tbuckley/cabot-search huggingface dataset:
Copy Number Aberrations of Genes Regulating Normal Thymus Development in Thymic Epithelial Tumors
Authors: Iacopo Petrini, Yisong Wang, Paolo A. Zucali, Hye Seung Lee, Trung Pham, Donna Voeller, Paul S. Meltzer, Giuseppe Giaccone
Journal: Clinical Cancer Research (2013)

Abstract Purposes: To determine whether the deregulation of genes relevant for normal thymus development can contribute to the biology of thymic epithelial tumors (TET). Experimental Design: Using array comparative genomic hybridization, we evaluated the copy number aberrations of genes regulating thymus development. The expression of genes most commonly involved in copy number aberrations was evaluated by immunohistochemistry and correlated with patients' outcome. Correlation between FOXC1 copy number loss and gene expression was determined in a confirmation cohort. Cell lines were used to test the role of FOXC1 in tumors. Results: Among 31 thymus development-related genes, PBX1 copy number gain and FOXC1 copy number loss were presented in 43.0% and 39.5% of the tumors, respectively. Immunohistochemistry on a series of 132 TETs, including those evaluated by comparative genomic hybridization, revealed a correlation between protein expression and copy number status only for FOXC1 but not for PBX1. Patients with FOXC1-negative tumors had a shorter time to progression and a trend for a shorter disease-related survival. The correlation between FOXC1 copy number loss and mRNA expression was confirmed in a separate cohort of 27 TETs. Ectopic FOXC1 expression attenuated anchorage-independent cell growth and cell migration in vitro. Conclusion: Our data support a tumor suppressor role of FOXC1 in TETs. Clin Cancer Res; 19(8); 1960–71. ©2013 AACR.
Iron-deficiency anaemia
Authors: D. Joshi, M. Rela, P. Rizzi, M. Heneghan, J. O'Grady, B. Portmann, J. O'Donohue
Journal: Gut (2007)

<b>Aim: </b>Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSAS) are two diseases that are characterized by obstruction of pulmonary airways. The aim of this study was to compare pulmonary function, functional exercise capacity and sleep quality in patients with COPD and OSAS. <b>Materials and methods: </b>Twenty-five COPD patients (21 M, 4 F) and 25 OSAS patients (16 M, 9 F) participated in the study. Pulmonary function were measured using a spirometer. Functional exercise capacity was evaluated using a six-minute walk test (6MWT). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). <b>Results: </b>Parameters of pulmonary function, 6MWT distance and %6MWT distance were significantly lower in patients with COPD than those of OSAS (p&lt;0.05). In patients with COPD, Borg dyspnea and fatigue were significantly increased and oxygen saturation was significantly decreased during 6MWT compared with OSAS patients (p&lt;0.05). The PSQI sleep duration score was significantly lower, and PSQI sleep disturbances and subjective sleep quality scores were significantly higher in patients with OSAS (p&lt;0.05). <b>Conclusion: </b>Pulmonary function and functional exercise capacity deteriorated in patients with COPD compared to OSAS patients. Exercise dyspnea and fatigue increases and oxygen saturation decreases in patients with COPD. In comparison with COPD patients, sleep duration and subjective sleep quality are adversely affected in patients with OSAS. Differences in sleep quality and exercise ratings in patients with OSAS may require special attention when implementing rehabilitation programs.
Renal Lesions Predict Progression of Diabetic Nephropathy in Type 1 Diabetes
Authors: M. Luiza Caramori, Alicia Parks, Michael Mauer
Journal: Journal of the American Society of Nephrology (2013)

Whether early glomerular, tubulointerstitial, vascular, and global glomerulosclerotic lesions can predict progression of diabetic nephropathy is not well defined. Here, we sought to determine whether renal structural parameters predict the development of proteinuria or ESRD after long-term follow-up. We measured several renal structures in kidney biopsies from 94 normoalbuminuric patients with longstanding type 1 diabetes using unbiased morphometric methods. Greater width of the glomerular basement membrane and higher levels of glycated hemoglobin were independent predictors of progression to diabetic nephropathy in this normoalbuminuric cohort. Moreover, none of these patients with type 1 diabetes who had glomerular basement membrane widths within the normal range developed proteinuria and/or ESRD. In conclusion, careful quantitative assessment of kidney biopsies in normoalbuminuric patients with type 1 diabetes adds substantially to the prediction of progression to clinical diabetic nephropathy.
Budesonide/formoterol maintenance and reliever therapy: impact on airway inflammation in asthma
Authors: M. R. Sears, L-P. Boulet, M. Laviolette, J. M. Fitzgerald, T. R. Bai, A. Kaplan, N. Smiljanic-Georgijev, J. S-M. Lee
Journal: European Respiratory Journal (2008)

The aim of the present study was to compare the effectiveness, safety and health economics of budesonide/formoterol maintenance and a novel reliever therapy with conventional best practice in patients with persistent asthma in Canada. After 2 weeks of usual therapy, 1,538 patients were randomised for 6 months to open-label budesonide/formoterol maintenance and reliever therapy 160/4.5 μg twice daily and as needed, or to guideline-based conventional best practice. Severe asthma exacerbations, reliever medication use and total inhaled corticosteroid dose were analysed in all patients and airway inflammation was assessed in a sub-study of 115 patients. No differences were seen in time to first severe exacerbation and severe asthma exacerbation rate. There were numerically fewer emergency room visits or hospitalisations with budesonide/formoterol maintenance and reliever therapy (4.4 versus 7.5 events per 100 patients·yr −1 , 41% reduction); however, this did not reach statistical significance. Mean total inhaled corticosteroid dose, reliever use, asthma medication costs and total annual costs per patient were all significantly lower with budesonide/formoterol maintenance and reliever therapy. Mean sputum eosinophil cell counts remained in the range for controlled inflammation in both groups. In conclusion, budesonide/formoterol maintenance and reliever therapy achieved similar or improved clinical control compared with conventional best practice, with significantly lower total inhaled corticosteroid dose and lower cost, while maintaining similar control of eosinophilic inflammation.
Supervised clustering of genes
Authors: Marcel Dettling, Peter Bühlmann
Journal: Genome biology (2002)

We focus on microarray data where experiments monitor gene expression in different tissues and where each experiment is equipped with an additional response variable such as a cancer type. Although the number of measured genes is in the thousands, it is assumed that only a few marker components of gene subsets determine the type of a tissue. Here we present a new method for finding such groups of genes by directly incorporating the response variables into the grouping process, yielding a supervised clustering algorithm for genes. An empirical study on eight publicly available microarray datasets shows that our algorithm identifies gene clusters with excellent predictive potential, often superior to classification with state-of-the-art methods based on single genes. Permutation tests and bootstrapping provide evidence that the output is reasonably stable and more than a noise artifact. In contrast to other methods such as hierarchical clustering, our algorithm identifies several gene clusters whose expression levels clearly distinguish the different tissue types. The identification of such gene clusters is potentially useful for medical diagnostics and may at the same time reveal insights into functional genomics.
Communication and Trust in the Care Provided to a Dying Parent: A Nationwide Study of Cancer-Bereaved Youths
Authors: Tove Bylund Grenklo, Ulrika C. Kreicbergs, Unnur A. Valdimarsdóttir, Tommy Nyberg, Gunnar Steineck, Carl Johan Fürst
Journal: Journal of Clinical Oncology (2013)

Purpose To assess children's trust in the care provided to a dying parent during the final week of life in relation to end-of-life medical information about disease, treatment, and death. Methods This nationwide population-based survey included 622 (73%) of 851 youths who, 6 to 9 years earlier, at age 13 to 16 years, lost a parent to cancer. We asked about the children's reception of end-of-life professional information and trust in the care provided. We also asked about depression and several potential risk factors of distrust in the care provided. Results A majority (82%) reported moderate/very much trust in the care provided. Compared with children who received end-of-life medical information before their loss, the risk of distrust in the care provided was higher in those who received no information (risk ratio [RR], 2.5; 95% CI, 1.5 to 4.1), in those who only received information afterward (RR, 3.2; 95% CI, 1.7 to 5.9), and in those who did not know or remember if end-of-life medical information was provided (RR, 1.7; 95% CI, 1.1 to 2.5). Those reporting distrust in the care provided had an RR of 2.3 (95% CI, 1.5 to 3.5) for depression. Furthermore, the risk of distrust in the care provided was higher among children reporting poor efforts to cure (RR, 5.1; 95% CI, 3.6 to 7.3), and/or a poor relationship with the surviving parent (RR, 2.9; 95% CI, 2.0 to 4.1). Conclusion Our study suggests that children's trust in the care provided to a dying parent was highest when they received end-of-life medical information before their loss.
Effect of Depo-Medroxyprogesterone Acetate on Breast Cancer Risk among Women 20 to 44 Years of Age
Authors: Christopher I. Li, Elisabeth F. Beaber, Mei Tzu Chen Tang, Peggy L. Porter, Janet R. Daling, Kathleen E. Malone
Journal: Cancer Research (2012)

Abstract Depo-medroxyprogesterone acetate (DMPA) is an injectable contraceptive that contains the same progestin as the menopausal hormone therapy regimen found to increase breast cancer risk among postmenopausal women in the Women's Health Initiative clinical trial. However, few studies have evaluated the relationship between DMPA use and breast cancer risk. Here, we conducted a population-based case–control study among 1,028 women ages 20 to 44 years to assess the association between DMPA use and breast cancer risk. Detailed information on DMPA use and other relevant covariates was obtained through structured interviewer-administered in-person questionnaires, and unconditional logistic regression was used to evaluate associations between various aspects of DMPA use and breast cancer risk. We found that recent DMPA use for 12 months or longer was associated with a 2.2-fold [95% confidence interval (CI), 1.2–4.2] increased risk of invasive breast cancer. This risk did not vary appreciably by tumor stage, size, hormone receptor expression, or histologic subtype. Although breast cancer is rare among young women and the elevated risk of breast cancer associated with DMPA appears to dissipate after discontinuation of use, our findings emphasize the importance of identifying the potential risks associated with specific forms of contraceptives given the number of available alternatives. Cancer Res; 72(8); 2028–35. ©2012 AACR.
Dehydroepiandrosterone sulphate in Alzheimer's disease
Authors: F. Leblhuber, E. Windhager, F. Reisecker, F.X. Steinparz, E. Dienstl, H. Cuckle, R. Stone, D. Smith, N. Wald, M. Brammer, I. Hajimohammedreza, R. Levy, T. Chard, L. Perry
Journal: The Lancet (1990)
Vomiting and a target sign on abdominal CT
Authors: C.-W. Chang, W.-S. Liao, S.-C. Shih, S.-C. Lin, T.-E. Wang, W.-H. Chang, J.-C. Lin
Journal: Gut (2008)

An 88-year-old woman was admitted with postprandial vomiting and fever for 2 days. She had had a subtotal gastrectomy with Billroth-II anastomosis for a gastric ulcer 30 years previously. For several months she …
Replacing smear microscopy for the diagnosis of tuberculosis: what is the market potential?
Authors: Sandra V. Kik, Claudia M. Denkinger, Pamela Chedore, Madhukar Pai
Journal: European Respiratory Journal (2014)

To the Editor: 

Sputum smear microscopy (SSM) has been the cornerstone of tuberculosis (TB) diagnosis, and is mainly performed in peripheral microscopy centres attached to primary health centres where TB therapy can be administered. Although SSM is inexpensive and easy to perform with a limited infrastructure, the shortcomings are its relatively low sensitivity and its inability to detect drug-resistance. Thus, there is a need for a more sensitive technology that can replace microscopy [1, 2].

Several next-generation molecular diagnostics are under development with the specific intention of use in microscopy centres [3–5]. In a recent survey of 22 high-burden countries (HBCs), we showed that the conditions, equipment and expertise present in microscopy centres are challenging and need to be considered by product developers [6]. While the Xpert MTB/RIF (Cepheid Inc., Sunnyvale, CA, USA) assay is accurate, endorsed by the World Health Organization and is being implemented in many countries, it was not designed for use in peripheral microscopy centres [7, 8]. To assist product developers working on tests for use in microscopy centres, we have outlined the desirable test characteristics [1].

For companies to take on the challenge and invest in new diagnostics, an understanding of the potential market size is paramount [9]. A 2006 global TB diagnostics market analysis predicted that a smear replacement test applied at the level of peripheral clinics and microscopy centres would have a potential market size of 36.6 million tests per year in the 22 HBCs in 2020, assuming it would diagnose pulmonary, extrapulmonary and paediatric TB [10 …
Reactor accidents. Public health strategies and their medical implications
Authors: D. V. Becker
Journal: JAMA (1987)

In a reactor accident with release of radioactivity, the major potential public health risks are likely to result from radioiodines, particularly iodine 131, which can be readily volatilized and dispersed. They are rapidly absorbed and concentrated by the thyroid, which could result in substantial thyroidal radiation. Although some forms of radiation can cause thyroid cancer in humans, 131I has not been shown to do so, and 40 years of safe experience with this radionuclide in routine clinical thyroid testing and treatment has been reassuring. Nevertheless, since 131I has been shown to cause thyroid neoplasms in animals, efforts to minimize unwarranted exposure seem advisable. Potassium iodide, administered at an appropriate time, will effectively block thyroid uptake, but it has potential toxicity and may be difficult to distribute effectively and safely on a large scale in an emergency. Evaluation of the risks and benefits of potassium iodide use is essential to establishing sound public health policy but awaits additional scientific information.
A novel role for Lef-1, a central transcription mediator of Wnt signaling, in leukemogenesis
Authors: Konstantin Petropoulos, Natalia Arseni, Christina Schessl, Christiane R. Stadler, Vijay P.S. Rawat, Aniruddha J. Deshpande, Bernhard Heilmeier, Wolfgang Hiddemann, Leticia Quintanilla-Martinez, Stefan K. Bohlander, Michaela Feuring-Buske, Christian Buske
Journal: The Journal of Experimental Medicine (2008)

Canonical Wnt signaling is critically involved in normal hematopoietic development and the self-renewal process of hematopoietic stem cells (HSCs). Deregulation of this pathway has been linked to a large variety of cancers, including different subtypes of leukemia. Lef-1 is a major transcription factor of this pathway and plays a pivotal role in lymphoid differentiation as well as in granulopoiesis. Here, we demonstrate Lef-1 expression in murine HSCs as well as its expression in human leukemia. Mice transplanted with bone marrow retrovirally transduced to express Lef-1 or a constitutive active Lef-1 mutant showed a severe disturbance of normal hematopoietic differentiation and finally developed B lymphoblastic and acute myeloid leukemia (AML). Lef-1–induced AMLs were characterized by immunoglobulin (Ig) DH-JH rearrangements and a promiscuous expression of lymphoid and myeloid regulatory factors. Furthermore, single cell experiments and limiting dilution transplantation assays demonstrated that Lef-1–induced AML was propagated by a leukemic stem cell with lymphoid characteristics displaying Ig DH-JH rearrangements and a B220+ myeloid marker− immunophenotype. These data indicate a thus far unknown role of Lef-1 in the biology of acute leukemia, pointing to the necessity of balanced Lef-1 expression for an ordered hematopoietic development.
Changes in hip fracture rate before and after total knee replacement due to osteoarthritis: a population-based cohort study
Authors: D. Prieto-Alhambra, M. K. Javaid, J. Maskell, A. Judge, M. Nevitt, C. Cooper, N. K. Arden
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> Patients with knee osteoarthritis have an increase in bone mass but no corresponding decrease in risk of fracture. This study describes the rates of hip fracture in subjects with knee osteoarthritis before and after having a total knee replacement (TKR), compared with matched controls. <h3>Methods</h3> A population-based prospective cohort study was conducted. The study population included, from the General Practice Research Database (UK), patients 40 years and older, undergoing TKR between 1986 and end-2006 for knee osteoarthritis as 'cases' (n=20 033). Five disease-free controls (n=100 165) were randomly selected, and matched for age, gender and practice. Hip fractures were ascertained using READ codes, and yearly rates of hip fracture and rate differences were calculated for the 5 years before and after surgery, using Poisson regression. Stratified analyses were performed by age and history of fracture. <h3>Results</h3> Hip fracture rates were non-significantly reduced compared with controls before the operation. In the year after TKR, risk increased significantly (RR 1.58; 95% CI 1.14 to 2.19). Rates then declined to equal those of controls by 3 years, and continued decreasing until the end of follow-up; corresponding RR were not significant. The increased risk is greatest in younger ages and in those without previous fracture. <h3>Conclusions</h3> The association between knee osteoarthritis and fractures is time-dependent, which may explain the current controversy in the literature. The association is also modified by TKR: subjects have a higher rate of hip fracture than matched controls after TKR, although the rates may eventually decrease.
JunB Induced by Constitutive CD30–Extracellular Signal-Regulated Kinase 1/2 Mitogen-Activated Protein Kinase Signaling Activates the CD30 Promoter in Anaplastic Large Cell Lymphoma and Reed-Sternberg Cells of Hodgkin Lymphoma
Authors: Mariko Watanabe, Masataka Sasaki, Kinji Itoh, Masaaki Higashihara, Kazuo Umezawa, Marshall E. Kadin, Lawrence J. Abraham, Toshiki Watanabe, Ryouichi Horie
Journal: Cancer Research (2005)

Abstract High expression of CD30 and JunB is characteristic of tumor cells in anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL). Possible interactions of CD30 and JunB were examined in this study. We found that the CD30 promoter in tumor cells of both nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)–positive and NPM-ALK-negative ALCL and HL is regulated by a constitutively active CD30–extracellular signal-regulated kinase (ERK) 1/2 mitogen-activated protein kinase (MAPK). Phosphorylation of ERK1/2 MAPK was confirmed in nuclei of tumor cells in both ALCL and HL. CD30-ERK1/2 MAPK signals induce JunB expression, which maintains high activity of the CD30 promoter. JunB induction seems to be largely independent of nuclear factor κB in ALCL and HL. These results show a common mechanism of CD30 overexpression in ALCL and HL, although the outcome of CD30 signaling differs between NPM-ALK-positive ALCL and NPM-ALK-negative ALCL, cutaneous ALCL, and HL as we recently reported.
Interleukin 1 Receptor Dependence of Serum Transferred Arthritis Can be Circumvented by Toll-like Receptor 4 Signaling
Authors: Jung-Yoon Choe, Brian Crain, Sarah R. Wu, Maripat Corr
Journal: The Journal of Experimental Medicine (2003)

Inflammatory arthritis is associated with the release of a network of key cytokines. In T cell receptor transgenic K/BxN mice interleukin (IL)-1 plays a key role in joint swelling and destruction, as suggested by the ability of anti–IL-1receptor (IL-1R) antibody treatment to delay the onset and slow the progression of this disease. This mechanism is dependent on the signaling pathway intermediary myeloid differentiation factor 88 (MyD88), such that neither IL-1R nor MyD88-deficient mice developed visually detectable synovitis after transfer of arthritogenic sera. The Toll-like receptors (TLRs) share the same signaling pathway through MyD88 as the IL-1R. The administration of a TLR-4 ligand, lipopolysaccharide, concomitant with arthritogenic serum in IL-1 receptor–deficient mice resulted in acute paw swelling, but not in MyD88-deficient mice. Also, serum transferred arthritis was not sustained in TLR-4 mutant mice compared with controls. These results suggest that innate immune functions via TLR-4 might perpetuate inflammatory mechanisms and bypass the need for IL-1 in chronic joint inflammation.
Distinct Patterns of Expression and Evolution of Intronless and Intron-Containing Mammalian Genes
Authors: Svetlana A. Shabalina, Aleksey Y. Ogurtsov, Alexey N. Spiridonov, Pavel S. Novichkov, Nikolay A. Spiridonov, Eugene V. Koonin
Journal: Molecular Biology and Evolution (2010)

Comparison of expression levels and breadth and evolutionary rates of intronless and intron-containing mammalian genes shows that intronless genes are expressed at lower levels, tend to be tissue specific, and evolve significantly faster than spliced genes. By contrast, monomorphic spliced genes that are not subject to detectable alternative splicing and polymorphic alternatively spliced genes show similar statistically indistinguishable patterns of expression and evolution. Alternative splicing is most common in ancient genes, whereas intronless genes appear to have relatively recent origins. These results imply tight coupling between different stages of gene expression, in particular, transcription, splicing, and nucleocytosolic transport of transcripts, and suggest that formation of intronless genes is an important route of evolution of novel tissue-specific functions in animals.
Pulmonary nodules due to reactive systemic amyloidosis (AA) in Crohn's disease.
Authors: T W Beer, C W Edwards
Journal: Thorax (1993)

Multiple nodules of AA (reactive systemic) amyloid were identified at necropsy in the lungs of a patient with Crohn9s disease. No other organs were involved. Nodular pulmonary amyloidosis is usually caused by deposition of AL (primary) amyloid.
Plasma concentrations and analgesic efficacy of lidocaine and prilocaine in leg ulcer‐related pain during daily application of lidocaine–prilocaine cream (<scp>EMLA</scp><sup>™</sup>) for 10 days
Authors: I. Effendy, A. Gelber, P. Lehmann, G. Huledal, S. Lillieborg
Journal: British Journal of Dermatology (2014)

Plasma concentrations and analgesic efficacy of lidocaine and prilocaine in leg ulcer-related pain during daily application of lidocaineprilocaine cream (EMLA TM ) for 10 days