tbuckley/cabot-search huggingface dataset:
Quantitative assessment of chronic lung disease of infancy using computed tomography
Authors: E.E. Sarria, R. Mattiello, L. Rao, C.J. Tiller, B. Poindexter, K.E. Applegate, J. Granroth-Cook, C. Denski, J. Nguyen, Z. Yu, E. Hoffman, R.S. Tepper
Journal: European Respiratory Journal (2011)

The aims of this study were to determine whether infants and toddlers with chronic lung disease of infancy (CLDI) have smaller airways and lower lung density compared with full-term healthy controls. Multi-slice computed tomography (CT) chest scans were obtained at elevated lung volumes during a brief respiratory pause in sedated infants and toddlers; 38 CLDI were compared with 39 full-term controls. For CLDI subjects, gestational age at birth ranged from 25 to 29 weeks. Airway size was measured for the trachea and the next three to four generations into the right lower lobe; lung volumes and tissue density were also measured. The relationship between airway size and airway generation differed between the CLDI and full-term groups; the sizes of the first and second airway generations were larger in the shorter CLDI than in the shorter full-term subjects. The increased size in the airways in the CLDI subjects was associated with increasing mechanical ventilation time in the neonatal period. CLDI subjects had a greater heterogeneity of lung density compared with full-term subjects. Our results indicate that quantitative analysis of multi-slice CT scans at elevated volumes provides important insights into the pulmonary pathology of infants and toddlers with CLDI.
Constitutive patterns of gene expression regulated by RNA-binding proteins
Authors: Davide Cirillo, Domenica Marchese, Federico Agostini, Carmen Livi, Teresa Botta-Orfila, Gian Tartaglia
Journal: Genome biology (2014)

RNA-binding proteins regulate a number of cellular processes, including synthesis, folding, translocation, assembly and clearance of RNAs. Recent studies have reported that an unexpectedly large number of proteins are able to interact with RNA, but the partners of many RNA-binding proteins are still uncharacterized.We combined prediction of ribonucleoprotein interactions, based on catRAPID calculations, with analysis of protein and RNA expression profiles from human tissues. We found strong interaction propensities for both positively and negatively correlated expression patterns. Our integration of in silico and ex vivo data unraveled two major types of protein-RNA interactions, with positively correlated patterns related to cell cycle control and negatively correlated patterns related to survival, growth and differentiation. To facilitate the investigation of protein-RNA interactions and expression networks, we developed the catRAPID express web server.Our analysis sheds light on the role of RNA-binding proteins in regulating proliferation and differentiation processes, and we provide a data exploration tool to aid future experimental studies.
Strenuous endurance exercise: is more better for everyone? Our genes won't tell us
Authors: André La Gerche, David L Prior, Hein Heidbüchel
Journal: British Journal of Sports Medicine (2010)

<h3>Introduction</h3> Analysis of faecal calprotectin (FC) is a non-invasive method for differentiating IBS from IBD. As a screening test, a normal FC has been employed to support a diagnosis of IBS, thereby avoiding invasive endoscopy in the patient cohort. We sought to investigate the diagnostic yield on subsequent colonoscopy in patients with mildly elevated FC and lower GI symptoms. <h3>Methods</h3> Between November 2009 and November 2010, all patients with a FC value of 50–100 μg/g of stool (normal &lt;50) were identified from our FC database. All of the stool samples were prepared and analysed according to the manufacturer9s instructions (Bühlmann calprotectin ELISA kit). Patients were excluded from analysis if they were outwith the age range 16–50, had previous faecal calprotectin levels &gt;100 ug/g stool, were known cases of IBD, had a history of NSAID intake, positive stool cultures, or any "alarm" GI symptoms. A similar cohort was identified with age &amp; sex matched controls with FC values &lt;50 μg/g. All the patients who did not go on to have a complete colonoscopy were removed from further analysis. Patients9 records were analysed electronically using the NHS Great Glasgow &amp; Clyde Clinical Portal. <h3>Results</h3> 216 patients were identified with a FC of 50–100 μg/g. After exclusion criteria, 158 patients remained. Of these 82 underwent complete colonoscopy (mean age 36.7, M:F 1:2.2) which was abnormal in only six cases (three cases of a single adenoma&lt;10 mm, one diverticulosis, one helminth infection &amp; one non-specific acute inflammation). 280 patients were identified with a FC&lt;50 μg/g. After exclusion criteria, 176 patients remained. Of these 65 underwent complete colonoscopy (mean age 36.6, M:F 1:2.3) which was abnormal in only eight cases (six cases of non-specific acute inflammation, one adenoma &lt;10 mm &amp; one diverticulosis). The colonoscopy outcome data, as expected, demonstrated that the pathology rate was very low in both groups. There was no difference in the rate of pathology detection between to two groups (p=0.3) and an FC&lt;100 μg/g has an NPV of 88% to exclude any pathology or 100% for significant pathology (IBD, advanced adenoma or colonic carcinoma). <h3>Conclusion</h3> In our population, the diagnostic yield of colonoscopy in patients below the age of fifty with new lower GI symptoms and a mildly elevated FC is very low. If our data can be replicated in a prospective manner, we suggest that invasive colonoscopy can be safely avoided in this cohort and interval FC analysis may be more appropriate. <h3>Competing interests</h3> None declared.
Integrating post-genomic approaches as a strategy to advance our understanding of health and disease
Authors: Jing Tang, Chong Tan, Matej Orešic, Antonio Vidal-Puig
Journal: Genome Medicine (2009)

Following the publication of the complete human genomic sequence, the post-genomic era is driven by the need to extract useful information from genomic data. Genomics, transcriptomics, proteomics, metabolomics, epidemiological data and microbial data provide different angles to our understanding of gene-environment interactions and the determinants of disease and health. Our goal and our challenge are to integrate these very different types of data and perspectives of disease into a global model suitable for dissecting the mechanisms of disease and for predicting novel therapeutic strategies. This review aims to highlight the need for and problems with complex data integration, and proposes a framework for data integration. While there are many obstacles to overcome, biological models based upon multiple datasets will probably become the basis that drives future biomedical research.
Advances in the Treatment of Lupus Nephritis
Authors: Robert Zimmerman, Jai Radhakrishnan, Anthony Valeri, Gerald Appel
Journal: Annual Review of Medicine (2001)

▪ Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to the formation and deposition of immune complexes throughout the body, which are pathogenic for the disease. Different forms of glomerulonephritis can occur in patients with SLE and can contribute significantly to the associated morbidity and, ultimately, mortality from the disease. Over the past two decades, there have been significant strides in our understanding of the disease and in treatments that attempt to control the formation and deposition of anti-DNA auto-antibodies and immune complexes, as well as the subsequent inflammatory cascade mediated through various cellular and humoral pathways leading to progressive renal damage and end-stage renal disease. In this chapter, we review the current understanding of the pathogenesis and treatment of lupus nephritis in its various stages and discuss the experimental and human data regarding some of the potential newer forms of therapy. We discuss data regarding the use of steroids, azathioprine, cyclophosphamide, cyclosporine A, mycophenolate mofetil, gammaglobulin, plasmapheresis, LJP 394, flaxseed oil, bindarit, anti-CD40 ligand, and CTLA4Ig.
The Impact of HER2/<i>neu</i>Expression Level on Response to the E75 Vaccine: From U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02
Authors: Linda C. Benavides, Jeremy D. Gates, Mark G. Carmichael, Ritesh Patel, Jarrod P. Holmes, Matthew T. Hueman, Elizabeth A. Mittendorf, Dianna Craig, Alexander Stojadinovic, Sathibalan Ponniah, George E. Peoples
Journal: Clinical Cancer Research (2009)

HER2/neu, a source of immunogenic peptides, is expressed in >75% of breast cancer patients. We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression. Vaccine response based on HER2/neu expression level was analyzed.Patients were stratified by HER2/neu expression. Low expressors (n = 100) were defined as HER2/neu immunohistochemistry (IHC) 1(+) to 2(+) or fluorescence in situ hybridization < 2.0. Overexpressors (n = 51) were defined as IHC 3(+) or fluorescence in situ hybridization > or = 2.0. Additional analyses were done stratifying by IHC status (0-3(+)). Standard clinocopathlogic factors, immunologic response (in vivo delayed-type hypersensitivity reactions; ex vivo human leukocyte antigen A2:immunoglobulin G dimer assay), and clinical responses (recurrence; mortality) were assessed.Low-expressor (control, 44; vaccinated, 56) versus overexpressor patients (control, 22; vaccinated, 29) were assessed. Low expressors, overexpressors, and most IHC-status vaccinated groups responded immunologically. Vaccinated low-expressor patients had larger maximum immunologic responses compared with overexpressor patients (P = 0.04), and vaccinated IHC 1(+) patients had increased long-term immune response (P = 0.08). More importantly, compared with controls, low-expressor patients had a mortality reduction (P = 0.08). The largest decrease in mortality was seen in IHC 1(+) patients (P = 0.05). In addition, a subset of overexpressor patients (n = 7) received trastuzumab before vaccination, and this combination seems safe and immunologically beneficial.Most patients with various levels of HER2/neu expression responded immunologically and seemed to benefit from vaccination. The low expressors, specifically IHC 1(+) patients, had more robust immunologic responses and may derive the greatest clinical benefit from the E75 vaccine.
Increased epithelial uptake of protein antigens in the ileum of Crohn's disease mediated by tumour necrosis factor 
Authors: J D Soderholm
Journal: Gut (2004)

The exact nature of the epithelial barrier defect in Crohn's disease remains to be elucidated. Previously we showed increased permeability to proteins in ileal Crohn's disease. Our aims were to study if this barrier defect (a) involves endocytotic uptake of antigens and (b) is related to low grade inflammation not detectable by histology.Macroscopically normal segments of distal ileum of Crohn's disease patients (n = 10) were subgrouped into non-inflamed (histologically unaffected) and slightly inflamed tissues and studied in Ussing chambers, with normal ileal specimens from colon cancer patients (n = 9) as controls. Endocytotic uptake into enterocytes of the protein antigen horseradish peroxidase was assessed by measuring the area of horseradish peroxidase containing endosomes in electron photomicrographs. Mucosal tumour necrosis factor alpha (TNF-alpha) mRNA was quantified using real time polymerase chain reaction. For comparison, the effects of low doses of TNF-alpha on endosomal uptake of horseradish peroxidase were studied in cultured T84 cells grown on filter supports.The area of horseradish peroxidase containing endosomes was increased (p<0.001) in enterocytes of non-inflamed ileum of Crohn's disease (2.8 (0.7) mum(2)/300 mum(2)) compared with control ileum (0.6 (0.06)). In non-inflamed mucosa, a significant association between endosomal uptake and mucosal expression of TNF-alpha mRNA (p = 0.03) was found. Low concentrations of TNF-alpha (0.25-1.0 ng/ml) enhanced the endosomal uptake of horseradish peroxidase in polarised T84 cells, without affecting transepithelial electrical resistance.Our findings suggest increased endosomal uptake of antigens in ileal Crohn's disease that may be mediated by TNF-alpha. These data highlight the transcellular route of antigen uptake in barrier dysfunction and implicate the interaction between epithelial cells and the innate immune system in the development of mucosal inflammation.
Hepatitis E masquerading as drug-induced liver injury
Authors: Emerson Y. Chen, Karl Baum, William Collins, Arthur Löve, Michael Merz, Sigurdur Olafsson, Einar S. Björnsson, William M. Lee
Journal: Hepatology (2012)

The patient presented below gives us the opportunity to discuss challenges in the diagnosis of drug-induced liver injury in an era of increasing awareness of hepatitis E. (HEPATOLOGY 2012;)
The impact of face shield use on concussions in ice hockey: a multivariate analysis
Authors: B W Benson, M S Rose, W H Meeuwisse
Journal: British Journal of Sports Medicine (2002)

Objective: To identify specific risk factors for concussion severity among ice hockey players wearing full face shields compared with half face shields (visors). Methods: A prospective cohort study was conducted during one varsity hockey season (1997–1998) with 642 male ice hockey players (median age 22 years) from 22 teams participating in the Canadian Inter-University Athletics Union. Half of the teams wore full face shields, and half wore half shields (visors) for every practice and game throughout the season. Team therapists and doctors recorded on structured forms daily injury, participation, and information on face shield use for each athlete. The main outcome measure was any traumatic brain injury requiring assessment or treatment by a team therapist or doctor, categorised by time lost from subsequent participation and compared by type of face shield worn. Results: Players who wore half face shields missed significantly more practices and games per concussion (2.4 times) than players who wore full face shields (4.07 sessions (95% confidence interval (CI) 3.48 to 4.74) v 1.71 sessions (95% CI 1.32 to 2.18) respectively). Significantly more playing time was lost by players wearing half shields during practices and games, and did not depend on whether the athletes were forwards or defence, rookies or veterans, or whether the concussions were new or recurrent. In addition, players who wore half face shields and no mouthguards at the time of concussion missed significantly more playing time (5.57 sessions per concussion; 95% CI 4.40 to 6.95) than players who wore half shields and mouthguards (2.76 sessions per concussion; 95% CI 2.14 to 3.55). Players who wore full face shields and mouthguards at the time of concussion lost no playing time compared with 1.80 sessions lost per concussion (95% CI 1.38 to 2.34) for players wearing full face shields and no mouthguards. Conclusions: The use of a full face shield compared with half face shield by intercollegiate ice hockey players significantly reduced the playing time lost because of concussion, suggesting that concussion severity may be reduced by the use of a full face shield.
Long-Term Survival for Patients With Non–Small-Cell Lung Cancer With Intratumoral Lymphoid Structures
Authors: Marie-Caroline Dieu-Nosjean, Martine Antoine, Claire Danel, Didier Heudes, Marie Wislez, Virginie Poulot, Nathalie Rabbe, Ludivine Laurans, Eric Tartour, Luc de Chaisemartin, Serge Lebecque, Wolf-Herman Fridman, Jacques Cadranel
Journal: Journal of Clinical Oncology (2008)

Purpose It has been established that the immune system plays an important role in tumor rejection. There is also compelling evidence that immune responses can develop independently of secondary lymphoid organs in tertiary lymphoid structures. We studied the presence and the correlation of tertiary lymphoid structures with clinical outcome in non–small-cell lung cancer (NSCLC), as the prognostic value of these structures in patients with cancer had not yet been established. Patients and Methods This retrospective study was performed by immunohistochemistry on paraffin-embedded tissue specimens from 74 patients with early-stage NSCLC. Results Tertiary lymphoid structures were detected in some tumors but not in nontumoral lungs. Thus we called these structures tumor-induced bronchus-associated lymphoid tissue (Ti-BALT). As in lymph nodes, Ti-BALTs were composed of mature dendritic cell (DC)/T-cell clusters adjacent to B-cell follicles and had features of an ongoing immune response. Because the quantitative counting of Ti-BALT was difficult to achieve, we used mature DCs that homed exclusively in Ti-BALT as a specific marker of these structures. Univariate analysis showed that the density of mature DCs was highly associated with a favorable clinical outcome (overall, disease-specific, and disease-free survival), suggesting that Ti-BALT may participate in antitumoral immunity. The density of tumor-infiltrating lymphocytes, in particular, CD4 + and T-bet + Th1 T cells, was profoundly decreased in tumors weakly infiltrated by mature DCs. Conclusion The density of mature DCs was found to be a better predictor of clinical outcome than the other parameters tested. The number of tumor-infiltrating mature DCs may identify patients with early-stage NSCLC who have a high risk of relapse.
T cell clones with dual specificity for M1s and various major histocompatibility complex determinants.
Authors: S R Webb, K Molnar-Kimber, J Bruce, J Sprent, D B Wilson
Journal: The Journal of Experimental Medicine (1981)

A high proportion of T cell clones derived from bulk cultures selected to M1s a,d determinants were found to have joint specificity for allo-H-2 determinants, and vice versa. Significantly, the patterns of H-2 alloreactivity shown by clones selected to M1sa,b determinants appeared to be random. The possible implications of these findings are discussed.
Evaluation of retinoic acid therapy for OTX2-positive medulloblastomas
Authors: Renyuan Bai, I-Mei Siu, Betty M. Tyler, Verena Staedtke, Gary L. Gallia, Gregory J. Riggins
Journal: Neuro-Oncology (2010)

The homeobox transcription factor OTX2 plays an essential role during embryonic brain development. It is normally silenced in the adult brain, but is overexpressed by genomic amplification or other mechanisms in the majority of medulloblastomas (MBs). Retinoic acids (RAs) can suppress OTX2 expression and inhibit MB growth. In this study, 9-cis RA most potently inhibited MB cell growth. 9-cis RA functions through the downregulation of OTX2 expression, which subsequently induces neuronal differentiation of OTX2-expressing cells. Treatment with 9-cis RA reduced the growth of D425 flank xenograft tumors in mice. In an intracranial model, however, MB tumors showed resistance to 9-cis RA treatment, and we implicated fibroblast growth factor (FGF) as a potential mediator of resistance to RA therapy. These findings suggest a mechanism for RA-mediated anti-tumor effect on OTX2-positive MB cells and indicate that therapeutic targeting of OTX2 might be effective if FGF pathway-mediated resistance can be overcome.
Osteopontin and Periostin Are Associated with a 20-Year Decline of Pulmonary Function in Patients with Asthma
Authors: Yoshihiro Kanemitsu, Isao Ito, Akio Niimi, Kenji Izuhara, Shoichiro Ohta, Junya Ono, Toshiyuki Iwata, Hisako Matsumoto, Michiaki Mishima
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation
Authors: D G Wyse, A L Waldo, J P DiMarco, M J Domanski, Y Rosenberg, E B Schron, J C Kellen, H L Greene, M C Mickel, J E Dalquist, S D Corley
Journal: New England Journal of Medicine (2002)

There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended.
E4F1 deficiency results in oxidative stress–mediated cell death of leukemic cells
Authors: Elodie Hatchi, Genevieve Rodier, Matthieu Lacroix, Julie Caramel, Olivier Kirsh, Chantal Jacquet, Emilie Schrepfer, Sylviane Lagarrigue, Laetitia Karine Linares, Gwendaline Lledo, Sylvie Tondeur, Pierre Dubus, Claude Sardet, Laurent Le Cam
Journal: The Journal of Experimental Medicine (2011)

The multifunctional E4F1 protein was originally discovered as a target of the E1A viral oncoprotein. Growing evidence indicates that E4F1 is involved in key signaling pathways commonly deregulated during cell transformation. In this study, we investigate the influence of E4F1 on tumorigenesis. Wild-type mice injected with fetal liver cells from mice lacking CDKN2A, the gene encoding Ink4a/Arf, developed histiocytic sarcomas (HSs), a tumor originating from the monocytic/macrophagic lineage. Cre-mediated deletion of E4F1 resulted in the death of HS cells and tumor regression in vivo and extended the lifespan of recipient animals. In murine and human HS cell lines, E4F1 inactivation resulted in mitochondrial defects and increased production of reactive oxygen species (ROS) that triggered massive cell death. Notably, these defects of E4F1 depletion were observed in HS cells but not healthy primary macrophages. Short hairpin RNA–mediated depletion of E4F1 induced mitochondrial defects and ROS-mediated death in several human myeloid leukemia cell lines. E4F1 protein is overexpressed in a large subset of human acute myeloid leukemia samples. Together, these data reveal a role for E4F1 in the survival of myeloid leukemic cells and support the notion that targeting E4F1 activities might have therapeutic interest.
Comparison of three different sit and reach tests for measurement of hamstring flexibility in female university students
Authors: G Baltaci, N Un, V Tunay, A Besler, S Gerçeker
Journal: British Journal of Sports Medicine (2003)

The sit and reach test is the most common flexibility test used in health related fitness test batteries.To examine and compare three different sit and reach tests as a measure of hamstring flexibility in 102 female students.The traditional sit and reach test, the chair sit and reach test, the back saver sit and reach test, and passive straight leg raise were administered in three trials to all 102 students (mean (SD) age 22 (1) years) on the same day.A Pearson correlation coefficient analysis was significant (p<0.01) for the traditional sit and reach test with back saver sit and reach test and flexibility of hamstrings (r = 0.45 and 0.65 for left and right legs, and 0.63 and 0.53 for left and right legs respectively). Also, the back saver sit and reach test for the left (p<0.01) and right (p<0.05) leg was significantly associated with hamstring flexibility (r = 0.37 and 0.25 for the left leg and 0.50 and 0.44 for the right leg respectively).The results indicate that the back saver sit and reach test produces reasonably accurate and stable measures of hamstring flexibility. Moreover, it appears that this test is a safe and acceptable alternative to the traditional and chair sit and reach tests as a measure of hamstring flexibility in young women.