tbuckley/cabot-search huggingface dataset:
Perception of lung function, adherence to inhaled corticosteroids, and the role of peak expiratory flow feedback in paediatric asthma
Authors: James Y Paton
Journal: Thorax (2012)

The current BTS/SIGN asthma guideline emphasises that the diagnosis of asthma is a clinical one with no standardised definition of the type, severity or frequency of symptoms, nor of the findings on investigation that invariably leads to a diagnosis of asthma.1 However, central to all definitions of asthma is the presence of variable airflow obstruction. Documenting a history of changes in airflow obstruction either after bronchodilator treatment (reversibility) or spontaneously (variability) is an essential part of an asthma diagnosis, as well as contributing to assessment of asthma control.

The variability of asthma in an individual has led to management strategies that educate and empower patients, or parents, to adjust their own therapy within a framework agreed with their clinician. This approach of ‘guided self- management’ has been shown to be effective in adults and children.2 ,3

Clark and Gong note that using a self-management approach acknowledges that clinicians cannot provide direction for every disease contingency. For effective disease control, patients need to exercise a high degree of independent decision making about adjusting their treatment. To do so, patients need to develop their own skills in self-management. Self-management is underpinned by the behavioural theory of self-regulation that has at its heart a cycle of ‘observation—judgment—reaction/s’.4 It is by repeated iterations of this cycle that patients develop their personal repertoire of asthma management strategies.

Two important questions necessarily arise. First, what observations best allow the patient/parent to monitor their asthma? Studies of self-management training programmes have commonly based asthma plans on assessment of symptoms and/or peak flow monitoring.2 ,3 ,5 ,6

Then, second, how best do clinicians ensure that patients are appropriately guided towards effective disease control? One problem is that, over time, a large number of patients fail to take prescribed medications in …
Clinical and physiological associations of some physical signs observed in patients with chronic airways obstruction
Authors: S. Godfrey, R. H. T. Edwards, E. J. M. Campbell, J. Newton-Howes
Journal: Thorax (1970)

A study of the relation between physical signs and the clinical and physiological pattern of chronic lung disease with obstruction has been carried out on 24 patients with varying degrees of airways obstruction. One sign (the forced expiratory time) was a direct reflection of the obstruction, but a number of other signs which also correlated significantly with the specific airway conductance were probably related to secondary effects on lung volume (increased resonance), disordered pattern of muscle action (tracheal tug and use of accessory muscles) or to excessive swings of intrathoracic pressure (excavation of supraclavicular fossae). Other signs which are regularly present but which did not correlate significantly with the severity of the airways obstruction were often related to other factors such as age or duration of symptoms (tracheal length). The difficulties in deciding the origin of other signs such as wheezes (rhonchi) or costal paradox are discussed.
FAK mediates the activation of cardiac fibroblasts induced by mechanical stress through regulation of the mTOR complex
Authors: Ana Paula Dalla Costa, Carolina F.M.Z. Clemente, Hernandes F. Carvalho, José B. Carvalheira, Wilson Nadruz, Kleber G. Franchini
Journal: Cardiovascular Research (2009)

Cardiac fibroblasts are activated by mechanical stress, but the underlying mechanisms involved remain poorly understood. In this study, we investigated whether focal adhesion kinase (FAK) plays a role in the activation of cardiac fibroblasts in response to cyclic stretch. Neonatal (NF-P3/80—third passage, 80% confluence) and adult (AF-P1/80—first passage, 80% confluence) rat cardiac fibroblasts were exposed to cyclic stretch (biaxial, 1 Hz), which enhanced FAK phosphorylation at Tyr397. Proliferation (anti-5-bromo-2′-deoxyuridine and anti-Ki67 nuclear labelling), differentiation into myofibroblasts (expression of alpha-smooth muscle actin—α-SMA), and the activity of matrix metalloproteinase-2 were equally enhanced in stretched NF-P3/80 and AF-P1/80. Treatment with the integrin inhibitor RGD peptide impaired FAK phosphorylation and increased apoptosis (TUNEL) in non-stretched and stretched NF-P3/80, whereas FAK silencing induced by small interfering RNA modestly enhanced apoptosis only in stretched cells. RGD peptide or FAK silencing suppressed the activation of NF-P3/80 invoked by cyclic stretch. In addition, NF-P3/80 depleted of FAK were defective in AKT Ser473, TSC-2 Thr1462, and S6 kinase Thr389 phosphorylation induced by cyclic stretch. The activation of NF-P3/80 invoked by cyclic stretch was prevented by pre-treatment with the mammalian target of rapamycin (mTOR) inhibitor rapamycin, whereas supplementation with the amino acid, leucine, activated S6K and rescued the stretch-induced activation of NF-P3/80 depleted of FAK. These findings demonstrate a critical role for the mTOR complex, downstream from FAK, in mediating the activation of cardiac fibroblasts in response to mechanical stress.
A step closer to cardiac optogenetics in vivo
Authors: E. Entcheva
Journal: Cardiovascular Research (2015)

This editorial refers to ‘Systemic gene transfer enables optogenetic pacing of mouse hearts’ by C.C. Vogt et al. , pp. 338–343. 

Imagine having the means to fully control excitation in the heart—to be able to trigger waves at precise locations and with desired properties and to be able to precisely manipulate such waves, including to selectively overwrite them (that is, to terminate an arrhythmia without brute force); imagine being able to do all this in the intact heart, in vivo , by light; imagine being able to ‘see’ all this in real time, optically. The idea of ‘all-optical cardiac electrophysiology’1,2 may seem like science fiction, but recent advances in optogenetics3–6 make it more and more tangible.

New technologies for cell-specific fast optical sensing or optical actuation have profoundly impacted neuroscience over the last decade and have become instrumental in the mechanistic dissection of brain function, in vivo. 7 These techniques rely on genetically encoded proteins, i.e. require genetic modification in the cells and tissues of interest, and most often employ transgenic animals. The cardiovascular area is lagging behind, and such transgenic mice, expressing optogenetic sensors and/or actuators, are still not widely available. Notably, the new CHROMus resource,8 sponsored by the National Institutes of Health in the USA, promises to supply a variety of relevant transgenic mouse models for the cardiovascular system, enabling optogenetic manipulation and imaging. Furthermore, new gene editing techniques open the door to affordable commercial …
Cabozantinib Inhibits Abiraterone's Upregulation of IGFIR Phosphorylation and Enhances Its Anti–Prostate Cancer Activity
Authors: Xiaodong Wang, Ying Huang, Amanda Christie, Michaela Bowden, Gwo-Shu Mary Lee, Philip W. Kantoff, Christopher J. Sweeney
Journal: Clinical Cancer Research (2015)

Abiraterone improves the overall survival of men with metastatic castration-resistant prostate cancer. However, de novo or adaptive resistance to abiraterone limits its activity. Rational combinations of drugs with different mechanisms of action that overcome resistance mechanisms may improve the efficacy of therapy. To that end, we studied the molecular and phenotypic effects of the combination of cabozantinib plus abiraterone.Three prostate cancer cell lines were used to interrogate the in vitro molecular and antiproliferative effects of the single agents and combination of cabozantinib and abiraterone. The in vivo impact of the combination was assessed using the LAPC4-CR xenograft mouse model.In vitro proliferation studies demonstrated single-agent doses between 2 μmol/L and 10 μmol/L for abiraterone and cabozantinib inhibit prostate cancer cell proliferation in a dose-dependent manner, and the anticancer activity of abiraterone is enhanced when combined with cabozantinib. In vivo LAPC4-CR xenograft mouse studies also showed that cabozantinib can improve the antitumor activity of abiraterone. Cabozantinib, a multiple receptor tyrosine kinase inhibitor, enhances the ability of abiraterone to inhibit AR activity in a cell line-dependent manner. In addition, our cell line studies demonstrate abiraterone-stimulated insulin-like growth factor I receptor (IGFIR) phosphorylation with downstream activation of MEK1/2 and ERK1/2, and that this potential adaptive resistance mechanism was inhibited by cabozantinib.Cabozantinib can enhance the efficacy of abiraterone by blocking multiple compensatory survival mechanisms, including IGFIR activation, and supports the assessment of the combination in a clinical trial.
Monozygotic twins concordant for narcolepsy-cataplexy without any detectable abnormality in the hypocretin (orexin) pathway
Authors: Ramin Khatami, Stéphanie Maret, Esther Werth, Julia Rétey, Dagmar Schmid, Friedrich Maly, Mehdi Tafti, Claudio L Bassetti
Journal: The Lancet (2004)
Macrolides for yet another chronic airway disease: severe asthma?
Authors: Peter G Gibson
Journal: Thorax (2013)

Macrolides have a macrocyclic lactone ring, whose size and features have been modified from the 14 carbon structure of erythromycin in order to develop newer agents such as azithromycin (AZM). They were originally derived from products the microbial order Actinomycetales (Saccharopolyspora erythrae , formerly Streptomyces erythrae ), and are yet another respiratory harvest from the organism that have given us many antibiotics, starting with the important antituberculosis drug, streptomycin. Macrolides are widely used as antibiotics, and now form part of guideline-recommended therapy in community-acquired pneumonia. They have an expanding role in the therapy of chronic inflammatory diseases based on their additional anti-inflammatory and immunosuppressive properties. Further development has produced broad-spectrum antibacterials, such as AZM, with a longer half-life, and minimal inhibition of cytochrome CYP3A4 and, hence, fewer drug interactions. Other developments in this class include tacrolimus and its derivatives that target macrophyllin-12 (FK506 binding protein) and are potent immunosuppressive agents.

The classical airway disease that responds to long-term low-dose macrolide therapy is diffuse panbronchiolitis in Asian populations.1 The pathological lesion is centred around the bronchioles and involves intense chronic inflammation, typically neutrophilic, leading to mucus hypersecretion, progressive loss of lung function, bacterial airway infection, and often death. Building on this paradigm, macrolides have been found to be effective in other airway …
Delayed-onset bronchiolitis obliterans with organising pneumonia associated with massive acetic acid steam inhalation
Authors: B-F Sheu, C-C Lee, Y-R Young, L-F Li, S-S Chang
Journal: Thorax (2008)

A 34-year-old worker had massive exposure to acetic acid steam from an explosion in a chemical factory. At the emergency department respiratory distress, hoarseness and swelling of the oropharyngeal mucosa were noted. The chest radiograph showed bilateral infiltration (fig 1). After being diagnosed with inhalation injury and chemical pneumonitis, he was prophylactically intubated and given parenteral steroid with prophylactic antibiotics. Diagnostic fibreoptic bronchoscopy revealed diffuse trachobronchial mucosal redness …
Point-of-care and point-of-procedure optical imaging technologies for primary care and global health
Authors: Stephen A. Boppart, Rebecca Richards-Kortum
Journal: Science Translational Medicine (2014)

Leveraging advances in consumer electronics and wireless telecommunications, low-cost, portable optical imaging devices have the potential to improve screening and detection of disease at the point of care in primary health care settings in both low- and high-resource countries. Similarly, real-time optical imaging technologies can improve diagnosis and treatment at the point of procedure by circumventing the need for biopsy and analysis by expert pathologists, who are scarce in developing countries. Although many optical imaging technologies have been translated from bench to bedside, industry support is needed to commercialize and broadly disseminate these from the patient level to the population level to transform the standard of care. This review provides an overview of promising optical imaging technologies, the infrastructure needed to integrate them into widespread clinical use, and the challenges that must be addressed to harness the potential of these technologies to improve health care systems around the world.
(5) Melkersson-Rosenthal syndrome
Authors: J.J. Cream, D. Wilson
Journal: British Journal of Dermatology (1983)

Journal Article (5) Melkersson‐Rosenthal syndrome Get access J. J. Cream, J. J. Cream Charing Cross Hospital, London Search for other works by this author on: Oxford Academic Google Scholar D. Wilson D. Wilson Charing Cross Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 109, Issue s24, 1 July 1983, Page 55, https://doi.org/10.1111/j.1365-2133.1983.tb11613.x Published: 01 July 1983
A FOLLOW-UP STUDY OF NON-LUETIC PSYCHOTIC PATIENTS WITH ABNORMALITIES IN THE SPINAL FLUID
Authors: PHILIP SOLOMON, ROBERT S. SCHWAB, LEO MALETZ
Journal: American Journal of Psychiatry (1940)

A follow-up study was made at the Boston Psychopathic Hospital of 165 non-luetic psychotic patients in whom the spinal fluid contained abnormalities. The patients were followed for an average period of three years. (1) In six, or 4 per cent, the abnormal findings were traced to errors in technique (laboratory error, or "bloody tap"). (2) In 70, or 42 per cent, confirmation was obtained for neurologic or metabolic conditions which were suspected at the time of the lumbar puncture as being responsible for the spinal fluid abnormalities. These conditions were: cerebral vascular disease, alcoholism, drug intoxication, encephalitis, brain trauma, brain tumor, multiple sclerosis, pellagra, and Huntington's chorea. (3) In 19, or 12 per cent, organic diseases were discovered in the follow-up study though at the time of the first spinal fluid examination, these diseases were not recognized. They were: cerebral vascular disease, brain tumor, alcoholism, myxedema, encephalitis, multiple sclerosis, intracranial tuberculoma, and Pott's disease of the spine. (4) In 70, or 42 per cent, the abnormal spinal fluid findings still remained unexplained. Thirty-five of these patients were schizophrenic, 17 manic-depressive.
Indirubin Derivative 6BIO Suppresses Metastasis
Authors: Simone Braig, Christine A. Kressirer, Johanna Liebl, Fabian Bischoff, Stefan Zahler, Laurent Meijer, Angelika M. Vollmar
Journal: Cancer Research (2013)

Abstract While metastasis is the chief cause of cancer mortality, there nonetheless remains a lack of antimetastatic therapies that are clinically available. In this study, we present the indirubin derivative 6-bromo-indirubin-3′-oxime (6BIO) as a promising antimetastatic agent. 6BIO strongly reduced formation of lung metastasis in the well-established 4T1 mouse model of aggressive breast cancer. Several major hallmarks of the metastatic process were affected by subtoxic concentrations of 6BIO, which inhibited adhesion, migration, and invasion of a variety of metastatic cell types in vitro. Mechanistic analyses focused on known targets of 6BIO, which were silenced by this compound. Unexpectedly, RNAi-mediated silencing of glycogen synthase kinase 3β (GSK3β) and phosphoinositide-dependent protein kinase 1 (PDK1), both modulators of cellular metastasis targeted by 6BIO, were not found to affect invasive migration in this study. Instead, the Jak/STAT3 signaling pathway appeared to play a major role through modulation of its downstream migration regulators C-terminal tensin-like protein and matrix metalloproteinase 2. However, PDK1 and GSK3β contributed to the overall response to 6BIO, as silencing of all three pathways resulted in almost complete inhibition of migration, phenocopying the 6BIO response. Taken together, our findings illustrate the antimetastatic activity of 6BIO on the basis of its ability to simultaneously inhibit several kinase cascades involved in metastasis of cancer cells, supporting the concept of “polypharmacology” in developing drugs to attack metastasis, the most deadly aspect of cancer. Cancer Res; 73(19); 6004–12. ©2013 AACR.
Elevated Depression Symptoms, Antidepressant Medicine Use, and Risk of Developing Diabetes During the Diabetes Prevention Program
Authors: Richard R. Rubin, Yong Ma, David G. Marrero, Mark Peyrot, Elizabeth L. Barrett-Connor, Steven E. Kahn, Steven M. Haffner, David W. Price, William C. Knowler
Journal: Diabetes Care (2008)

To assess the association between elevated depression symptoms or antidepressant medicine use on entry to the Diabetes Prevention Program (DPP) and during the study and the risk of developing diabetes during the study.
Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region
Authors: Marjolein J Peters, Linda Broer, Hanneke L D M Willemen, Gudny Eiriksdottir, Lynne J Hocking, Kate L Holliday, Michael A Horan, Ingrid Meulenbelt, Tuhina Neogi, Maria Popham, Carsten O Schmidt, Anushka Soni, Ana M Valdes, Najaf Amin, Elaine M Dennison, Niels Eijkelkamp, Tamara B Harris, Deborah J Hart, Albert Hofman, Frank J P M Huygen, Karen A Jameson, Gareth T Jones, Lenore J Launer, Hanneke J M Kerkhof, Marjolein de Kruijf, John McBeth, Margreet Kloppenburg, William E Ollier, Ben Oostra, Antony Payton, Fernando Rivadeneira, Blair H Smith, Albert V Smith, Lisette Stolk, Alexander Teumer, Wendy Thomson, André G Uitterlinden, Ke Wang, Sophie H van Wingerden, Nigel K Arden, Cyrus Cooper, David Felson, Vilmundur Gudnason, Gary J Macfarlane, Neil Pendleton, P Eline Slagboom, Tim D Spector, Henry Völzke, Annemieke Kavelaars, Cornelia M van Duijn, Frances M K Williams, Joyce B J van Meurs
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> Chronic widespread pain (CWP) is a common disorder affecting ∼10% of the general population and has an estimated heritability of 48–52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP. <h3>Methods</h3> We conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain. <h3>Results</h3> The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10<sup>−8</sup>). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7×10<sup>−7</sup>) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4×10<sup>−8</sup>, I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (p&gt;7.7×10<sup>−4</sup>). <h3>Conclusions</h3> We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.
The Effects of Electroconvulsive Therapy on Serial Electrocardiograms and Serum Cardiac Enzyme Values
Authors: G. William Dec
Journal: JAMA (1985)

Electroconvulsive therapy (ECT) is an effective, safe, and controversial treatment of severe depression. In order to further evaluate its safety, the effect of ECT on serial electrocardiograms and serum cardiac enzyme values was studied prospectively in 29 patients. Neither persistent electrocardiographic changes nor elevations in creatine phosphokinase or serum glutamic oxalaminase transaminase levels were observed following 85 treatments. Twenty-four percent of our patients had stable, preexisting cardiovascular disease, which included conduction system disease, recent myocardial infarction, and depressed ventricular function. Electroconvulsive therapy was well tolerated by all of these patients. The proposed mechanisms for transient or persistent electrocardiographic changes and cardiovascular complications of ECT are reviewed.
Fasting Plasma Free Fatty Acids and Risk of Type 2 Diabetes
Authors: James S. Pankow, Bruce B. Duncan, Maria Inês Schmidt, Christie M. Ballantyne, David J. Couper, Ron C. Hoogeveen, Sherita H. Golden
Journal: Diabetes Care (2004)

OBJECTIVE—To evaluate whether plasma levels of free fatty acids (FFAs) are independently associated with incidence of type 2 diabetes. RESEARCH DESIGN AND METHODS—A case-cohort design was used to randomly select 580 incident cases of diabetes and 566 noncases from 10,275 African-American and white men and women in the Atherosclerosis Risk in Communities study, aged 45–64 years and without prevalent diabetes at the baseline exam. Incident diabetes was ascertained at three exams over 9 years of follow-up. FFA levels were measured in plasma samples collected at the baseline exam. RESULTS—At baseline, FFA level was inversely associated with height and positively associated with female sex, BMI, waist circumference, waist-to-hip ratio, heart rate, plasma triglycerides, and an inflammation score quantifying levels of six systemic inflammation markers. Relative risks for incident diabetes (fourth vs. first quartile of FFAs) were increased in a basic model adjusted for age, sex, race, and center (hazard ratio 1.68, 95% CI 1.20–2.34) and in a model further adjusted for baseline fasting glucose, insulin, BMI, waist circumference, triglycerides, and the inflammation score (1.63, 1.04–2.57). Relative risks associated with a greater FFA level were lowest among those of normal weight and highest among the obese, but a formal test of interaction between FFAs and BMI was not statistically significant. CONCLUSIONS—Individuals with higher fasting levels of plasma FFAs were at modestly higher risk of type 2 diabetes in this cohort of middle-aged adults.