tbuckley/cabot-search huggingface dataset:
Transcriptional Reversion of Cardiac Myocyte Fate During Mammalian Cardiac Regeneration
Authors: Caitlin C. O’Meara, Joseph A. Wamstad, Rachel A. Gladstone, Gregory M. Fomovsky, Vincent L. Butty, Avanti Shrikumar, Joseph B. Gannon, Laurie A. Boyer, Richard T. Lee
Journal: Circulation Research (2014)

Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine whether myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte (CM) regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo CM differentiation, in vitro CM explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of CM differentiation processes, including reactivation of latent developmental programs similar to those observed during destabilization of a mature CM phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13, which induced CM cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of interleukin 13 signaling in CMs. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration.
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose
Authors: Scott P. Commins, Hayley R. James, Libby A. Kelly, Shawna L. Pochan, Lisa J. Workman, Matthew S. Perzanowski, Katherine M. Kocan, John V. Fahy, Lucy W. Nganga, Eva Ronmark, Philip J. Cooper, Thomas A.E. Platts-Mills
Journal: Journal of Allergy and Clinical Immunology (2011)
Quality improvement report: Effect of a scoring system and protocol for sedation on duration of patients' need for ventilator support in a surgical intensive care unit
Authors: G. Brattebo
Journal: BMJ (2002)

Need for improved sedation strategy for adults receiving ventilator support.Observational study of effect of introduction of guidelines to improve the doctors' and nurses' performance. The project was a prospective improvement and was part of a national quality improvement collaborative.A general mixed surgical intensive care unit in a university hospital; all doctors and nurses in the unit; all adult patients (>18 years) treated by intermittent positive pressure ventilation for more than 24 hours.Reduction in patients' mean time on a ventilator and length of stay in intensive care over a period of 11 months; anonymous reporting of critical incidents; staff perceptions of ease and of consequences of changes.Multiple measures (protocol development, educational presentations, written guidelines, posters, flyers, emails, personal discussions, and continuous feedback) were tested, rapidly assessed, and adopted if beneficial.Mean ventilator time decreased by 2.1 days (95% confidence interval 0.7 to 3.6 days) from 7.4 days before intervention to 5.3 days after. Mean stay decreased by 1.0 day (-0.9 to 2.9 days) from 9.3 days to 8.3 days. No accidental extubations or other incidents were identified.Relatively simple changes in sedation practice had significant effects on length of ventilator support. The change process was well received by the staff and increased their interest in identifying other areas for improvement.
Distribution and function of the peptide transporter PEPT2 in normal and cystic fibrosis human lung
Authors: D A Groneberg
Journal: Thorax (2002)

Background: Aerosol administration of peptide based drugs has an important role in the treatment of various pulmonary and systemic diseases. The characterisation of pulmonary peptide transport pathways can lead to new strategies in aerosol drug treatment. Methods: Immunohistochemistry and ex vivo uptake studies were established to assess the distribution and activity of the β-lactam transporting high affinity proton coupled peptide transporter PEPT2 in normal and cystic fibrosis human airway tissue. Results: PEPT2 immunoreactivity in normal human airways was localised to cells of the tracheal and bronchial epithelium and the endothelium of small vessels. In peripheral lung immunoreactivity was restricted to type II pneumocytes. In sections of cystic fibrosis lung a similar pattern of distribution was obtained with signals localised to endothelial cells, airway epithelium, and type II pneumocytes. Functional ex vivo uptake studies with fresh lung specimens led to an uptake of the fluorophore conjugated dipeptide derivative d-Ala-l-Lys-AMCA into bronchial epithelial cells and type II pneumocytes. This uptake was competitively inhibited by dipeptides and cephalosporins but not ACE inhibitors, indicating a substrate specificity as described for PEPT2. Conclusions: These findings provide evidence for the expression and function of the peptide transporter PEPT2 in the normal and cystic fibrosis human respiratory tract and suggest that PEPT2 is likely to play a role in the transport of pulmonary peptides and peptidomimetics.
Mechanisms of Altered Excitation-Contraction Coupling in Canine Tachycardia-Induced Heart Failure, II
Authors: Raimond L. Winslow, Jeremy Rice, Saleet Jafri, Eduardo Marbán, Brian O’Rourke
Journal: Circulation Research (1999)

Abstract —Ca 2+ transients measured in failing human ventricular myocytes exhibit reduced amplitude, slowed relaxation, and blunted frequency dependence. In the companion article (O’Rourke B, Kass DA, Tomaselli GF, Kääb S, Tunin R, Marbán E. Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart, I: experimental studies. Circ Res . 1999;84:562–570), O’Rourke et al show that Ca 2+ transients recorded in myocytes isolated from canine hearts subjected to the tachycardia pacing protocol exhibit similar responses. Analyses of protein levels in these failing hearts reveal that both SR Ca 2+ ATPase and phospholamban are decreased on average by 28% and that Na + /Ca 2+ exchanger (NCX) protein is increased on average by 104%. In this article, we present a model of the canine midmyocardial ventricular action potential and Ca 2+ transient. The model is used to estimate the degree of functional upregulation and downregulation of NCX and SR Ca 2+ ATPase in heart failure using data obtained from 2 different experimental protocols. Model estimates of average SR Ca 2+ ATPase functional downregulation obtained using these experimental protocols are 49% and 62%. Model estimates of average NCX functional upregulation range are 38% and 75%. Simulation of voltage-clamp Ca 2+ transients indicates that such changes are sufficient to account for the reduced amplitude, altered shape, and slowed relaxation of Ca 2+ transients in the failing canine heart. Model analyses also suggest that altered expression of Ca 2+ handling proteins plays a significant role in prolongation of action potential duration in failing canine myocytes.
Studies on the quantitation of immunoglobulin in human intestinal secretions
Authors: R. R. Samson, D. B. L. McClelland, D. J. C. Shearman
Journal: Gut (1973)

There is increasing evidence for the importance of the secretory immune system in the gut. In studies of local antibody production it is important to have satisfactory methods for measuring immunoglobulin concentrations and to be aware of the errors which may occur. Studies on immunoglobulin measurement in intestinal secretion by the radial immunodiffusion method are reported, showing the effects of proteolytic digestion, IgA molecular size, and sampling and storage conditions. Because of the presence of monomeric IgA in addition to secretory IgA, there is no satisfactory standard for IgA in gastrointestinal secretions, and only semi-quantitative results can be given. With radial immunodiffusion, IgG and IgM when subjected to tryptic digestion, and IgA when subjected to peptic digestion, may be overestimated because of the presence of fragments of immunoglobulins. In addition, pepsin rapidly destroys IgM and IgG. Both IgM and IgG are unstable in storage. The findings suggest that immunoglobulin concentration measurements in small intestinal aspirates should be interpreted with caution. These problems are also relevant to the detection of specific antibodies in gastrointestinal secretions.
Monitoring asthma in children
Authors: Mariëlle W. Pijnenburg, Eugenio Baraldi, Paul L.P. Brand, Kai-Håkon Carlsen, Ernst Eber, Thomas Frischer, Gunilla Hedlin, Neeta Kulkarni, Christiane Lex, Mika J. Mäkelä, Eva Mantzouranis, Alexander Moeller, Ian Pavord, Giorgio Piacentini, David Price, Bart L. Rottier, Sejal Saglani, Peter D. Sly, Stanley J. Szefler, Thomy Tonia, Steve Turner, Edwina Wooler, Karin C. Lødrup Carlsen
Journal: European Respiratory Journal (2015)

The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different individuals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence.
Improved lung function and symptom control with formoterol on demand in asthma
Authors: D. Cheung, H. C. J. van Klink, R. Aalbers
Journal: European Respiratory Journal (2006)

Many asthma patients remain symptomatic despite maintenance therapy with inhaled corticosteroids (ICS) and salbutamol as rescue medication. In the present study the relative efficacy and preference for as-needed formoterol compared with salbutamol was examined. In total, 211 patients with a mean age of 45 yrs (mean forced expiratory volume in one second (FEV 1 ) 77% predicted normal), using ICS, were randomised to 3 weeks' double-blind treatment with as-needed formoterol 4.5 μg Turbuhaler® and with as-needed salbutamol 100 μg Turbuhaler® in a cross-over fashion. Overall, lung function and symptom control were better with as-needed formoterol than with as-needed salbutamol. During as-needed formoterol treatment daytime and night-time symptom scores were lower, peak expiratory flow and FEV 1 were higher and patients experienced fewer disturbed nights (34%) compared with as-needed salbutamol. Patients preferred the formoterol treatment to salbutamol. Of the 162 patients expressing a preference, formoterol was preferred by 68% (95% confidence interval: 60–75). Subjective assessment of effectiveness also favoured formoterol, which was perceived as slightly faster acting than salbutamol. In conclusion, as-needed formoterol improved symptoms and lung function compared with salbutamol and was perceived as more effective and at least as fast acting for symptom relief.
Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer
Authors: Di Zhao, Shao-Wu Zou, Ying Liu, Xin Zhou, Yan Mo, Ping Wang, Yan-Hui Xu, Bo Dong, Yue Xiong, Qun-Ying Lei, Kun-Liang Guan
Journal: Cancer Cell (2013)
Human-to-human transmission of <i>Mycobacterium kansasii</i> or victims of a shared source?
Authors: William M. Ricketts, Terence C. O’Shaughnessy, Jakko van Ingen
Journal: European Respiratory Journal (2014)

To the Editor: 

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment [1] and can cause opportunistic infections in humans with either an immunological deficit or structurally abnormal lungs, such as in cystic fibrosis, bronchiectasis or chronic obstructive pulmonary disease (COPD) [2]. Unlike Mycobacterium tuberculosis , human-to-human transmission of NTM is generally thought to be uncommon [2–4], although there is evidence that transmission of certain NTM is possible in certain circumstances [5]. Domestic plumbing has also been suggested as a potential source of infection [6].

We describe what we believe to be the best evidence to date of human-to-human transmission of Mycobacterium kansasii in a husband and wife living in East London, UK, an area with a high incidence of tuberculosis (∼112 cases per 100 000 per year) [7]. A recent survey suggested a UK isolation rate for NTM of around three cases per 100 000 per year with no data available for true disease incidence [8].

The first of the couple to be seen in chest clinic was a 69-year-old Caucasian …
Null hypothesis tests and theory corroboration: Defending NHSTP out of context
Authors: Reuven Dar
Journal: Behavioral and Brain Sciences (1998)

Chow's defense of NHSTP ignores the fact that in psychology it is used to test substantive hypotheses in theory-corroborating research. In this role, NHSTP is not only inadequate, but damaging to the progress of psychology as a science. NHSTP does not fulfill the Popperian requirement that theories be tested severely. It also encourages nonspecific predictions and feeble theoretical formulations.
Government disputes that half of NHS efficiency savings came from staff pay freeze
Authors: A. O'Dowd
Journal: BMJ (2012)

The government does not accept the claim made by representatives of NHS trusts that half of the latest £5.8bn (€7.2bn; $9.2bn) efficiency savings made by the NHS in 2011-12 resulted from staff pay being frozen.

Health secretary Jeremy Hunt, making his first appearance before the parliamentary health select committee on 13 November as part of its inquiry into public expenditure, said that the government estimated that around a third (£1.5bn) of the efficiency savings was linked to pay issues last year.

MPs also pushed the health secretary to explain why around £1bn worth of efficiency savings made by the NHS was handed back to the Treasury last year rather than being directly …
Hours of Television Viewing and Sleep Duration in Children
Authors: Marcella Marinelli, Jordi Sunyer, Mar Alvarez-Pedrerol, Carmen Iñiguez, Maties Torrent, Jesús Vioque, Michelle C. Turner, Jordi Julvez
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> This study used longitudinal data to examine potential associations between hours of television viewing and sleep duration in children. <h3>Objective</h3> To examine the association between hours of television viewing and sleep duration in preschool and school-aged children. <h3>Design, Setting, and Participants</h3> Longitudinal, multicenter study among birth cohorts in Menorca, Sabadell, and Valencia from the Spanish Infancia y Medio Ambiente (environment and childhood) project. The study sample included 1713 children (468 from Menorca, 560 from Sabadell, and 685 from Valencia). <h3>Exposure</h3> Parent-reported child television viewing duration measured in hours per day at 2 and 4 years of age in Sabadell and Valencia and at 6 and 9 years of age in Menorca. <h3>Main Outcomes and Measures</h3> Parent-reported child sleep duration measured in hours per day at 2 and 4 years of age in Sabadell and Valencia and at 6 and 9 years of age in Menorca. <h3>Results</h3> In cross-sectional analysis, children with longer periods of television viewing reported at baseline (≥1.5 hours per day) had shorter sleep duration. Longitudinally, children with reported increases in television viewing duration over time (from &lt;1.5 to ≥1.5 hours per day) had a reduction in sleep duration at follow-up visits. Results were similar when examining television viewing duration as a continuous variable, with each 1 hour per day of increased viewing decreasing sleep duration at follow-up visits (β = −0.11; 95% CI, –0.18 to −0.05). Associations were similar when television viewing duration was assessed during weekends and after adjusting for potential intermediate factors (child executive function and attention-deficit/hyperactivity disorder symptoms) and confounders (child physical activity level, parental mental health status, maternal IQ, and maternal marital status). <h3>Conclusions and Relevance</h3> Children spending longer periods watching television had shorter sleep duration. Changes in television viewing duration were inversely associated with changes in sleep duration in longitudinal analysis. Parents should consider avoiding long periods of daily television exposure among preschool and school-aged children.
Stimulation of the B-cell receptor activates the JAK2/STAT3 signaling pathway in chronic lymphocytic leukemia cells
Authors: Uri Rozovski, Ji Yuan Wu, David M. Harris, Zhiming Liu, Ping Li, Inbal Hazan-Halevy, Alessandra Ferrajoli, Jan A. Burger, Susan O’Brien, Nitin Jain, Srdan Verstovsek, William G. Wierda, Michael J. Keating, Zeev Estrov
Journal: Blood (2014)
MALE HOMOSEXUALITY, PARANOIA, AND THE SCHIZOPHRENIAS
Authors: ROBERT A. MOORE, MELVIN L. SELZER
Journal: American Journal of Psychiatry (1963)

Two hundred and five male schizophrenic inpatients receiving intensive psychotherapy were studied to determine the relative estimate of homosexual orientation between 128 paranoid schizophrenics and a control group of 77 non-paranoid schizophrenics. Previous theoretical and research publications suggested a difference would be found, and this was found to be true. To a statistically significant degree, the paranoids showed greater incidence of past overt homosexual acts, preoccupation during therapy with homosexuality, and were judged latently homosexual more often by both psychiatrists and testing psychologists. Anticipation of homosexuality as a great threat to paranoids aids in planning their therapy to avoid unnecessary storms or frightened withdrawal. Since a considerable number of non-paranoid schizophrenics is also troubled by homosexual desires, latent or overt, other factors must be sought if we are to understand why paranoids are paranoid.
Flap Operating in Laminectomy and Subcutaneous Cysts
Authors: C. H. Golding-Bird
Journal: BMJ (1895)

BRITISH 11 fell from the top of a hayrick, and, although the fall wvas from a considerable height, she soon recovered from the shock, and there was no further injury apparent at the time.In the course of a few weeks, however, she had what appears to have been an epileptic seizare.She suddenly fell down and be- came unconscious, and the mother immediately noticed she could not move her right arm and leg.The face was not affect ed.InJqly, 1892, she had two slight epileptic seizures, andagain in July, 1893 (six months prior to her admission), she had several seizures, but these were not followed by any appre-
Type I Insulin-like Growth Factor Receptor as a Therapeutic Target in Cancer
Authors: Bradley S. Miller, Douglas Yee
Journal: Cancer Research (2005)

Abstract Data from experimental model systems and population studies have implicated type I insulin-like growth factor receptor (IGF1R) signaling in many different human cancers. Drugs to disrupt IGF1R function have been developed and are now entering clinical trial. This brief review will identify key areas to consider as these clinical trials move forward.
<i>BRAF</i> V600E Mutation Identifies a Subset of Low-Grade Diffusely Infiltrating Gliomas in Adults
Authors: Andrew S. Chi, Tracy T. Batchelor, Daniel Yang, Dora Dias-Santagata, Darrell R. Borger, Leif W. Ellisen, A. John Iafrate, David N. Louis
Journal: Journal of Clinical Oncology (2013)
Selective Decrease in Urinary Aquaporin 2 and Increase in Prostaglandin E2 Excretion Is Associated with Postobstructive Polyuria in Human Congenital Hydronephrosis
Authors: Luisa Murer, Francesco Addabbo, Monica Carmosino, Giuseppe Procino, Grazia Tamma, Giovanni Montini, Waifro Rigamonti, Pietro Zucchetta, Manuela Della Vella, Alessandra Venturini, Graziella Zacchello, Maria Svelto, Giovanna Valenti
Journal: Journal of the American Society of Nephrology (2004)

This study was undertaken to determine the role of aquaporin 2 (AQP2) in the impaired urinary concentrating capacity observed in patients who underwent pyeloplasty because of congenital unilateral hydronephrosis as a result of pyeloureteral junction disease. Twelve children (mean age, 8 ± 2 mo) were examined in the study. From day 1 to day 5 after surgery, the urine was collected separately from pyelostomy draining only from the postobstructed kidney and from the bladder catheter draining mostly from the contralateral kidney used as internal control. After pyeloplasty, the postobstructed kidney was characterized by a reduced urinary excretion of AQP2 (∼54%) associated with polyuria that persisted from day 1 to day 5 (433 ± 58 <i>versus</i> 310 ± 74 ml/24 h at day 1; 326 ± 44 <i>versus</i> 227 ± 26 ml/24 h at day 5). In parallel, urine osmolality from the postobstructed kidney was significantly reduced compared with the contralateral kidney (111 ± 12 <i>versus</i> 206 ± 49 at day 1; 136 ± 24 <i>versus</i> 235 ± 65 mOsm/kg at day 5). Creatinine clearance from the postobstructed kidney was not significantly different compared with the contralateral kidney throughout the 4 d after surgery. However, on day 5, creatinine clearance from the postobstructed kidney became significantly lower. Prostaglandin E2 in the urine from postobstructed kidneys was found to be twofold higher than in the contralateral samples (26.0 ± 6.7 <i>versus</i> 13.5 ± 2.5 at day 5). It is concluded that (<i>1</i>) the selective downregulation of AQP2 in postobstructed kidney may account for the higher excretion of hypotonic urine, and (2) the local increase in prostaglandin E2 synthesis in postobstructed kidney may be involved in AQP2 downregulation and in maintaining a GFR similar to that of the contralateral kidney.