71.5 ± 0.19 years, 50.1% women, 85.9% non-Hispanic whites). In the unadjusted model, there was a strong association between COPD and poor scores for immediate memory recall (&lt;5 out of 9 points; OR 2.18, 95% CI 1.81-2.62), delayed memory recall (&lt;4 out of 9 points; OR 2.25, 95% CI 1.85-2.70) and serial subtraction (&lt; 5 trials correct; OR 1.44, 95% CI 1.10-1.90). After adjusting for socio-demographic and vascular variables, these relationships remained robust for the immediate and delayed recall tests. In contrast, the association with serial subtraction test was rendered insignificant after adjusting for socio-demographic factors (OR 1.05, 95% CI 0.69-1.60). Upon further adjusting for vascular risk factors such as stroke, coronary heart disease, hypertension, diabetes and congestive heart failure, the odds for poor serial subtraction test increased and became significant (OR 2.74, 95% CI 1.17-6.40, p trend &lt; 0.001). Discussion: In this nationally representative database, COPD is significantly associated with impaired immediate and delayed memory, but not with executive function. These results shed light on differential susceptibility of the brain in COPD and its relationship with vascular risk factors.
People die everywhere, so care should be optimised in all settings and all along the way
Authors: Scott A Murray, Sébastien Moine
Journal: BMJ (2015)

Impaired α7 nicotinic receptor (nAChR) function and GABAergic transmission in the hippocampus and elevated brain levels of kynurenic acid (KYNA), an astrocyte-derived metabolite of the kynurenine pathway, are key features of schizhophrenia. KYNA acts as a non-competitive antagonist with respect to agonists at both α7 nAChRs and NMDA receptors. Here, we tested the hypothesis that in hippocampal slices tonically active α7 nAChRs control GABAergic transmission to CA1 pyramidal neurons and are sensitive to inhibition by rising levels of KYNA. The α7 nAChR-selective antagonistα -bungarotoxin (α BGT, 100 nM) and methyllycaconitine (MLA, 10 nM), an antagonist at α7 and other nAChRs, reduced by 51.3 ± 1.3% and 65.2 ± 1.5%, respectively, the frequency of GABAergic PSCs recorded from CA1 pyramidal neurons. MLA had no effect on miniature GABAergic PSCs. Thus, GABAergic synaptic activity in CA1 pyramidal neurons is maintained, in part, by tonically active α7 nAChRs located on the somatodendritic and/or preterminal region of axons of interneurons that synapse onto the neurons under study. L-kynurenine (20 or 200 μM) or KYNA (20-200 μM) suppressed concentration dependently the frequency of GABAergic PSCs; the inhibitory effect of 20 μM L-kynurenine had an onset time of about 35 min and could not be detected in the presence of 100 nM α-BGT. These results suggest that KYNA levels generated from 20 μM kynurenine inhibit tonically active α7 nAChR-dependent GABAergic transmission to the pyramidal neurons. Disruption of nAChR-dependent GABAergic transmission by mildly elevated levels of KYNA can be an important determinant of the cognitive deficits presented by patients with schizophrenia.
Genetic variation in human RHS7 of the TH2 locus control region influences DNA methylation and is associated with IgE
Authors: Maximilian Schieck, Vishwas Sharma, Sven Michel, Antoaneta A. Toncheva, Daniel P. Potaczek, Luise Worth, Jon Genuneit, Anja Kretschmer, Martin Depner, Jean-Charles Dalphin, Josef Riedler, Remo Frei, Juha Pekkanen, Jörg Tost, Michael Kabesch
Journal: European Respiratory Journal (2014)

Background: Previously, polymorphisms in the TH2 cytokine locus on chromosome 5q31 showed associations with asthma and IgE (Li X. et al. J Allergy Clin Immunol 2010; 125(2):328-335e11). While the locus contains interleukins (IL) 4, 5 and 13 essential for TH2 differentiation the strongest association signal mapped to the RAD50 gene. In mice, Rad50 harbors an epigenetic locus control region defined by four Rad50 DNase I hypersensitive sites (RHS4-7) of which RHS7 undergoes the strongest regulatory changes during TH2 differentiation (Lee G.R. et al. Nat Immunol 2005; 6(1):42-48). We investigated if the human homolog of RHS7 influences TH2 locus gene expression or DNA methylation and if associations with asthma or IgE exist.

Methods: Human RHS7 was fine mapped for polymorphisms based on 1000 Genomes data. Allele-specific changes in transcription factor binding were analyzed with electrophoretic mobility shift assays. Effects on mRNA expression ( RAD50 , IL4 , IL13 ) were measured in whole blood (n=100 adults). Differences in DNA methylation were studied in cord blood (n=73) and at age 4.5 years (n=61) in the PASTURE cohort. Genetic association with childhood asthma or total serum IgE was tested in the MAGICS/ISAAC II population (n=1,145).

Results: Fine mapping identified the polymorphism rs2240032 to be located in RHS7. Allele-specific transcription factor binding was observed in EMSA. Furthermore, significant polymorphism effects were present on methylation in the IL13 promoter region (cord blood: p =0.003; age 4.5 years: p =0.032) and on IgE levels ( p =0.023).

Conclusion : Polymorphism rs2240032 in the TH2 cytokine locus influences 5q31 DNA methylation and total IgE levels.
Correlation of total sleep time (TST) by SenseWear Armband (SWA®) and nocturnal polysomnography (NPSG), in a population with and without OSA
Authors: A. O'Brien, A. McGowan, L. Stewart, K. Fennell, K. Bolger, J. Faul, L. Cormican
Journal: European Respiratory Journal (2012)

Portable devices that determine TST may act as an adjunct to level 3 diagnostic tests for OSA. The SWA is such and measures TST using a proprietary algorithm. Calculation of TST could improve the accuracy of a level 3 diagnostic device.  Aim: Correlation of TST by SWA and NPSG, in a population with and without sleep apnoea.  89 consecutive patients undergoing NPSG because of a suspicion of OSA wore an SWA on the same night. Patients were stratified by the presence and severity of OSA. Correlation coefficient for TST were determined between SWA and NPSG for all subjects and in the OSA subgroups.  The prevalence of a normal PSG, mild moderate and severe OSA was 22 (24.7%), 31 (34.8%), 12 (13.4%) and 24 (26.9%) of 89 subjects. and the respective correlation coefficients were r=0.68, 0.74, 0.85 and 0.25. Clinically important differences are presented with Bland Altman plots (Fig. 1 & 2).  Correlation of TST between the two methods was weakest in those with severe OSA. The determination of TST by SWA in a population with severe OSA is likely to be unreliable. NPSG remains the gold standard for determination of TST.
Philadelphia chromosome and terminal transferase-positive acute leukemia: similarity of terminal phase of chronic myelogenous leukemia and de novo acute presentation.
Authors: K Jain, Z Arlin, R Mertelsmann, T Gee, S Kempin, B Koziner, A Middleton, S Jhanwar, R Chaganti, B Clarkson
Journal: Journal of Clinical Oncology (1983)

Twenty-eight patients with Philadelphia chromosome (Ph1)--positive and terminal transferase (TdT)--positive acute leukemia (AL) were treated with intensive chemotherapy used for adult acute lymphoblastic leukemia (L-10 and L-10M protocols). Fifteen patients had a documented chronic phase of Ph1-positive chronic myelogenous leukemia preceding the acute transformation (TdT + BLCML) while the remaining 13 patients did not (TdT + Ph1 + AL). An overall complete remission (CR) rate of 71% was obtained with a median survival of 13 months in the responders. Clinical presentation, laboratory data, cytogenetics, response to treatment, and survivals of the two groups of patients are compared. These results appear to be similar, suggesting a common or closely related origin. Since the overall survival of those receiving chemotherapy maintenance is poor, three patients underwent allogeneic bone marrow transplantation (BMT) from histocompatibility leukocyte antigen--matched siblings after they achieved CR. One of them is a long-term survivor (35 + months) with a Ph1-negative bone marrow. New techniques such as BMT should be considered in young patients with a histocompatibility leukocyte antigen--compatible sibling once a CR has been achieved.
Strategies for Optimizing the Clinical Impact of Immunotherapeutic Agents Such as Sipuleucel-T in Prostate Cancer
Authors: Ravi A. Madan, Thomas Schwaab, James L. Gulley
Journal: Journal of the National Comprehensive Cancer Network (2012)

Sipuleucel-T is a therapeutic cancer vaccine that has shown improved survival in men with metastatic castration-resistant prostate cancer. As a first-in-class agent, it has been met with both fan-fare and controversy. A broad review of immune-based therapies may reveal the delayed clinical impact of sipuleucel-T to be a class effect. As new strategies of immune-based therapy are developed, their effects can be optimized through better understanding of how they affect disease differently from more standard therapeutics. Furthermore, combination therapy with agents that can either work synergistically with immune-activating therapies or deplete immune-regulating cells may result in more vigorous immune responses and improved clinical outcomes. In addition, therapeutic vaccines may be ideal candidates to safely combine with standard-of-care therapies because of their nonoverlapping toxicity profile. The ultimate role of immunotherapy may not be to supplant standard therapies, but rather to work in concert with them to maximize clinical benefit for patients.
Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial
Authors: Christopher Koh, Laetitia Canini, Harel Dahari, Xiongce Zhao, Susan L Uprichard, Vanessa Haynes-Williams, Mark A Winters, Gitanjali Subramanya, Stewart L Cooper, Peter Pinto, Erin F Wolff, Rachel Bishop, Ma Ai Thanda Han, Scott J Cotler, David E Kleiner, Onur Keskin, Ramazan Idilman, Cihan Yurdaydin, Jeffrey S Glenn, Theo Heller
Journal: The Lancet Infectious Diseases (2015)
The protein expression of Tetratricopeptide Repeat Domain 9 at different stages of mammary development
Authors: smeeta shrestha, Shenglan Cao, Valerie Lin
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

B49 

We have previously reported that tetratricopeptide repeat protein 9 (TTC9) was a progesterone-regulated gene in progesterone receptor (PR)-transfected breast cancer cells MDA-MB-231 and it is also a growth factor-inducible protein. Our results also suggested that TTC9 was a direct PR target gene and was seen to be significantly over expressed in breast cancer tissue compared to normal adjacent tissue. In this study we elucidated the expression profile of TTC9 at various stages of mammary development in female mice. Mammary tissues at pregnant day 10 expressed higher levels of TTC9 in comparison to virgin mice and mice at pregnant day 18 when the mammary gland had already started secretory differentiation. Early lactating mammary gland (day 2 post partum) expressed similar levels of TTC9 protein to that at pregnant day 18. There is a gradual increase in TTC9 level as lactation proceeds through and very high level is attained by lactating day 18. Mammary gland undergoing involution also expressed high level of TTC9 protein comparable to that at lactating 18. Interestingly, forced weaning after day 12 lactation caused a sharp rise of TTC9 protein level. Restoration of lactation by replacing the pups again caused a reduction of TTC9 level in the mammary gland. We hypothesized that TTC9 may be involved in mammary tissue remodeling. This is supported by the studies using teat sealing model in which normal lactating gland express considerably lower levels of TTC9 then the teat-sealed glands in the same mice. In conclusion, the protein level of TTC9 is regulated as a function of mammary development. TTC9 expression is negatively associated with secretory state but positively related to mammary involution when the cells undergo apoptosis. The findings provide clues to further elucidate the role of TTC9 in mammary development and its possible involvement in breast cancer.
CT-guided biopsy of lung lesions: Experience of an oncology center in Brazil
Authors: Anna Morais, MariaCecilia Maiorano, Juliana Puka, Caio Fernandes, Frederico Fernandes, Gustavo Prado, Teresa Takagaki
Journal: European Respiratory Journal (2012)

Introduction : Computed tomography (CT) guided lung biopsy is widely accepted as an effective and safe diagnostic procedure for accessing thoracic lesions. Aims : To present the experience of an oncology center in Brazil in the use of CT-guided lung biopsy and describe its effectiveness and complications. Materials and methods : A retrospective analysis of medical records from outpatients attending routine consultations at Pulmonary Division of Sao Paulo State Cancer Institute (Sao Paulo, Brazil), who underwent transthoracic biopsy between December 2010 and November 2011 was conducted. Descriptive analysis of patients' characteristics, lesions' aspects, procedure techniques, diagnostic yield and complications was performed. Subgroup analysis was carried out to access differences between complicated and non-complicated procedures. Predictors of complications identified in univariate analysis were submitted to logistic regression to explore their significance as independent risk factors. Results : 71 subjects were submitted to CT-guided lung biopsy. Results were diagnostic in 60 cases (84.5%). Lesions were malignant in 55 (91.6%) and benign in 4 cases. Overall complication rate was 22% and included 14 pneumothorax (19.7%) and 2 hemothorax (2.8%). Chest drainage was necessary in 4 cases (5.6%). A statistically significant correlation was found between lesion diameter and complication. Smaller lesions were associated with higher rates of complications (OR 9.82, for first quartile vs others). Conclusions: CT-guided lung biopsy resulted in a high diagnostic yield with an acceptable rate of non-severe complications, being pneumothorax the most frequent. Small lesions were more prone to complicate.
Multiplicity of Cell Response to the BAI Strain A (Myeloblastosis) Avian Tumor Virus. VII. Elaboration of Virus by Non-neoplastic Hepatic Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hideo Ishiguro, Dorothy Beard, J. W. Beard
Journal: JNCI Journal of the National Cancer Institute (1963)

Journal Article Multiplicity of Cell Response to the BAI Strain A (Myeloblastosis) Avian Tumor Virus. VII. Elaboration of Virus by Non-neoplastic Hepatic Cells Get access Guy de Thé, Guy de Thé Department of Surgery, Duke University Medical Center, Durham, North Carolina Search for other works by this author on: Oxford Academic PubMed Google Scholar Hideo Ishiguro, Hideo Ishiguro Department of Surgery, Duke University Medical Center, Durham, North Carolina Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothy Beard, Dorothy Beard Department of Surgery, Duke University Medical Center, Durham, North Carolina Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Beard J. W. Beard Department of Surgery, Duke University Medical Center, Durham, North Carolina Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 31, Issue 3, September 1963, Pages 717–729, https://doi.org/10.1093/jnci/31.3.717 Published: 01 September 1963 Article history Received: 15 April 1963 Published: 01 September 1963
Control of allergic rhinitis and asthma test, asthma control test and FeNO in asthma
Authors: Raquel Melo, Daniela Alves, Joao Cruz, Miguel Guimarães, Ricardo Lima
Journal: European Respiratory Journal (2012)

Introduction : The assessment of asthma control is essential in the follow-up of this disease.   Objectives :Assessment of asthma and/or rhinitis control through the application of two questionnaires and the measurement of Fractional Nitric Oxide concentration in exhaled breath (FeNO).   Methods:  Cross-sectional observational study of patients with asthma and/or rhinitis that, in a two months period, visited a respiratory function laboratory to perform lung functional tests with measurement of FeNO and to whom were applied 2 questionnaires: Control of Allergic Rhinitis and Asthma Test (CARAT) and Asthma Control Test (ACT).   Results:  109 patients, 65,7% women, mean age 32,6±17,9years. Of these, 63,3% had asthma and rhinitis, 24,8% had asthma and 11,9% had rhinitis. The mean FeNO was 36±28,4ppb (min/max= 4/115). 58,7% patients were atopic and a statistically significant association was established between atopy and FeNO (p   Conclusions:  There was a statistically significant association between: atopy/positive bronchodilatation test and higher FeNO, and between CARATt/CARATa and ACT test scores. This study highlights the importance of using low cost and easily applicable questionnaires that are validated in the assessment of asthma control.
Mitochondrial DNA sequences and multiple data sets: a phylogenetic study of phytophagous beetles (Chrysomelidae: Ophraella).
Authors: D J Funk, D J Futuyma, G Ortí, A Meyer
Journal: Molecular Biology and Evolution (1995)

This paper presents the phylogenetic infrastructure for an integrated historical and experimental study of host use evolution in the chrysomelid leaf beetle genus Ophraella. We report the collection of sequence data from the 16S ribosomal RNA (446 bp) and the cytochrome oxidase subunit I (420 bp) mitochondrial genes from 12 species of Ophraella and two outgroups. Sequence analysis revealed a strong A + T nucleotide bias, high interspecific COI sequence divergences (up to 21.4%) that greatly exceeded those for 16S (up to 5.9%), high intraspecific COI divergences (up to 3.8%), a dearth of amino acid substitutions in COI, and differing substitution patterns in ribosomal stems and loops. Intraspecific variation in COI haplotypes generally supported the genealogical coherence of Ophraella lineages, while suggesting two cases of paraphyletic species. Separate phylogenetic analyses of 16S and COI data sets yielded largely congruent trees. A combined 16S + COI analysis yielded a single shortest tree under maximum parsimony that was identical to trees provided by successive approximations, neighbor-joining, and maximum-likelihood methods. This topology proved robust to various forms of weighting and most nodes were highly supported (by bootstrap analysis). Separate parsimony analyses of mtDNA and previously collected morphological and electromorphic data sets revealed congruent estimates of all cladistic relationships except those within one clade. Analysis of the pooled data sets in a combined approach additionally provided support for the basal placement of two species from this clade, although the topology for the remaining species was weakly supported and incongruent with the mtDNA tree. Each data set contained significantly structured phylogenetic signal with respect to this clade, and data sets exhibited limited conflict (character incongruence) with each other. The combined data set, however, was found to lack phylogenetic signal. These observations may imply that pooling heterogeneously evolving classes of data obscured the phylogenetic signal in each, a potential limitation of the combined approach.
AutoCPAP devices accurately identify obstructive sleep apnea patients with residual apnea during treatment
Authors: Lena Hess, Tsogyal D. Latshang, Malcolm Kohler, Christian M. Lo Cascio, Robert Thurnheer, Konrad E. Bloch
Journal: European Respiratory Journal (2011)

Background: Objective data on the effectiveness of CPAP therapy of patients with obstructive sleep apnea syndrome (OSA) are needed. The accuracy of the apnea/hypopnea index (AHI) recorded by CPAP devices during treatment is unknown. We tested the hypothesis that AHI derived from CPAP devices accurately predict an elevated AHI during a sleep study.

Methods: 48 OSA patients, mean±SD age 54±6y, baseline AHI 52.5±21.6/h, underwent in-laboratory sleep studies once or twice during long-term autoCPAP therapy. AHI from CPAP devices (ResMed S8, Philips Respironics REMstar) during sleep studies and during the preceeding 7 nights were recorded.

Results: The AHI derived from 60 sleep studies was 5.0±6.2/h. The mean difference (bias) of the corresponding AHI from CPAP devices was 1.8/h, 95% confidence interval -7.4 to +11.0/h. The difference between the minimal and maximal CPAP-derived AHI in the week preceeding the sleep study was 6.1±5.1/h. In 22 of 60 sleep studies, the AHI was >5/h. The accuracy of the AHI from CPAP devices to correctly predict an elevated AHI >5/h was quantified by the area under the receiver operating characteristic curve of 0.87 (95% CI 0.78 to 0.96). The sensitivity and specificity of an AHI >5/h from CPAP devices to identify a polygraphic AHI >5/h were 86% and 75%, respectively; the negative and positive predictive values were 93% and 56%, respectively.

Conclusions: The studied CPAP devices accurately identify OSA patients with elevated AHI during treatment. Because of the high night-to-night variability mean AHI derived from autoCPAP devices over several nights might be clinically more relevant than a single night AHI measured in the sleep laboratory.
Minimally Invasive Approaches to Rectal Cancer and Diverticulitis
Authors: Scott A. Strong, Nathaniel J. Soper
Journal: JAMA (2015)

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