tbuckley/cabot-search huggingface dataset:
Functions of lncRNA HOTAIR in lung cancer
Authors: Gregory Loewen, Janarthanan Jayawickramarajah, Ying Zhuo, Bin Shan
Journal: Journal of Hematology & Oncology (2014)

Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular processes. lncRNA HOX transcript antisense RNA (HOTAIR) represses gene expression through recruitment of chromatin modifiers. The expression of HOTAIR is elevated in lung cancer and correlates with metastasis and poor prognosis. Moreover, HOTAIR promotes proliferation, survival, invasion, metastasis, and drug resistance in lung cancer cells. Here we review the molecular mechanisms underlying HOTAIR-mediated aggressive phenotypes of lung cancer. We also discuss HOTAIR's potential in diagnosis and treatment of lung cancer, as well as the challenges of exploiting HOTAIR for intervention of lung cancer.
Incremental threshold loading: a standard protocol and establishment of a reference range in naive normal subjects
Authors: PH Johnson, AJ Cowley, WJ Kinnear
Journal: European Respiratory Journal (1997)

Incremental threshold loading (ITL) has been proposed as a test of inspiratory muscle strength and endurance. To date, however, there has been no standardized protocol for an ITL test, and no reference range, with different investigators using a variety of different pressure increments in small numbers of subjects. We developed an ITL test using the weighted plunger (WP) principle, which uses standard increments of pressure. In our protocol subjects inspire through the WP generating an initial threshold opening pressure of 10 cmH2O. This pressure is raised at 2 min intervals in increments of 5 cmH2O until they fail to lift the plunger on two consecutive attempted breaths. Sixty healthy volunteers (30 males and 30 females) aged 20-80 yrs performed the ITL test. Twelve subjects (six females and six males) performed the test twice to assess reproducibility and repeatability. Using stepwise multiple linear regression, we regressed the maximum threshold pressure sustained for a full 2 min (Pmax) against age, height, weight and static maximum inspiratory mouth pressure (MIP). Pmax was significantly related to age but not to either height or weight, the regression equation for males was Pmax (cmH2O)=103.8 - (1.0 x age in years), and for females was Pmax (cmH2O)=93.7 - (1.0 x age in years). The within-subject standard deviation for those repeating the ITL test was 5.4 cmH2O. Incremental threshold loading is a simple technique with good reproducibility, which most naive subjects can use without difficulty. By using standard pressure increments and performing the test in a large number of naive subjects, we have established a reference range that should be applicable wherever similar pressure increments are used.
Association of texture-based quantitative fibrotic patterns and pulmonary function test in a new validation set
Authors: Hyun Kim, Matthew Brown, Fereidoun Abtin, Peiyun Lu, Daniel Chong, Jonathan Goldin
Journal: European Respiratory Journal (2011)

Background:  Under non-volumetric CT scan, a texture-based quantitative lung fibrosis (QLF) score has been developed as a computer-aided diagnostic metric in a scleroderma-related interstitial lung disease (SSc-ILD) [1].   Objective:  To test an association the QLF from CT score with pulmonary function tests in new study cohort.   Methods:  From our anonymized research database, 119 subjects with SSc-ILD (mean age 48±10.6 years and 70.7% ±14.3 of FVC) underwent baseline CT scans with high-resolution, volumetric, 64 detectors in the prone position at full inspiration. The extents of fibrotic patterns were measured as a QLF score in 5 steps: 1) denoise images; 2) grid-sample at a fixed location; 3) convert the characteristics of intensities into texture features; 4) classify voxels as fibrotic or non-fibrotic patterns based on texture features and 5) report fibrotic voxels as percentages. Associations were tested by Spearman rank correlation.   Result:  Correlations between pulmonary function test and QLF were similar in the previous study and this new cohort as shown below.   Conclusion:  The quantitative fibrotic patterns in whole lung can be a useful prognostic metric of severity and the heterogeneity of distribution in fibrotic patterns in lobes can be used as an index.   Reference:   1Kim HJ, Tashkin DP, Clements PJ, et al. A computer-aided diagnosis system for quantitative scoring of extent of lung fibrosis in scleroderma patients. Clin Exp Rheumatol. 2010 (5 Suppl 62); S26-35.
Resistance of Acellular Dermal Matrix Materials to Microbial Penetration
Authors: Elizabeth N. Fahrenbach, Chao Qi, Omer Ibrahim, John Y. Kim, Murad Alam
Journal: JAMA Dermatology (2013)

Acellular dermal matrices have many current and potential applications, but their long-term safety has not been extensively studied. In particular, limited information exists regarding such materials' resistance to infection.To assess the resistance to microbial penetration of common acellular dermal matrix materials used in reconstruction after skin cancer excision, treatment of chronic ulcers and burns, breast reconstruction, hernia repairs, and other applications.Comparative in vitro study of 4 commercially available dermal substitutes for their ability to act as barriers to penetration by common skin pathogens.University-based dermatology and plastic surgery departments and a hospital microbiology laboratory.Four commercially available dermal substitutes, including AlloDerm (LifeCell), FlexHD (Musculoskeletal Transplant Foundation), Strattice (LifeCell), and NeoForm (Mentor Corporation).We tested the 4 dermal matrix materials with the following 4 organisms commonly implicated in wound infections: Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, and Candida albicans. Each material was inoculated with the same concentration of each pathogen.The number of bacterial colonies grown on blood agar plates.AlloDerm and rehydrated FlexHD were found to be the best barriers to penetration by P. aeruginosa. AlloDerm, FlexHD, and Strattice also prevented penetration by S. aureus and S. pyogenes; NeoForm was less effective in withstanding these organisms. The results of this study were inconclusive with regard to C. albicans penetration.Three of the 4 commonly used acellular dermal matrix materials are resistant to in vitro penetration by S. aureus and S. pyogenes and partially resistant to P. aeruginosa. Resistance to fungal pathogens is uncertain. Antimicrobial differences across matrix materials may influence their selection for particular uses, such as treatment of refractory leg ulcers or reconstruction after skin cancer excision.
A phase I dose escalation study of continuous oral capecitabine in combination with oxaliplatin and pelvic radiation (XELOX-RT) in patients with locally advanced rectal cancer
Authors: R. Glynne-Jones, D. Sebag-Montefiore, T.S. Maughan, S.J. Falk, A.C. McDonald
Journal: Annals of Oncology (2005)
OC-048 Colonoscopy: What is the Number Required to Maintain Competency? – a Retrospective Audit
Authors: C Kong, A N Young, K Benson, J J Keating, A H Davies
Journal: Gut (2013)

<h3>Introduction</h3> There has been increasing demand for gastroenterologist to maintain JAG competencies year on year.<sup>1</sup> However there are few studies into the adequate number required despite the bowel cancer screening programme suggesting &gt; 100 per annum. The study aims to compare competencies standards in relation to the number of colonoscopies performed in a year. <h3>Methods</h3> Data was collected retrospectively within the trust between 1/12/2010 and 30/11/2011. These include colonoscopies performed in the 3 main hospitals within the UHMBT – Royal Lancaster Infirmary, Furness General Hospital and Westmoreland General Hospital. A total of 2502 colonoscopies performed were retrieved. The endoscopy reporting system 'Endobase' and 'Indigo 4 Review' were used to retrieve endoscopy report and pathology report respectively. The caecal intubation rate (completion rate), polyp detection rate, adenoma detection rate, adequacy of bowel prep and sedation rate were set standards. Chi squared test for correlation was used to compare all standards. Two groups were formed to compare the set standards as colonoscopist who performed &gt; 100 colonoscopies per annum (pa) and those who performed &lt; 100 colonoscopies pa. Withdrawal time, polyp recovery and complication rates were not included in this audit. <h3>Results</h3> Of the 2502 colonoscopies performed, 633 were performed by colonoscopist who performed &lt; 100, 1869 colonoscopies were performed by colonoscopist who performed &gt; 100 colonoscopies. Completion rate for &lt; 100 colonscopies was 85.62% and &gt; 100 colonoscopies was 92.24% (p &lt; 0.0001). Polyp detection rate (PDR) for &lt;100 colonscopies was 17.85% and &gt; 100 colonoscopies was 30.34% (p &lt; 0.0001). Adenoma detection rate for &lt; 100 colonoscopies was 25.28% and &gt; 100 colonoscopies was 32.98% (p = 0.0003). Comparison of completion rates between both good and satisfactory bowel prep was 91.27% against poor prep 81.25% (p &lt; 0.001). Reasons for non completion in order of frequency were patient discomfort, excess looping, pathology encountered limiting progression, inadequate bowel preparation, tight stricture and instrument inadequacy. For sedation, the number of times pethidine given &gt; 50 mg was 0.15% and number of times midazolam given &gt; 5 mg was 0.05%. <h3>Conclusion</h3> Performing at least 100 colonoscopies a year statistically improves completion rate, polyp detection rate and adenoma detection rate. Good and satisfactory bowel prep statistically improves completion rate. This audit supports the JAG recommendation that a colonoscopist should perform &gt; 100 colonoscopies per annum to maintain competency. <h3>Disclosure of Interest</h3> None Declared <h3>Reference</h3> Valori R, Barton R. BSG quality and safety indicators for endoscopy. JAG: Joint Advisory Group on GI Endoscopy. 2007; 1–13.
Molecular evidence of organ-related transmission of Kaposi sarcoma–associated herpesvirus or human herpesvirus-8 in transplant patients
Authors: Mario Luppi, Patrizia Barozzi, Gaia Santagostino, Raffaella Trovato, Thomas F. Schulz, Roberto Marasca, Davide Bottalico, Lucia Bignardi, Giuseppe Torelli
Journal: Blood (2000)
Protective effects of preconditioning of the ischaemic myocardium involve cyclo-oxygenase products
Authors: A. Vegh, L. Szekeres, J. R Parratt
Journal: Cardiovascular Research (1990)

Study objective – The aim was to determine whether short (preconditioning) occlusions of a coronary artery protect against the arrhythmias occurring during a subsequent more prolonged occlusion and to examine whether the observed protection is mediated by the release of a product of the cyclo-oxygenase pathway of arachidonic acid metabolism. Design – The effects were examined of two short (5 min) coronary artery occlusions, in chloraloseurethane anaesthetised dogs, on a subsequent prolonged (25 min) occlusion; analysis of ischaemia and reperfusion induced arrhythmias and of epicardial ST segment changes was performed. Experimental material – 46 anaesthetised mongrel dogs in a restricted body weight range were used. Measurements and main results – Preconditioning reduced the incidence and severity of ischaemic arrhythmias during a 25 min occlusion. Ventricular premature beats (VPB) reduced from 445 (SEM 140) to 96(22) (p<0.0l), ventricular fibrillation (VF) from 4/10 to 0/20 (p<0.05), and ventricular tachycardia from 9/10 to 6/20 (p<0.05). VF following reperfusion was reduced from 6/6 to 6/10 (p<0.05). Preconditioning thus increased survival from the prolonged ischaemia-reperfusion insult from 0% to 40%. The protective effect of preconditioning was lost in the presence of the cyclo-oxygenase inhibitor sodium meclofenamate (2 mg·kg−1), eg, VPBs 367(95), VF during occlusion 1/9 and during reperfusion 8/8, survival 0%. Conclusions – Short, preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. That this protection is lost if the cyclo-oxygenase pathway is blocked suggests a protective role for prostanoids, most likely prostacyclin, as endogenous myocardial protective substances.
Utilization of Bone Marrow-Derived Endothelial Cell Precursors in Spontaneous Prostate Tumors Varies with Tumor Grade
Authors: Haiqing Li, William L. Gerald, Robert Benezra
Journal: Cancer Research (2004)

Abstract Id1 and Id3 genes are required for vascularization, growth, and metastasis of xenograft tumors. In Id-deficient mice, tumor transplantation and proangiogenic factors fail to mobilize and recruit circulating endothelial precursor cells (CEPs) and hematopoietic cells, leading to defective tumor angiogenesis in various models. To investigate the requirement of Id genes and bone marrow incorporation in spontaneous prostate tumors, we crossbred Id mutant mice with the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Id1−/− Id3+/− TRAMP mice display delayed tumor growth at 24 weeks compared with wild-type TRAMP mice. Id1 and Id3 were strongly expressed in the endothelial cells of poorly differentiated prostate adenocarcinoma but not in the vasculature of well-differentiated tumors, a finding that is corroborated in human prostate tumor samples. In Id-deficient TRAMP mice, the poorly differentiated tumors show extensive hemorrhage, whereas well-differentiated tumors exhibit none. Transplantation with Id wild-type bone marrow significantly reduced the hemorrhage in poorly differentiated prostate adenocarcinomas with bone marrow-derived endothelial cells contributing to 14% of the tumor blood vessels. However, in well-differentiated prostate adenocarcinomas, there was little evidence of bone marrow-derived endothelial cell incorporation. These differences in the expression of Id genes, the effects of Id loss, and the recruitment of bone marrow-derived endothelial precursor cells in tumor vasculature between well-differentiated and poorly differentiated prostate adenocarcinoma suggest that tumor angiogenesis varies depending on the tumor grade.
Prevailing Ethical Dilemmas in Terminal Care for Patients With Cancer in Taiwan
Authors: Tai-Yuan Chiu, Wen-Yu Hu, Hsien-Liang Huang, Chien-An Yao, Ching-Yu Chen
Journal: Journal of Clinical Oncology (2009)

The study aimed to investigate prevailing ethical dilemmas in terminal care for patients with cancer nationwide and identify related factors after the enactment of the Natural Death Act in Taiwan.This multicenter study surveyed 800 physicians and nursing staff of oncology wards and hospices through a set questionnaire. A total of 505 respondents (63.1%) who had taken care of patients with terminal cancer were analyzed.The most frequently encountered ethical dilemmas were truth-telling (mean +/- SD = 1.30 +/- 0.63; range [never, occasional, often], 0 to 2) and place of care (1.19 +/- 0.69), both of which were related to communication issues. Dilemmas related to clinical management were artificial nutrition and hydration (1.04 +/- 0.66) and use of antimicrobial agents (0.94 +/- 0.70). Logistic regression analyses revealed that positive attitudes about the Natural Death Act was negatively related to the extent of ethical dilemmas (odds ratio, 0.426; 95% CI, 0.256 to 0.710].The enactment of the Natural Death Act in Taiwan would contribute to improving the quality of end-of-life care, which suggests that this kind of law should be adopted in other countries. Educating cancer care professionals in building positive beliefs toward the act is strongly encouraged.
Clinical response to adalimumab: relationship to anti-adalimumab antibodies and serum adalimumab concentrations in rheumatoid arthritis
Authors: G. M Bartelds, C. A Wijbrandts, M. T Nurmohamed, S. Stapel, W. F Lems, L. Aarden, B. A C Dijkmans, P. P. Tak, G. J. Wolbink
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> A substantial proportion of patients with rheumatoid arthritis (RA) do not respond, or lose initial response, to adalimumab treatment. One explanation for non-response is that patients develop anti-adalimumab antibodies. <b>Objectives:</b> To evaluate the incidence of formation of antibody against adalimumab and the association with serum adalimumab concentrations and clinical response. <b>Methods:</b> In a cohort of 121 consecutive patients with RA treated with adalimumab, serum adalimumab concentrations and antibodies against adalimumab were measured together with clinical response variables before and up to 28 weeks after the start of treatment. <b>Results:</b> Anti-adalimumab antibodies were detected in 21 patients (17%) during 28 weeks of treatment. EULAR non-responders had antibodies significantly more often than good responders (34% vs 5%; p = 0.032). Patients with antibodies showed less improvement in disease activity (mean (SD) delta DAS28 0.65 (1.35)) than patients without antibodies (mean delta DAS28 1.70 (1.35)) (p = 0.001). Patients with antibodies during follow-up had lower serum adalimumab concentrations at 28 weeks than patients without antibodies (median 1.2 mg/l, range 0.0–5.6 vs median 11.0 mg/l, range 2.0–33.0, respectively; p&lt;0.001). Good responders had higher serum adalimumab concentrations than moderate responders (p = 0.021) and non-responders (p = 0.001). Concomitant methotrexate use was lower in the group with anti-adalimumab antibodies (52%) than in the group without antibodies (84%) (p = 0.003). <b>Conclusions:</b> Serum antibodies against adalimumab are associated with lower serum adalimumab concentrations and non-response to adalimumab treatment.
Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle
Authors: L. De Mattos-Arruda, B. Weigelt, J. Cortes, H.H. Won, C.K.Y. Ng, P. Nuciforo, F.-C. Bidard, C. Aura, C. Saura, V. Peg, S. Piscuoglio, M. Oliveira, Y. Smolders, P. Patel, L. Norton, J. Tabernero, M.F. Berger, J. Seoane, J.S. Reis-Filho
Journal: Annals of Oncology (2014)
Quantitative sacroiliac scintiscanning: a sensitive and objective method for assessing efficacy of nonsteroidal, anti-inflammatory drugs in patients with sacroiliitis.
Authors: N A Dunn, B H Mahida, M V Merrick, G Nuki
Journal: Annals of the Rheumatic Diseases (1984)

Serial computer assisted quantitative sacroiliac scintiscanning (SI joint/sacrum ratios) 3 hours after low dosage (5 mCi) 99mTc methylene diphosphonate has been used as an objective index of sacroiliitis in a single blind 14-day cross-over comparison of azapropazone 600 mg b.d. and naproxen 500 mg b.d. in 18 patients with active sacroiliitis. Clinical assessments included visual analogue scales for measurement of pain and early morning stiffness, chest expansion, a modified Schober test, and goniometric measurement of thoracolumbar spinal flexion by means of an inclinometer. Statistically significant decreases in pain (p less than 0.001) and early morning stiffness (p less than 0.001) followed treatment with each NSAID, but there was no significant difference in the fall in these parameters, although 15 out of 18 patients expressed a preference for naproxen. Chest expansion and thoracolumbar flexion were not significantly affected by either drug. Serial quantitative scintigraphy showed a mean fall in joint sacrum ratios following each treatment which was statistically significant (p less than 0.02) only after naproxen. Serial quantitative scintigraphy can be used as an objective method of assessing sacroiliitis and was sufficiently sensitive to reflect the patients9 subjective preference in a short-term comparison of 2 NSAID.
Gross and Microscopic Pathological Changes Associated With Nonthoracotomy Implantable Defibrillator Leads
Authors: Andrew E. Epstein, G. Neal Kay, Vance J. Plumb, Sharon M. Dailey, Peter G. Anderson
Journal: Circulation (1998)

Although the effects of epicardial implantable cardioverter-defibrillator (ICD) leads on underlying cardiac tissue have been reported, the gross and microscopic changes associated with endocardial ICD leads are less well described. This study describes the gross and microscopic changes associated with endocardial ICD leads in humans.The hearts from 8 patients were examined. At the time of ICD implantation, the patients' mean age was 47+/-11 years, and the left ventricular ejection fraction was 0.24+/-0.10. Four patients had ischemic heart disease, and 4 had dilated cardiomyopathy. Five hearts were examined after transplantation; 3, after death. The electrode-myocardial interfaces were characterized by intense endocardial fibrosis and were remarkably consistent. Each lead was encased by a ring of fibroelastic tissue, and there was fibrosis of the right ventricular myocardium adjacent to the leads. Fibrosis involved the tricuspid valve in 5 patients, and 1 had perforation of the valve by the lead. Microscopically, interstitial fibrosis was adjacent to each lead in the current path of ICD shocks. Acute cell injury was present only in the hearts that had received recent shocks.The ICD electrode-myocardial interface is characterized by intense fibrosis. The fibrosis associated with endocardial ICD leads and the cumulative acute damage produced by defibrillation discharges may explain changes in the defibrillation and pacing thresholds and the difficulty of lead extraction that can be encountered with transvenous ICD systems.
Interstitial lung disease: are we missing formes frustes of connective tissue disease?
Authors: Vincent Cottin
Journal: European Respiratory Journal (2006)

Patients with connective tissue disease (CTD) may encompass a variety of respiratory manifestations, including: pleural disease; pulmonary hypertension; bronchial or bronchiolar disease; interstitial pneumonia; restrictive lung disease secondary to musculo-skeletal changes; and iatrogenic drug-induced lung disease. Patients also have an increased risk of opportunistic infections, often favoured by corticosteroids and/or immunosuppressive or immunomodulatory therapy 1, 2. The respective frequency of manifestations, their clinical and radiological presentations, response to treatment, and outcome are dependent on the underlying CTD.

Rheumatoid arthritis may be responsible for a broad spectrum of manifestations, including: pleural effusion; chronic interstitial pneumonia; lung rheumatoid nodules; bronchiectasis; obstructive ventilatory defect due to constrictive bronchiolitis; laryngeal involvement; and opportunistic infections, such as mycobacterial infections facilitated by anti-tumour necrosis factor-α treatments. Systemic sclerosis may be commonly associated with chronic interstitial pneumonia (especially in patients with diffuse systemic sclerosis and anti-topoisomerase-1 antibodies), or pulmonary arterial hypertension (most frequently, but not exclusively, in patients with limited systemic sclerosis with anti-centromere antibodies), with both contributing to the unfavourable prognosis of the disease 3.

Although less frequent among CTDs than rheumatoid arthritis and systemic sclerosis, the spectrum of idiopathic inflammatory myopathy (including dermatomyositis, polymyositis, and amyopathic dermatomyositis) may give rise to a variety of respiratory manifestations, which represent a common cause of death in these patients. These include interstitial lung disease (ILD), aspiration pneumonia, ventilatory failure secondary to diaphragmatic dysfunction 4, and rarely, acute respiratory distress syndrome, pleural effusion, pneumothorax, pulmonary hypertension 5, diffuse alveolar haemorrhage, and dyspnoea due to dermatopolymyositis-related cardiac disease 2, 6. In addition, some manifestations may be the consequence of treatment, such as drug-induced pneumonitis and opportunistic infections. First described in 1986 7, the high frequency of pneumomediastinum in dermatomyositis has been better appreciated more recently 8.

The association of ILD and …