tbuckley/cabot-search huggingface dataset:
Abnormal Ventilatory Response to Exercise in Adults With Congenital Heart Disease Relates to Cyanosis and Predicts Survival
Authors: Konstantinos Dimopoulos, Darlington O. Okonko, Gerhard-Paul Diller, Craig S. Broberg, Tushar V. Salukhe, Sonya V. Babu-Narayan, Wei Li, Anselm Uebing, Stephanie Bayne, Roland Wensel, Massimo F. Piepoli, Philip A. Poole-Wilson, Darrel P. Francis, Michael A. Gatzoulis
Journal: Circulation (2006)

Background— Limited data exist with which to stratify risk in adult congenital heart disease (ACHD). An increased ventilatory response to exercise, expressed as ventilation per unit of carbon dioxide production (V̇ e /V̇ co 2 slope), is an established predictor of impaired survival in acquired heart disease. We sought to establish the distribution, relation to cyanosis, and prognostic value of the V̇ e /V̇ co 2 slope across a wide spectrum of ACHD patients. Methods and Results— Five hundred sixty ACHD patients of varying diagnoses and 50 healthy controls underwent cardiopulmonary exercise testing at a single laboratory between 2001 and 2004. Patient age was 33.2±12.9 years (mean±SD). Peak oxygen consumption was 23.5±9.0 mL · kg −1 · min −1 . V̇ e /V̇ co 2 slope for all patients was 36.3±15.3. The slope was raised in all ACHD groups compared with controls and was 73% higher in cyanotic patients. Cyanosis, with or without pulmonary arterial hypertension, was the strongest predictor of abnormal V̇ e /V̇ co 2 slope. The V̇ e /V̇ co 2 slope was the most powerful univariate predictor of mortality in the noncyanotic group and the only independent predictor of mortality among exercise parameters on multivariate analysis. In cyanotic patients, no parameter was predictive of death. Conclusions— Ventilatory response to exercise is abnormal across the spectrum of ACHD. Cyanosis is a powerful stimulus for such exaggerated ventilatory patterns irrespective of the presence of pulmonary arterial hypertension. Increased V̇ e /V̇ co 2 slope is the strongest exercise predictor of death in noncyanotic ACHD patients.
How well do questionnaires capture symptomatic relief and well-being over time with NIV in motor neurone disease?
Authors: Hikari Ando, Biswajit Chakrabarti, Carolyn Young, Rosanna Cousins, Everard Thornton, Robert Angus
Journal: European Respiratory Journal (2012)

Benefits of non-invasive ventilation (NIV) in motor neurone disease (MND/ALS) have been explored using quantitative health measurements with little examination of subjective experience. This study explored whether current quantitative tools commonly used in MND adequately capture the effects of NIV. 6 patients (all male, mean age= 67) from an original cohort of 35 were available for the present study having survived a year on NIV. Both questionnaires and semi-structured interviews were completed at 3 occasions: pre-NIV (Point A), 4-6months (Point B) and 10-12months post-NIV (Point C). The scales used were ALSFRS–R (physical functioning), ALSAQ-40 (ALS specific health status), MNDRS (dyspnoea), BDI (depression), BHS (hopelessness), HADS (depression and anxiety), and ESS (sleepiness). During the interviews, experience of NIV, physical changes and their impact on daily life were explored. All interviews were assessed using thematic analysis. Quantitative scores were compared using analysis of variance. Changes were seen from points A to C in ALSFRS-R 33 v 27 (p=0.021), ALSAQ subscale for communication 46 v 29 (p=0.018), BHS 3.67 v 1.80 (p=0.03) and ESS 9.50 v 2.8 (p=0.046). The scores of ALSFRS-R denote worsening functional status, while the other scales indicate improvement. Qualitatively, 4 symptoms were discerned as problematic and were improved by NIV: energy level, quality of night sleep, daytime sleepiness and breathlessness. The results show the multidimensional range of symptoms that relate to hypoventilation in MND and how the routinely employed scales may fail to capture significant symptomatology or the impact of NIV on such symptoms.
Split tolerance induced by the intrathymic adoptive transfer of thymocyte stem cells.
Authors: R P Shimonkevitz, M J Bevan
Journal: The Journal of Experimental Medicine (1988)

The intrathymic transfer of semiallogeneic CD4/CD8 double-negative (DN) thymocyte stem cells into irradiated host mice resulted in a transient state of chimerism in adoptive host thymus, spleen, and lymph nodes. Host-derived T cells, isolated from the thymus and periphery of the chimeric mice, were found to be specifically nonresponsive to the MHC antigens of the semiallogeneic DN donor in cytotoxicity assays. This nonresponsiveness was not permanent, but persisted as long as appreciable numbers of Thy-1 alloantigen-positive progeny of the DN donor cells could be detected in the spleen and lymph nodes of adoptive host mice. FACS sorting of DN donor cells before intrathymic transfer indicated that nonresponsiveness could be induced by Thy-1+ cells and was therefore not attributable to contaminating thymic macrophages, dendritic cells, or B cells. When FACS-sorted Thy-1+ (bm5 x bm12)F1 DN cells were transferred intrathymically into C57BL/6 hosts, nonresponsiveness to DN donor MHC class I but not class II alloantigen (split tolerance) was observed. These experiments were repeated using FACS-sorted Thy-1+ DN donor cells that were semiallogeneic to the irradiated adoptive host at either MHC class I or class II locus with similar results. Limiting dilution analysis showed that host-derived CTL precursors were tolerant of DN donor MHC class I alloantigen and no evidence for the involvement of suppressor T cells was found. The data indicate that murine thymocytes themselves are capable of tolerizing to MHC class I but not class II alloantigen after intrathymic transfer. The implications for intrathymic T cell differentiation and maintenance of self tolerance are discussed.
Lung Cancer and Chronic Obstructive Pulmonary Disease: Needs and Opportunities for Integrated Research
Authors: A. Punturieri, E. Szabo, T. L. Croxton, S. D. Shapiro, S. M. Dubinett
Journal: JNCI Journal of the National Cancer Institute (2009)

Lung cancer and chronic obstructive pulmonary disease (COPD) are leading causes of morbidity and mortality in the United States and worldwide. They share a common environmental risk factor in cigarette smoke exposure and a genetic predisposition represented by the incidence of these diseases in only a fraction of smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. To investigate commonalities in disease mechanisms and perspectives for disease chemoprevention, the National Heart, Lung, and Blood Institute (NHLBI) and the National Cancer Institute (NCI) held a workshop. The participants identified four research objectives: 1) clarify common epidemiological characteristics of lung cancer and COPD; 2) identify shared genetic and epigenetic risk factors; 3) identify and validate biomarkers, molecular signatures, and imaging-derived measurements of each disease; and 4) determine common and disparate pathogenetic mechanisms. These objectives should be reached via four research approaches: 1) identify, publicize, and enable the evaluation and analysis of existing datasets and repositories of biospecimens; 2) obtain phenotypic and outcome data and biospecimens from large studies of subjects with and/or at risk for COPD and lung cancer; 3) develop and use animal and other preclinical models to investigate pathogenetic links between the diseases; and 4) conduct early-phase clinical trials of potential chemopreventive agents. To foster much needed research interactions, two final recommendations were made by the participants: 1) incorporate baseline phenotyping and outcome measures for both diseases in future longitudinal studies of each disease and 2) expand collaborative efforts between the NCI and NHLBI.
Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment
Authors: Hidehiro Yamane, Jinfang Zhu, William E. Paul
Journal: The Journal of Experimental Medicine (2005)

T cell receptor (TCR) signaling plays an important role in early interleukin (IL)-4 production by naive CD4+ T cells. This “antigen-stimulated” early IL-4 is sufficient for in vitro Th2 differentiation. Here, we provide evidence that early IL-4 production by naive CD4+ T cells stimulated with cognate peptide requires TCR-induced early GATA-3 expression and IL-2 receptor signaling, both of which are controlled by the degree of activation of extracellular signal-regulated kinase (ERK). Stimulation of naive CD4+ T cells from TCR transgenic mice with low concentrations of peptide-induced IL-2–dependent STAT5 phosphorylation, IL-4-independent early GATA-3 expression, and IL-4 production. Neutralization of IL-2 abolished early IL-4 production without affecting early GATA-3 expression. In addition, naive CD4+ T cells from GATA-3 conditional KO mice failed to produce early IL-4 in response to TCR/CD28 stimulation. Stimulation with high concentrations of peptide abrogated early GATA-3 expression and IL-2–dependent STAT5 phosphorylation, and resulted in the failure to produce early IL-4. This high concentration–mediated suppression of early IL-4 production was reversed by blockade of the ERK pathway. A MEK inhibition rescued early GATA-3 expression and responsiveness to IL-2; these cells were now capable of producing early IL-4 and undergoing subsequent Th2 differentiation.
Lung Epithelial Cells Are a Major Site of Murine Gammaherpesvirus Persistence
Authors: James P. Stewart, Edward J. Usherwood, Alan Ross, Heather Dyson, Tony Nash
Journal: The Journal of Experimental Medicine (1998)

It is currently believed that latently infected, resting B lymphocytes are central to gammaherpesvirus persistence, whereas mucosal epithelial cells are considered nonessential. We have readdressed the question of nonlymphoid persistence using murine gammaherpesvirus 68 (MHV-68). To dissect lymphoid from nonlymphoid persistence, we used μMT transgenic mice that are defective in B cells. MHV-68 DNA persisted in the lungs of intact and B cell–deficient mice. Both episomal and linear forms of the virus genome were present in lungs, implying the presence of both latency and productive replication. In situ hybridization for virus tRNA transcripts revealed latent MHV-68 in pulmonary epithelial cells. Infectious virus was recovered from the lungs of μMT mice after T cell depletion, showing that the persisting virus DNA was reactivatable. Finally, using adoptive transfer of B cells into B cell–deficient mice, it was shown that virus persisting in lungs seeded splenic B cells, and virus resident in the spleen seeded the lungs. These results show that mucosal epithelia can act as a nonlymphoid reservoir for gammaherpesvirus persistence, and that there is a two-way movement of virus between lymphoid and nonlymphoid compartments during persistence.
Apricoxib, a Novel Inhibitor of COX-2, Markedly Improves Standard Therapy Response in Molecularly Defined Models of Pancreatic Cancer
Authors: Amanda Kirane, Jason E. Toombs, Katherine Ostapoff, Juliet G. Carbon, Sara Zaknoen, Jordan Braunfeld, Roderich E. Schwarz, Francis J. Burrows, Rolf A. Brekken
Journal: Clinical Cancer Research (2012)

Abstract Purpose: COX-2 is expressed highly in pancreatic cancer and implicated in tumor progression. COX-2 inhibition can reduce tumor growth and augment therapy. The precise function of COX-2 in tumors remains poorly understood, but it is implicated in tumor angiogenesis, evasion of apoptosis, and induction of epithelial-to-mesenchymal transition (EMT). Current therapeutic regimens for pancreatic cancer are minimally effective, highlighting the need for novel treatment strategies. Here, we report that apricoxib, a novel COX-2 inhibitor in phase II clinical trials, significantly enhances the efficacy of gemcitabine/erlotinib in preclinical models of pancreatic cancer. Experimental Design: Human pancreatic cell lines were evaluated in vitro and in vivo for response to apricoxib ± standard-of-care therapy (gemcitabine + erlotinib). Tumor tissue underwent posttreatment analysis for cell proliferation, viability, and EMT phenotype. Vascular parameters were also determined. Results: COX-2 inhibition reduced the IC50 of gemcitabine ± erlotinib in six pancreatic cancer cell lines tested in vitro. Furthermore, apricoxib increased the antitumor efficacy of standard combination therapy in several orthotopic xenograft models. In vivo apricoxib combination therapy was only effective at reducing tumor growth and metastasis in tumors with elevated COX-2 activity. In each model examined, treatment with apricoxib resulted in vascular normalization without a decrease in microvessel density and promotion of an epithelial phenotype by tumor cells regardless of basal COX-2 expression. Conclusions: Apricoxib robustly reverses EMT and augments standard therapy without reducing microvessel density and warrants further clinical evaluation in patients with pancreatic cancer. Clin Cancer Res; 18(18); 5031–42. ©2012 AACR.
Implementation of an App-based neuromuscular training programme to prevent ankle sprains: a process evaluation using the RE-AIM Framework
Authors: Ingrid Vriend, Iris Coehoorn, Evert Verhagen
Journal: British Journal of Sports Medicine (2014)

Background/aim The contemporary electronic media is regarded as a practical tool in the dissemination of preventive measures and interventions. For this purpose an App (free of charge) was developed including an efficacious programme for the prevention of ankle sprain recurrences. This study evaluated the implementation effectiveness of this ‘Versterk je Enkel’ App. Methods The App was evaluated within its practical context using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) Framework. The launch of the App was accompanied by a press release, website banners, as well as online and offline advertisements. Data for the evaluation of the App were objectively registered through Google analytics. Data were obtained in February 2013 based on 25 781 users resulting in follow-ups of 18 months (iOS version) and 15 months (Android version), respectively. Users questionnaires provided a qualitative view of the objectively assessed measures (n=82) to gain insight into the demographics of users, reasons to download, user experience and how the information was used. Results The App reached only 2.6% of the projected target population. User ratings for the App's relevancy, clarity, usefulness, appeal, information and reliability were high. App usage indicates that compliance with the embedded programme was low. Conclusions Although the App was well received by the users, targeted efforts are required to ensure proper uptake and usage of the App by the target population. This also holds true for eHealth and mHealth efforts aimed at athlete care and injury prevention in general.
Long-Term Outcomes in Mild/Moderate Chronic Obstructive Pulmonary Disease in the European Community Respiratory Health Survey
Authors: Roberto de Marco, Simone Accordini, Josep M. Antò, Thorarinn Gislason, Joachim Heinrich, Christer Janson, Deborah Jarvis, Nino Künzli, Bénédicte Leynaert, Alessandro Marcon, Jordi Sunyer, Cecilie Svanes, Matthias Wjst, Peter Burney
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Little is known about the long-term outcomes of individuals with mild/moderate chronic obstructive pulmonary disease (COPD) according to spirometric criteria.To test whether nonsmokers and asymptomatic subjects with a spirometric diagnosis of COPD have a steeper decrease in lung function and higher hospitalization rates than subjects without airway obstruction.A total of 5,205 subjects without asthma (20-44 years of age) from the general population, with FEV(1) >or= 50% predicted at baseline, were followed for 9 years in the frame of an international cohort study. Percent decrease in FEV(1) (DeltaFEV(1)%) and the annual hospitalization rate for respiratory causes during the follow-up were assessed for each subject.At baseline, 324 (6.2%) subjects had the prebronchodilator FEV(1)/FVC ratio less than the lower limit of normal (LLN-COPD), and 105 (2.0%) subjects had the same ratio less than 0.70 (modified GOLD-COPD). At follow-up, smokers with LLN-COPD (n = 205) had a greater mean DeltaFEV(1)% (1.7%; 95% confidence interval [CI], 0.8-2.7) and a higher hospitalization rate (rate ratio [RR], 2.52; 95% CI, 1.65-3.86) than normal subjects. Similarly, symptomatic subjects with LLN-COPD (n = 104) had DeltaFEV(1)% (2.0%; 95% CI, 0.8-3.3) and the hospitalization rate (RR, 4.18; 95% CI, 2.43-7.21) higher than the reference group. By contrast, nonsmokers and asymptomatic subjects with LLN-COPD had outcomes that were similar or even better than normal subjects. Among subjects with LLN-COPD, the association of symptoms with DeltaFEV(1)% varied according to smoking habits (P = 0.007); it was particularly strong in symptomatic smokers and disappeared in symptomatic nonsmokers. Similar results were found with the modified GOLD classification.In relatively young populations, COPD is associated with poor long-term outcomes in smokers and in symptomatic subjects only.
Streptococcus pneumoniae exposure is associated with human metapneumovirus seroconversion and increased susceptibility to in vitro HMPV infection
Authors: N.J. Verkaik, D.T. Nguyen, C.P. de Vogel, H.A. Moll, H.A. Verbrugh, V.W.V. Jaddoe, A. Hofman, W.J.B. van Wamel, B.G. van den Hoogen, R.M.G.B. Buijs-Offerman, M. Ludlow, L. de Witte, A.D.M.E. Osterhaus, A. van Belkum, R.L. de Swart
Journal: Clinical Microbiology and Infection (2011)
A global profiling of uncapped mRNAs under cold stress reveals specific decay patterns and endonucleolytic cleavages in Brachypodium distachyon
Authors: Jingyu Zhang, Zhiwei Mao, Kang Chong
Journal: Genome biology (2013)

Abstract Background mRNA degradation is a critical factor in determining mRNA abundance and enables rapid adjustment of gene expression in response to environmental stress. The involvement of processing bodies in stress response suggests a role for decapping-mediated mRNA degradation. However, little is known about the role of mRNA degradation under stressful environmental conditions. Results Here, we perform a global study of uncapped mRNAs, via parallel analysis of RNA ends (PARE), under cold stress in Brachypodium distachyon . Enrichment analysis indicates that degradation products detected by PARE are mainly generated by the decapping pathway. Endonucleolytic cleavages are detected, uncovering another way of modulating gene expression. PARE and RNA-Seq analyses identify four types of mRNA decay patterns. Type II genes, for which light-harvesting processes are over-represented in gene ontology analyses, show unchanged transcript abundance and altered uncapped transcript abundance. Uncapping-mediated transcript stability of light harvesting-related genes changes significantly in response to cold stress, which may allow rapid adjustments in photosynthetic activity in response to cold stress. Transcript abundance and uncapped transcript abundance for type III genes changes in opposite directions in response to cold stress, indicating that uncapping-mediated mRNA degradation plays a role in regulating gene expression. Conclusion To our knowledge, this is the first global analysis of mRNA degradation under environmental stress conditions in Brachypodium distachyon . We uncover specific degradation and endonucleolytic cleavage patterns under cold stress, which will deepen our understanding of mRNA degradation under stressful environmental conditions, as well as the cold stress response mechanism in monocots.
POST-INFLUENZAL RECOVERY FROM DEPRESSION
Authors: Max Levin
Journal: American Journal of Psychiatry (1933)

The patient had a nine-month depression at 28, precipitated by emotional shock and parturition. The depression cleared up completely coincidently with her recovery from a mild attack of influenza. She remained well until 40, when she entered her second depression, which at the present writing (2½ years after the onset) has not yet begun to lift.
The role of membrane receptors for C3b and C3d in phagocytosis.
Authors: A G Ehlenberger, V Nussenzweig
Journal: The Journal of Experimental Medicine (1977)

In this paper we re-examine the roles of particle-bound IgG and C3 in phagocytosis of sheep erythrocytes (E) by monolayers of purified human monocytes and polymorphonuclear leukocytes (PMN). We conclude that two fragments of the C3 molecule, that is, C3b and C3d, can function as opsonins if the phagocyte has the appropriate membrane receptors. Monocytes, that bind both C3b and C3d, respond to both as opsonins. PMN, which do not bind C3d, respond only to particles opsonized with C3b. C3 and IgG have separate roles in phagocytosis. IgG, through its Fc fragment, directly stimulates particle ingestion, but is relatively inefficient at inducing particle binding. On the other hand, C3 primarily mediates the binding of the particle via complement receptors. A marked synergy exists between C3 and IgG in inducing phagocytosis. Thus, opsonization of the particle with C3 can be a necessary condition for particle ingestion, although by itself C3 does not trigger phagocytosis. The opsonic effect of C3 can be mimicked by a variety of nonimmunologic agents which enhance binding of the particle to the phagocyte without directly stimulating ingestion. The contact-inducing agents used include centrifugation of particle and phagocyte, high molecular weight dextran, protamine, and treatment of E with neuraminidase. These results suggest that the role of C3 in opsonization is mainly or exclusively one of establishing contact between particle and phagocyte.
Cerebral venous thrombosis is associated with major vessel disease in Behcet's syndrome
Authors: R Tunc
Journal: Annals of the Rheumatic Diseases (2004)

To examine the association between the type of central nervous system (CNS) involvement (parenchymal disease and cerebral venous thrombosis (CVT)) and extra-cranial large vessel events, mainly venous thrombosis, in Behcet's syndrome (BS).Conventional venous angiograms, Doppler ultrasonography, computed tomography, and MR angiography were used to study 88 patients with BS, with (n = 88) and without (n = 80) CNS disease for the presence of major vessel disease.Major vessel involvement among the male patients with and without CNS disease (21/73 (29%) v 18/80 (23%), respectively) showed no significant differences (p = 0.374). When patients with CNS disease were stratified according to the type of CNS involvement, 7/11 (64%) patients with CVT had major vessel disease compared with 15/77 (19%) patients with parenchymal disease (p = 0.004). The mean (SD) age of onset of CVT (23.1 (8.8) years) among the male patients was significantly earlier than among the men with parenchymal disease (32.0 (7.5); p = 0.002).CVT in BS was strongly associated with peripheral major vessel disease and occurred earlier in the disease course than the parenchymal type of CNS disease. As superficial thrombophlebitis also occurs more frequently in patients with major vessel disease in BS, this may suggest a common pathogenic mechanism.
Multicenter phase III randomized trial of polychemotherapy (CVD regimen) versus the same chemotherapy (CT) plus subcutaneous interleukin-2 and interferon-α2b in metastatic melanoma
Authors: E. Bajetta, M. Del Vecchio, P. Nova, A. Fusi, A. Daponte, M.R. Sertoli, P. Queirolo, P. Taveggia, M.G. Bernengo, S.S. Legha, B. Formisano, N. Cascinelli
Journal: Annals of Oncology (2006)