tbuckley/cabot-search huggingface dataset:
Mid-thigh intramuscular fat is associated with physical inactivity and quadriceps fibre type profile in patients with COPD
Authors: Matthew Maddocks, Dinesh Shrikrishna, Samantha Natanek, Simone Vitoriano, Rebecca Tanner, Nicholas Hart, Paul Kemp, John Moxham, Michael Polkey, Nicholas Hopkinson
Journal: European Respiratory Journal (2013)

Introduction:  Quadriceps muscle dysfunction is an important complication of COPD occurring in mild and more advanced disease. It is largely driven by physical inactivity and is characterised by atrophy and a shift towards a less aerobic phenotype, with reduced Type I fibre proportions and oxidative enzymes. We hypothesised that physical inactivity and fibre type shift would be associated with intramuscular fat and that this could be a non-invasive and non-volitional marker of muscle quality.   Methods : Mid-thigh cross-sectional area (MT CSA ) and percentage intramuscular fat were assessed using computed tomography (CT) image analysis. Tissues were differentiated using standard attenuation ranges; fat -190 to -30 and skeletal muscle -29 to 150 Hounsfield Units. Daily step count and physical activity level (PAL) were recorded using an armband accelerometer (SenseWear, Bodymedia). Type I and II fibre proportions were determined from vastus lateralis samples using immunohistochemistry. Associations were determined using multivariate regression models incorporating MT CSA  and age .    Results:  CT data were available for 102 patients (61 male, mean (SD) age 65(8) years, FEV 1  41(20)% predicted) and 10 age-matched healthy controls. Accelerometer and biopsy data were obtained in 69 and 58 participants respectively. Percentage intramuscular fat was higher in the patient group (6.7(3.5) vs 4.3(1.2)%, p   Conclusion:  Intramuscular fat assessed using CT reflects multiple aspects of muscle dysfunction in patients with COPD and may provide a valuable biomarker in this group.
Exostosis of the Vertebral Border of the Scapula: Removal
Authors: H. B. Robinson
Journal: BMJ (1899)

MXDICA JOUNL 963 venience.In thlree weeks after the operation she was sitting up, and in seven weeks, having taken fourteen days' holiday, she resumed her work.Nearly three years have passed since the operation, and I have every reason to believe she is still well.The operation lasted less than twenty minutes, and every circumstance favoured her recovery.The small size of the perforation, the absence of induration, the condition of surrounding peritoneum, the site of the ulcer, the small quantity and clharacter of the escaped contents, and the fact that only tlhree hours had elapsed since the rupture, all rendered the prognosis good and the operation easy.From a study of the airl's hiistory, and the appearance of the ulcer, the possibility of a tuberculous origin is worthy of note.The second case was sent to me at the Royal Southern Hospital on November 12th, I898, by Dr. Humphreys, who lad diagnosed a perforation: CASE II.History of A tacL.-The patient was a woman, aged 21. :Thirteenl hours previous to admission shc was seized with suddeni violent abdominal pain and vomitingr.I was in the hospital wlheil she was admitted at o'clock.She looked very distressed, complained of great tliirst, and sufered in-
XBP1: the last two decades
Authors: L H Glimcher
Journal: Annals of the Rheumatic Diseases (2009)

The transcription factor X box-binding protein 1 (XBP1) was isolated two decades ago in a search for regulators of major histocompatibility complex (MHC) class II gene expression. Many years of research finally revealed a protein with many functions, none of them related to the MHC. This paper provided an overview of what this multifunctional transcription factor actually does.
THE AFTER-RESULTS OF THE OPERATIVE TREATMENT OF HAEMORRHOIDS: A STUDY OF THREE HUNDRED CASES
Authors: H. G. Anderson
Journal: BMJ (1909)

RESULTS OF OPERATIONS FOR HAEMORRHOIDS.[OCT.3D, which some pain and smarting may be felt, and does not appreciably affect the action of the intestine later.For the bowels must not be "locked up."At first it was thought that, by preventing the passage of a stool for some days, rest and freedom from infection of the line of union
Historical and cultural variants on the good death
Authors: T. Walter
Journal: BMJ (2003)

Dominated by religion in the past and by medicine in the present: the idea of what constitutes a good death has changed in different cultures and societies throughout history, perhaps nowhere more so than in our globalised, Western cultures. After a period of individualisation, shared experiences with fellow sufferers now seem to be increasing in popularity 

Here is an account of the death of a French peasant in the 19th century:

> “She contracted a summer cholera. After four days she asked to see the village priest, who came and wanted to give her the last rites. 'Not yet, M. le cure; I'll let you know when the time comes.' Two days later: 'Go and tell M. le cure to bring me Extreme Unction.' “1 

This woman died a good death according to the lights of her society, but this is very different from the good death of modern Western societies. Firstly, she wanted to see the priest, not the doctor; today, dying is ruled not by religion but by medicine. Secondly, she died in a local community in which everyone knew their script; today, palliative care encourages individuals to write their own scripts for dying, as they do for living. Thirdly, the ars moriendi of her time assumed that she would die in a few days of an infectious disease; today, we are struggling to learn how to die much more slowly of the degenerative diseases of old age.

The good death depends on one's society and culture. Norms for the good death therefore vary widely within a multicultural society. In this article, I argue that cultural norms about the good death depend in particular on, firstly, the extent of secularisation, secondly, the extent of individualism, and thirdly, how long the typical death takes.

In tribal societies, to belong …
Tocolytic therapy for preterm delivery: systematic review and network meta-analysis
Authors: D. M. Haas, D. M. Caldwell, P. Kirkpatrick, J. J. McIntosh, N. J. Welton
Journal: BMJ (2012)

<b>Objective</b> To determine the most effective tocolytic agent at delaying delivery. <b>Design</b> Systematic review and network meta-analysis. <b>Data sources</b> Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012. <b>Study selection</b> Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery. <b>Data extraction</b> At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes). <b>Results</b> Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause). <b>Conclusions</b> Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes.
Sleep apnoea in heart failure
Authors: R. Schulz, A. Blau, J. Börgel, H. W. Duchna, I. Fietze, I. Koper, R. Prenzel, S. Schädlich, J. Schmitt, S. Tasci, S. Andreas
Journal: European Respiratory Journal (2007)

Studies from the USA have reported that sleep apnoea is common in congestive heart failure (CHF), with Cheyne-Stokes respiration (CSR) being the most frequent type of sleep-disordered breathing (SDB) in these patients. Within the present study, the authors sought to assess the prevalence and type of SDB among CHF patients in Germany. A total of 203 CHF patients participated in this prospective multicentre study. All patients were stable in New York Heart Association classes II and III and had a left ventricular ejection fraction (LVEF)<40%. The patients were investigated by polygraphy and all data were centrally analysed. Patient enrolment was irrespective of sleep-related symptoms. The majority of patients were male with a mean age of 65 yrs and hospitalised. Of the 203 patients, 145 (71%) had an apnoea/hypopnoea index>10.h(-1), obstructive sleep apnoea (OSA) occurred in 43% (n=88) and CSR in 28% (n=57) of patients. The prevalence of sleep-disordered breathing is high in patients with stable severe congestive heart failure from a European population. As sleep-disordered breathing may have a negative impact on the prognosis of congestive heart failure, a sleep study should be performed in every patient with congestive heart failure and a left ventricular ejection fraction of <40%. This diagnostic approach should probably be adopted for all of these patients irrespective of the presence of sleep-related symptoms.
Parallel RNA Interference Screens Identify EGFR Activation as an Escape Mechanism in <i>FGFR3</i>-Mutant Cancer
Authors: Maria Teresa Herrera-Abreu, Alex Pearson, James Campbell, Steve D. Shnyder, Margaret A. Knowles, Alan Ashworth, Nicholas C. Turner
Journal: Cancer Discovery (2013)

Abstract Activation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies. Significance: Our data identify a novel therapeutic approach to the treatment of FGFR3-mutant cancer, emphasizing the potential of combination approaches targeting both FGFR3 and EGFR. Our data extend the role of EGFR in mediating resistance to inhibitors targeting a mutant oncogene, showing that EGFR signaling can repress mutant FGFR3 to induce intrinsic resistance to FGFR targeting. Cancer Discov; 3(9); 1058–71. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 953
Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins.
Authors: Patrick Meraldi, Andrew D McAinsh, Esther Rheinbay, Peter K Sorger
Journal: Genome biology (2006)

Abstract Background Kinetochores are large multi-protein structures that assemble on centromeric DNA ( CEN DNA) and mediate the binding of chromosomes to microtubules. Comprising 125 base-pairs of CEN DNA and 70 or more protein components, Saccharomyces cerevisiae kinetochores are among the best understood. In contrast, most fungal, plant and animal cells assemble kinetochores on CEN s that are longer and more complex, raising the question of whether kinetochore architecture has been conserved through evolution, despite considerable divergence in CEN sequence. Results Using computational approaches, ranging from sequence similarity searches to hidden Markov model-based modeling, we show that organisms with CENs resembling those in S. cerevisiae (point CEN s) are very closely related and that all contain a set of 11 kinetochore proteins not found in organisms with complex CEN s. Conversely, organisms with complex CEN s (regional CEN s) contain proteins seemingly absent from point- CEN organisms. However, at least three quarters of known kinetochore proteins are present in all fungi regardless of CEN organization. At least six of these proteins have previously unidentified human orthologs. When fungi and metazoa are compared, almost all have kinetochores constructed around Spc105 and three conserved multi-protein linker complexes (MIND, COMA, and the NDC80 complex). Conclusion Our data suggest that critical structural features of kinetochores have been well conserved from yeast to man. Surprisingly, phylogenetic analysis reveals that human kinetochore proteins are as similar in sequence to their yeast counterparts as to presumptive Drosophila melanogaster or Caenorhabditis elegans orthologs. This finding is consistent with evidence that kinetochore proteins have evolved very rapidly relative to components of other complex cellular structures.
Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children
Authors: G.L. Piacentini, A. Bodini, S. Costella, Y. Suzuki, L. Zerman, C.G.B Peterson, A.L Boner
Journal: European Respiratory Journal (2000)

The purpose of the present study was to assess the possible relationships between exhaled nitric oxide (ENO), a circulating marker of eosinophil activation, serum eosinophil cationic protein (SECP), level of airway responsiveness to methacholine and lung function in asthmatic children, as well as to compare these markers between children with and without inhaled steroid therapy. In a cross-sectional study ENO, SECP and bronchial hyperresponsiveness to methacholine were evaluated in a group of 57 asthmatic children (21 without and 36 with regulator inhaled steroid therapy; aged 6-13 yrs). ENO was significantly lower in steroid treated children (p<0.01). No significant differences between steroid treated and untreated children were observed for the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1; PC20), SECP and FEV1. In the whole study population significant increase correlations were observed between PC20 and SECP (r=-0.329, p=0.013) and between ENO and FEV1% of predicted (r=-0.348, p<0.01). In the group not receiving inhaled steroids the inverse relationship between PC20 and SECP was more evident (r=-0.581, p<0.001). In the steroid-treated group a significant inverse relationship was observed between ENO and FEV1 (r=-0.426, p=0.0011). The level of exhaled nitric oxide and the relationships between lung function, bronchial reactivity and markers of inflammation are different between steroid-treated and untreated asthmatic children. This has implications for the monitoring of asthma in childhood.
Interferon Regulatory Factor 9 Protects Against Hepatic Insulin Resistance and Steatosis in Male Mice
Authors: Xin-An Wang, Ran Zhang, Dingsheng Jiang, Wei Deng, Shumin Zhang, Shan Deng, Jinfeng Zhong, Tao Wang, Li-Hua Zhu, Li Yang, Shufen Hong, Sen Guo, Ke Chen, Xiao-Fei Zhang, Zhigang She, Yingjie Chen, Qinglin Yang, Xiao-Dong Zhang, Hongliang Li
Journal: Hepatology (2013)

Obesity is a calorie-excessive state associated with high risk of diabetes, atherosclerosis, and certain types of tumors. Obesity may induce inflammation and insulin resistance (IR). We found that the expression of interferon (IFN) regulatory factor 9 (IRF9), a major transcription factor mediating IFN responses, was lower in livers of obese mice than in those of their lean counterparts. Furthermore, whole-body IRF9 knockout (KO) mice were more obese and had aggravated IR, hepatic steatosis, and inflammation after chronic high-fat diet feeding. In contrast, adenoviral-mediated hepatic IRF9 overexpression in both diet-induced and genetically (ob/ob) obese mice showed markedly improved hepatic insulin sensitivity and attenuated hepatic steatosis and inflammation. We further employed a yeast two-hybrid screening system to investigate the interactions between IRF9 and its cofactors. Importantly, we identified that IRF9 interacts with peroxisome proliferator-activated receptor alpha (PPAR-α), an important metabolism-associated nuclear receptor, to activate PPAR-α target genes. In addition, liver-specific PPAR-α overexpression rescued insulin sensitivity and ameliorated hepatic steatosis and inflammation in IRF9 KO mice.IRF9 attenuates hepatic IR, steatosis, and inflammation through interaction with PPAR-α.
S34 Lung Function in Children with Sickle Cell Disease: Abstract S34 Table 1
Authors: J Kirkby, R Bonner, P Bates, R Strunk, F Kirkham, J Stocks, S Sonnappa
Journal: Thorax (2012)

<h3>Introduction</h3> Sickle Cell Disease (SCD) is one of the most prevalent genetic diseases with an incidence of ∼1 in 200 Afro-Caribbean children in the UK (WHO; 2006). Since SCD can result in significant respiratory morbidity,<sup>[1]</sup> lung function tests (LFTs) could play an important role in the clinical management of children with SCD. <h3>Aim</h3> To determine the extent to which LFTs identify differences in children with SCD when compared with healthy Black children. <h3>Methods</h3> A respiratory health questionnaire was administered, and four commercially available LFTs (Impulse oscillometry (IOS), specific effective airways resistance (sReff), plethysmographic lung volumes, and spirometry) were undertaken in up to 214 healthy Black children and 85 children with SCD aged 4–12y. <h3>Results</h3> Amongst children with SCD, 50% reported cough on most days, and 25% had been reviewed by a specialist respiratory consultant within 3 months prior to the assessments. When compared with healthy children, 20% had a reduced total lung capacity (TLC), with concurrent reductions in FEV1 and FVC No differences in sReff were observed and IOS outcomes proved to be of limited value, due to poorly defined limits of normality and large between-subject variability. No significant group differences in bronchodilator responsiveness in SCD or healthy children were observed regardless of the outcome measured (Table 1). <h3>Conclusion</h3> Despite the high proportion of respiratory symptoms reported, the number of children with LFTs falling outside the limits of normal was relatively small. Results suggest a pattern of restrictive lung disease in children with SCD. Of the outcomes assessed, baseline spirometry appears to be the most useful for routine assessment of lung disease in young children with SCD. J Caboot, Curr Opin Pediatr 2008 Dencker, Clin Physiol Funct Imaging 2006 Kirkby, ERJ 2010 Kirkby, Ped Pulm 2012 Quanjer, ERJ 2012
Review: Daily aspirin reduces short-term risk for cancer and cancer mortality
Authors: Andrew K. Diehl
Journal: Annals of Internal Medicine (2012)

Source Citation Rothwell PM, Price JF, Fowkes FG, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379:1602-12. 22440946
A FOLLOW-UP STUDY OF MOTOR WITHDRAWAL REACTION TO HEAT DISCOMFORT IN PATIENTS BEFORE AND AFTER FRONTAL LOBOTOMY
Authors: WILLIAM P. CHAPMAN, AUGUSTUS S. ROSE, HARRY C. SOLOMON
Journal: American Journal of Psychiatry (1950)

1. A second-year follow-up study has been made of the intensity of heat stimulus causing motor withdrawal reaction in lobotomized patients. Measured amounts of heat were applied to the forehead by the Hardy-Wolff-Goodell pain threshold apparatus. The endpoints of motor withdrawal were the levels of heat causing the patient (1) to pull the head away from the apparatus and (2) to wince. Thirteen of the 23-patients originally tested were included in this study. 2. The results of the 13-24 months' follow-up test indicate that the decreased tolerance to heat discomfort noted in lobotomized patients during the first year after operation probably represented only a temporary change after lobotomy. 3. We have no adequate explanation either for the decreased tolerance to heat discomfort during the first postoperative year or for the tendency of the motor reaction pattern to return to the preoperative levels during the second postoperative year. A reasonable speculation could be that transection of the white matter in the frontal lobes removes a mechanism that inhibits withdrawal from discomfort. With the passage of time, some other mechanism in the central nervous system may take over such a role, which was previously the concern of the frontal lobes.
Impact of Body Mass Index on Outcomes and Treatment-Related Toxicity in Patients With Stage II and III Rectal Cancer: Findings From Intergroup Trial 0114
Authors: Jeffrey A. Meyerhardt, Joel E. Tepper, Donna Niedzwiecki, Donna R. Hollis, A. David McCollum, Denise Brady, Michael J. O'Connell, Robert J. Mayer, Bernard Cummings, Christopher Willett, John S. Macdonald, Al B. Benson, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2004)

To study the relationship between body mass index (BMI) and rates of sphincter-preserving operations, overall survival, cancer recurrence, and treatment-related toxicities in patients with rectal cancer.We evaluated a nested cohort of 1,688 patients with stage II and III rectal cancer participating in a randomized trial of postoperative fluorouracil-based chemotherapy and radiation therapy.Obese patients were more likely to undergo an abdominoperineal resection (APR) than normal-weight patients (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing adiposity in men was a strong predictor of having an APR (P <.0001). Obese men with rectal cancer were also more likely than normal-weight men to have a local recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity was not predictive of cancer recurrence in women, nor was BMI predictive of overall mortality in either men or women. Underweight patients had an increased risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight patients but no increase in cancer recurrences. Among all study participants, obese patients had a significantly lower rate of grade 3 to 4 leukopenia, neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity when compared with normal-weight individuals.Increasing BMI in male patients with rectal cancer is associated with a decreased likelihood of sphincter preservation and a higher chance of local recurrence. For both men and women, overweight and obese patients experience less toxicity associated with adjuvant chemoradiotherapy, suggesting that actual body weight dosing of fluorouracil for obese patients is justified.