tbuckley/cabot-search huggingface dataset:
Trade-offs between the accuracy and integrity of autobiographical narrative in memory reconsolidation
Authors: Carlos Montemayor
Journal: Behavioral and Brain Sciences (2015)

Abstract Lane et al. propose an integrative model for the reconsolidation of traces in their timely and impressive article. This commentary draws attention to trade-offs between accuracy and self-narrative integrity in the model. The trade-offs concern the sense of agency in memory and its role in both implicit and explicit memory reconsolidation, rather than balances concerning degrees of emotional arousal.
Redistribution of the nuclear protein IFI16 into the cytoplasm of ultraviolet B-exposed keratinocytes as a mechanism of autoantigen processing
Authors: S. Costa, C. Borgogna, M. Mondini, M. De Andrea, P.L. Meroni, E. Berti, M. Gariglio, S. Landolfo
Journal: British Journal of Dermatology (2010)

The skin has long been recognized as a prominent target tissue in systemic lupus erythematosus (SLE) which plays a crucial role in the initiation and perpetuation of the autoimmune reaction cascade as a consequence of ultraviolet (UV)-induced keratinocyte apoptosis. Antibodies against IFI16 (interferon-inducible protein 16) have been detected in the sera of patients with SLE.To verify whether the induction of autoimmunity against IFI16 involves redistribution of this nuclear protein in keratinocytes during UVB-induced cell death.An in vitro epidermal model was developed to investigate the fate of the IFI16 protein in keratinocytes after irradiation with UVB; both keratinocyte monolayers and human skin explants were used. IFI16 expression and localization were also analysed in diseased skin sections of patients with SLE.We demonstrated that IFI16, normally restricted to the nucleus, can be induced to appear in the cytoplasm under conditions of UVB-induced cell injury. This nucleus to cytoplasm translocation was also observed in skin explants exposed to UVB and in the diseased skin sections from patients with SLE. In addition, IFI16 was found in the supernatants of UVB-exposed keratinocytes.The finding that IFI16 is present in the cytoplasm of diseased skin cells from patients with SLE and the demonstration of IFI16 in the supernatants of UVB-exposed keratinocytes, suggest that UVB irradiation or other stimuli may favour an abnormal IFI16 presentation to the afferent limb of the immune system and potentially an autoimmune response against the protein itself.
Echocardiographic findings in severe chronic obstructive pulmonary disease (COPD) patients who desaturate during 6-minute walking test (6MWT)
Authors: Juan Antonio Mazzei, Alejandro Raimondi, Carlos Gustavo Di Bartolo, Analía Barro, Jorge Lerman, Oscar Grosso
Journal: European Respiratory Journal (2011)

Objective:  To study the relationship between clinical, functional and echocardiographic findings in severe COPD patients who desaturate during 6MWT.   Methods:  18 GOLD 3-4 patients who desaturated during 6MWT (SpO2   Results:  Eight female and 10 male were studied, mean age 61.8±8 yrs, mean BMI was 24.75 (5) kg/m 2 , mean FVC was 2.85±0.8, mean DLCO 45.5% (range=31-94), mean walked distance 315 m (range=120-480), the mean systolic PAP was 32.25±8.68 mmHg and 16/18 presented systolic PAP hypertension.  Mean systolic PAP was 26.12 mmHg in 8 patients with BODE 2-4 and 37.37 mmHg in 10 patients with BODE 5 (p=0.0312).  No significant association between systolic PAP and GOLD, FVC, MEP, MIP, DLCO, Tei Index, or basal SpO2 were observed.  There was no significant association between 6MW distance and systolic PAP (r=-0.41; p=0.08) or between DLCO and O2 saturation in the first minute walk (r=0.39; p=0.08).   Conclusions:  We found a significant association between systolic PAP and BODE.  Trends without significant association among systolic PAP and 6MW walked distance and DLCO with SpO2 in the first minute were observed.  Further studies are needed
Beta2 adrenergic agonist attenuates house dust mite-induced allergic airway inflammation in mice
Authors: Go Kato, Koichiro Takahashi, Hiroki Tashiro, Shinichiro Hayashi
Journal: European Respiratory Journal (2014)

Background  Long acting beta2 adrenergic agonist (LABA) is commonly used combination with inhaled corticosteroid (ICS) in asthmatic patients. Previous reports suggested that LABA have anti-inflammatory effect to airway inflammation. However, little is known that mechanisms of anti-inflammatory effect of LABA. The aim of this study was to clarify whether LABA can inhibit allergic airway inflammation in vivo, and mechanisms of LABA effect in vitro.  Methods  Balb/c mice were sensitized and challenged to house dust mite (HDM). The effect of formoterol (FORM) treatment in HDM-induced murine airway inflammation was assessed using these models by inflammatory cells, cytokines, and histological findings. Bone marrow derived dendritic cells (BMDCs) were stimulated with HDM in vitro to evaluate cytokine production.  Results  FORM decreased the number of eosinophils (HDM 2.8 ± 1.6 v.s. HDM+FORM 0.5 ± 0.6 × 10 4  / ml, p 4  / ml, p  Conclusion  These data indicate that LABA inhibit Th2 and Th17 cytokines production and neutrophils and eosinophils in airways. Inhibitory effects of LABA in DCs suggested that DCs might be attenuated HDM-induced airway inflammation.
Exercise respiratory cycle time components in patients with emphysema
Authors: Alessandro Maria Ferrazza, Patrizia Paoletti, Gabriele Valli, Paolo Onorati, Dario Martolini, Michela Mordenti, Francesco Vaccaro, Paolo Palange
Journal: European Respiratory Journal (2012)

Background. We have recently demonstrated that in patients with COPD the severity of emphysema (E) measured by high resolution computed tomography (HRCT) correlated with: ratio VTpeak/FEV1; VE/VCO2 slope and PETCO2 values at peak exercise. The aim of this study was to further investigate if exercise respiratory cycle time components correlated with % of E measured by HRCT. Method. Twelve patients (age = 65 ± 8 yrs; FEV1 = 55 ± 17%pred) with moderate to severe E (quantified by lung HRCT as % voxels   Moreover, by dividing the patients in two groups based on the % of E (>50% and
Kinetics of dyspnea during 6-minute walking test in obese patients with obstructive sleep apnea (OSA)
Authors: R. Rusca Mestre, M. Croteau, B. Wuyam, R. Tamisier, A. Grangier, S. Gorain, P. Levy, F. Maltais, J.L. Pépin, I. Vivodtzev
Journal: European Respiratory Journal (2013)

Background: Dyspnea during walk is usually observed in Obesity and OSA patients but its mechanism is not clearly established. We investigated the kinetics of dyspnea during six-minute walking test and physiological correlates.

Methods: 20 obese CPAP-treated OSA (BMI= 38 ± 4 kg/m²) performed a six-minute walking test (6MWT) and measurements of pulmonary function, fat-free-mass, physical activity, quadriceps and respiratory muscle strength, Sadoul scale and maximal aerobic capacity on cycloergometer. Dyspnea was assessed every two minutes during the 6MWT using the modified Borg scale to evaluate its kinetic of improvement during walk. The median of delta of dyspnea at 2-min walk was used to distinguish patients with early dyspnea (Borg score > 2: n = 8) to those with late dyspnea (Borg score ≤ 2: n = 12).

Results : We found significantly distinct profiles of kinetics of dyspnea during the 6MWT (ANOVA: p < 0.001; fig.1). Leg discomfort at 2-min walk (4.0(2.3-6.0) vs. 1.9(0.0-2.0), p = 0.003) and Sadoul score (3.0(2.0-4.25) vs. 1.5(1.0-2.0), p = 0.026) vs. were significantly higher in patients with early dyspnea as compared with late dyspnea group, respectively. None of the other physiological parameters were different between groups.

Conclusion : Obese OSA presented with two different profiles of dyspnea scores during 6MWT which were concomitant to leg discomfort during walk and perception of dyspnea during daily task.

![Figure][1]  [1]: pending:yes
Involvement of coactivator associated arginine methyltransferase 1 (CARM1) in development of elastase-induced progressive emphysema
Authors: Rim S.J. Sarker, Alexander Bohla, Gerrit John, Katrin Kohse, Oana Veronica Amarie, MarK T. Bedford, Oliver Eickelberg, Ali Önder Yildirim
Journal: European Respiratory Journal (2013)

Chronic obstructive pulmonary disease comprises chronic bronchitis and emphysema. Emphysema is characterized by destruction of alveolar walls leading to enlarged air spaces and reduced surface area. CARM1-an arginine methyltransferase and a coactivator to regulate transcription, translation and DNA repair is found important for regulating proliferation and differentiation of pulmonary epithelial cells (O’Brien, 2010). We wanted to investigate its role in emphysema development and progression.  Porcine pancreatic elastase (PPE) was applied to C57BL/6 mice. Lung function, histology and gene expression were analyzed on day 2, 28, 56, and 161. CARM1+/- mice were analyzed on day 28. LA-4 alveolar cells were treated with CARM1 siRNA. Proliferative, apoptotic characteristics were measured by gene expression or wound healing assays.  PPE-treated wild-type mice showed significant increased forced residual capacity, total lung capacity, dynamic lung compliance and decreased Tiffeneau index correlated to increased mean linear chord length (Lm) in a time dependent manner. qRT-PCR showed decreased proliferation (Cyclin D1) and increased apoptosis marker (Bax) in lung. CARM1 expression was significantly diminished. PPE-treated CARM1+/- mice displayed impaired lung function and enhanced Lm compared to wild type. Furthermore, silencing of CARM1 by siRNA in LA-4 cells led to reduced migration and proliferation.  PPE treated wild type mice developed progressive emphysema and impaired lung function during 161 days of analysis. CARM1+/- mice showed to be more susceptible to emphysema progression. Pharmacological implication of CARM1 could be a prospectus therapy for COPD.
Genetic properties of the MAGIC maize population: a new platform for high definition QTL mapping in Zea mays
Authors: Matteo Dell’Acqua, Daniel M. Gatti, Giorgio Pea, Federica Cattonaro, Frederik Coppens, Gabriele Magris, Aye L. Hlaing, Htay H. Aung, Hilde Nelissen, Joke Baute, Elisabetta Frascaroli, Gary A. Churchill, Dirk Inzé, Michele Morgante, Mario Enrico Pè
Journal: Genome biology (2015)

Maize (Zea mays) is a globally produced crop with broad genetic and phenotypic variation. New tools that improve our understanding of the genetic basis of quantitative traits are needed to guide predictive crop breeding. We have produced the first balanced multi-parental population in maize, a tool that provides high diversity and dense recombination events to allow routine quantitative trait loci (QTL) mapping in maize. We produced 1,636 MAGIC maize recombinant inbred lines derived from eight genetically diverse founder lines. The characterization of 529 MAGIC maize lines shows that the population is a balanced, evenly differentiated mosaic of the eight founders, with mapping power and resolution strengthened by high minor allele frequencies and a fast decay of linkage disequilibrium. We show how MAGIC maize may find strong candidate genes by incorporating genome sequencing and transcriptomics data. We discuss three QTL for grain yield and three for flowering time, reporting candidate genes. Power simulations show that subsets of MAGIC maize might achieve high-power and high-definition QTL mapping. We demonstrate MAGIC maize's value in identifying the genetic bases of complex traits of agronomic relevance. The design of MAGIC maize allows the accumulation of sequencing and transcriptomics layers to guide the identification of candidate genes for a number of maize traits at different developmental stages. The characterization of the full MAGIC maize population will lead to higher power and definition in QTL mapping, and lay the basis for improved understanding of maize phenotypes, heterosis included. MAGIC maize is available to researchers.
Antiemetic Studies on the NK1 Receptor Antagonist Aprepitant
Authors: John P. Stoutenburg, Harry Raftopoulos
Journal: Journal of the National Comprehensive Cancer Network (2004)

Aprepitant (Emend, Merck Inc., Whitehouse Station, NJ), a neurokin-1 (NK1) receptor antagonist, is a first-in-class agent approved for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). It competitively binds to NK1 receptors, blocks the binding of substance P, the natural ligand, and prevents signal transduction. Early clinical trials showed that aprepitant combined with standard therapy (corticosteroids and serotonin receptor antagonists) provided improved antiemetic protection in patients receiving highly emetogenic chemotherapy. The results of three randomized, double blind, placebo-controlled trialsthat compared aprepitant plus standard therapy with standard therapy plus placebo showed significant improvements in complete response rates (defined as no emesis and no use of rescue medication) with the addition of aprepitant (58.8% to 71% vs. 43.3% to 52.3%; P < .05 for all). Benefits were found in the acute phases, delayed phases, and in the overall study periods. Multiple secondary endpoints also favored the addition of aprepitant, particularly in the delayed phases and overall study periods. In extended trials in which treatment was continued for up to 6 cycles of highly emetogenic chemotherapy, the antiemetic effect was maintained and remained statistically greater for the aprepitant plus standard therapy group compared with standard therapy and placebo. The addition of aprepitant was well tolerated, and common adverse events were similar to those seen with standard therapy plus placebo. A clinically significant drug interaction with CYP3A4-metabolized cytotoxic agents was reported in one trial, but not confirmed in the others. The additional protection confirmed by aprepitant translated into a decreased impact of CINV on patients' daily lives as measured by the Functional Living Index-Emesis questionnaire. Aprepitant adds additional antiemetic protection to standard therapy and should be considered in all patients receiving highly emetogenic chemotherapy.
Leukotriene receptor antagonism prevents lung protein leakage and hypoxaemia in a septic cat model
Authors: KM Schutzer, A Larsson, B Risberg, A Falk
Journal: European Respiratory Journal (1994)

Products of the arachidonic acid cascade have been found to play an important role in the pathophysiology in experimental shock and in ARDS. The effect of cysteinyl-leukotriene (cLT) blockade on the development of respiratory failure during septic shock was examined. Ventilated cats received an infusion of Escherichia coli bacteria. Pretreatment was given with diethylcarbamazine (DEC), a leukotriene synthetase inhibitor, or a new potent cLT receptor antagonist, ICI 198,615. With a gamma camera, the distributions of plasmatransferrin radiolabelled with indium-113m chloride (113mIn) and erythrocytes radiolabelled with technetium-99m (99mTc) were measured over the lungs. A normalized slope index (NSI) reflecting protein leakage, based on the transferrin extravasation, was calculated. In the nonseptic control group (n = 7) NSI was 4.4 x 10(-4) +/- 0.7 x 10(-4).min-1 (mean +/- SEM). Unpretreated septic animals (n = 7) showed a protein leakage after bacterial infusion, with a NSI of 34 +/- 3.5 x 10(-4).min-1. Pretreatment with DEC (n = 6) significantly reduced NSI to 16 +/- 1.5 x 10(-4).min-1. In the group pretreated with ICI 198,615 (n = 8), NSI was 9 +/- 1.2 x 10(-4).min-1. Arterial oxygen tension (PaO2) remained at baseline level of 20 +/- 1.0 kPa during the experimental period in both the nonseptic control group and the ICI 198,615 pretreated group. In the unpretreated septic group, PaO2 fell progressively from a preseptic value of 21 +/- 0.9 to 12 +/- 1.5 kPa after 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Total IgE relationship with genetic markers and smoking factor in patients with COPD
Authors: Naima Ubaydullaeva
Journal: European Respiratory Journal (2014)

Smoking is a major risk factor for COPD, and nicotine promotes the development of allergic reactions. Numerous studies have shown that among smokers and their families we can identify people with a high content of immunoglobulin E.  Aim: To determine the level of total immunoglobulin E (Ig E) in conjunction with genetic markers and smoking in patients with chronic obstructive pulmonary disease (COPD).  Methods: We investigated 50 COPD patients (age 50.1±2.2 years), and the control group consisted of 20 healthy volunteers. The level of total Ig E were determined in serum by ELISA. ABO blood group system, Rh were adjusted by direct hemagglutination on the tablet.  Results: Values of total Ig E COPD among smokers marked slightly higher than in non-smokers. The women showed a trend toward increased levels of Ig E compared with men. Significantly higher levels of Ig E were observed in male smokers with COPD compared with nonsmokers. Increasing of total Ig E was frequently observed in patients with III (B) (23,9%) and II (A) blood groups (26 %), whereas in the presence of IV (AB) group normal blood levels of total Ig E were determined. Patients with blood group II (A) had higher values of Ig E in comparison to other blood groups holders (by 16.8%, p  Conclusion: The elevated total Ig E is a risk factor associated with COPD and II (A) blood group, suggesting genetically caused increased its synthesis in this category of patients.
The efficacy of mesna (2-mercaptoethane sodium sulfonate) as a uroprotectant in patients with hemorrhagic cystitis receiving further oxazaphosphorine chemotherapy.
Authors: G L Andriole, J T Sandlund, J S Miser, V Arasi, M Linehan, I T Magrath
Journal: Journal of Clinical Oncology (1987)

We examined the possibility of continuing oxazaphosphorine therapy in patients with previously documented cyclophosphamide- or ifosfamide-induced hematuria by concomitant use of the uroprotective agent, mesna. Twenty-six patients with oxazaphosphorine-induced hematuria received additional cyclophosphamide or ifosfamide with mesna. Twelve, who had previously experienced hematuria with ifosfamide, received a median of 3.5 more cycles of ifosfamide/mesna. One patient developed further hematuria (grade 1). Of seven patients who experienced acute hematuria with cyclophosphamide, one experienced further hematuria after an additional course of cyclophosphamide with mesna, but none of the other six patients developed further hematuria when administered either cyclophosphamide/mesna (two) or ifosfamide/mesna (four). Seven patients who had chronic cyclophosphamide-induced hematuria had further oxazaphosphorine with mesna without worsening of their hematuria. Mesna is an effective uroprotective agent that prevents recurrent acute hemorrhagic cystitis, or worsening of chronic hemorrhagic cystitis, in patients receiving further oxazaphosphorine after previous ifosfamide- or cyclophosphamide-induced hematuria.
Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [<sup>11</sup>C]PBR28 PET Brain Imaging Study
Authors: Peter S. Bloomfield, Sudhakar Selvaraj, Mattia Veronese, Gaia Rizzo, Alessandra Bertoldo, David R. Owen, Michael A.P. Bloomfield, Ilaria Bonoldi, Nicola Kalk, Federico Turkheimer, Philip McGuire, Vincenzo de Paola, Oliver D. Howes
Journal: American Journal of Psychiatry (2015)

Objective: The purpose of this study was to determine whether microglial activity, measured using translocator-protein positron emission tomography (PET) imaging, is increased in unmedicated persons presenting with subclinical symptoms indicating that they are at ultra high risk of psychosis and to determine whether microglial activity is elevated in schizophrenia after controlling for a translocator-specific genetic polymorphism. Method: The authors used the second-generation radioligand [11C]PBR28 and PET to image microglial activity in the brains of participants at ultra high risk for psychosis. Participants were recruited from early intervention centers. The authors also imaged a cohort of patients with schizophrenia and matched healthy subjects for comparison. In total, 56 individuals completed the study. At screening, participants were genotyped to account for the rs6971 polymorphism in the gene encoding the 18Kd translocator protein. The main outcome measure was total gray matter [11C]PBR28 binding ratio, representing microglial activity. Results: [11C]PBR28 binding ratio in gray matter was elevated in ultra-high-risk participants compared with matched comparison subjects (Cohen’s d >1.2) and was positively correlated with symptom severity (r=0.730). Patients with schizophrenia also demonstrated elevated microglial activity relative to matched comparison subjects (Cohen’s d >1.7). Conclusions: Microglial activity is elevated in patients with schizophrenia and in persons with subclinical symptoms who are at ultra high risk of psychosis and is related to at-risk symptom severity. These findings suggest that neuroinflammation is linked to the risk of psychosis and related disorders, as well as the expression of subclinical symptoms.
Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.
Authors: C Frostell, M D Fratacci, J C Wain, R Jones, W M Zapol
Journal: Circulation (1991)

Background. The gas nitric oxide (NO) is an important endothelium-derived relaxing factor, inactivated by rapid combination with heme in hemoglobin. Methods and Results. Awake spontaneously breathing lambs inhaled 5-80 ppm NO with an acutely constricted pulmonary circulation due to either infusion of the stable thromboxane endoperoxide analogue U46619 or breathing a hypoxic gas mixture. Within 3 minutes after adding 40 ppm NO or more to inspired gas, pulmonary hypertension was reversed. Systemic vasodilation did not occur. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. During U46619 infusion pulmonary vasodilation was maintained up to 1 hour without tolerance. In the normal lamb, NO inhalation produced no hemodynamic changes. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels nor modify lung histology compared with control lambs. Conclusions. Low dose inhaled NO (5-80 ppm) is a selective pulmonary vasodilator reversing both hypoxia- and thromboxane-induced pulmonary hypertension in the awake lamb [corrected].
T-cell dominated inflammatory reactions in the bronchi of asthmatics are not reflected in matched bronchoalveolar lavage specimens
Authors: LW Poulter, A Norris, C Power, A Condez, B Schmekel, C Burke
Journal: European Respiratory Journal (1992)

Samples of bronchoalveolar lavage (BAL) and endobronchial biopsies were obtained from five patients with clinically diagnosed asthma (ATS criteria). A comparison was made of the presence and distribution of immunocompetent lymphocytes and macrophages within each sample. Significantly raised numbers of T lymphocytes, CD45RO+ lymphocytes, RFD1+ macrophage-like cells and RFD7+ macrophages were seen in the bronchial biopsies. In contrast four out of five of the BAL specimens showed a normal differential cell count, the one exception being a patient exhibiting a degree of lymphocytosis. Further, immunocytological investigation demonstrated a normal distribution of T-cell subsets and macrophage subsets in asthmatic BAL with the exception that in four out of five of these patients a raised number of macrophage-like cells exhibiting phenotypic markers of monocytes was observed. Correlation between BAL and biopsy data was seen in the number of CD45RO+ T-cells present. No other parameters exhibited a significant correlation. Raised expression of HLA-DR was recorded in all asthmatic biopsies, yet lavage cells from the same patients failed to exhibit any increase of HLA-DR density over normal. It is concluded that the immune-associated inflammation present in endobronchial biopsies of clinically stable asthmatics is not reflected in bronchoalveolar lavage samples taken from the same patients.