tbuckley/cabot-search huggingface dataset:
Genome mapping and expression analyses of human intronic noncoding RNAs reveal tissue-specific patterns and enrichment in genes related to regulation of transcription
Authors: Helder I Nakaya, Paulo P Amaral, Rodrigo Louro, André Lopes, Angela A Fachel, Yuri B Moreira, Tarik A El-Jundi, Aline M da Silva, Eduardo M Reis, Sergio Verjovski-Almeida
Journal: Genome biology (2007)

Abstract Background RNAs transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression. However, the complement of human genes in which introns are transcribed, and the number of intronic transcriptional units and their tissue expression patterns are not known. Results A survey of mRNA and EST public databases revealed more than 55,000 totally intronic noncoding (TIN) RNAs transcribed from the introns of 74% of all unique RefSeq genes. Guided by this information, we designed an oligoarray platform containing sense and antisense probes for each of 7,135 randomly selected TIN transcripts plus the corresponding protein-coding genes. We identified exonic and intronic tissue-specific expression signatures for human liver, prostate and kidney. The most highly expressed antisense TIN RNAs were transcribed from introns of protein-coding genes significantly enriched ( p = 0.002 to 0.022) in the 'Regulation of transcription' Gene Ontology category. RNA polymerase II inhibition resulted in increased expression of a fraction of intronic RNAs in cell cultures, suggesting that other RNA polymerases may be involved in their biosynthesis. Members of a subset of intronic and protein-coding signatures transcribed from the same genomic loci have correlated expression patterns, suggesting that intronic RNAs regulate the abundance or the pattern of exon usage in protein-coding messages. Conclusion We have identified diverse intronic RNA expression patterns, pointing to distinct regulatory roles. This gene-oriented approach, using a combined intron-exon oligoarray, should permit further comparative analysis of intronic transcription under various physiological and pathological conditions, thus advancing current knowledge about the biological functions of these noncoding RNAs.
Molecular Pathways: Involvement of Immune Pathways in the Therapeutic Response and Outcome in Breast Cancer
Authors: Fabrice Andre, Maria V. Dieci, Peter Dubsky, Christos Sotiriou, Giuseppe Curigliano, Carsten Denkert, Sherene Loi
Journal: Clinical Cancer Research (2012)

Abstract The immune system could mediate the antitumor activity of several anticancer treatments. Several chemotherapy compounds, including anthracyclines and oxaliplatin, induce immunogenic cell death that in turn activates antitumor immune response. Trastuzumab induces antibody-dependant cell-mediated cytotoxicity. On the basis of this background, immune markers have recently been the focus of intense translational research to predict and monitor the efficacy of treatments. Gene expression arrays and immunohistochemistry have assessed immune activation and infiltration by macrophages, natural killer, and T and B lymphocytes. Using these approaches, several retrospective analyses of large trials have shown that activation of immune pathway may predict treatment efficacy and outcome in patients with breast cancers. As examples, intratumoral infiltration by lymphocytes and interferon-response in primary tumor predicted the efficacy of neoadjuvant chemotherapy. Intratumoral infiltration by lymphocytes was associated with good prognosis in patients with triple-negative breast cancer treated with adjuvant chemotherapy. More recently, it has been suggested that lymphocyte infiltration could also predict efficacy of trastuzumab. Finally, small retrospective studies have suggested that postchemotherapy lymphocyte infiltrates could be associated with better outcome in patients who did not reach pathologic complete response. This body of evidence suggests that assessing immune infiltration and activation could be useful in the future to stratify breast cancer patients. In addition, they provide evidence for the development of immunotherapies in breast cancer patients. Clin Cancer Res; 19(1); 28–. ©2012 AACR.
The impact of meconium ileus on the clinical course of children with cystic fibrosis
Authors: A.K.C. Evans, D.A. Fitzgerald, K.O. McKay
Journal: European Respiratory Journal (2001)

The present study was designed to compare the clinical course of children diagnosed with cystic fibrosis (CF) in infancy due to the presence of meconium ileus (MI) with children diagnosed by way of a newborn screening programme (non-MI). A matched case-control study design was used. Matching was performed on the basis of sex and date of birth. All children born in New South Wales, Australia after 1980 and who had attended the CF clinic at The Children9s Hospital at Westmead since diagnosis were included as possible cases or controls. Parameters pertaining to the clinical course were compared in 39 matched pairs. MI children had a significantly worse pulmonary status. The forced expiratory volume in one second was 16.3±5.2% higher (p&lt;0.001, n=21 pairs) and the forced vital capacity value 10.5±4.7% higher (p&lt;0.05, n=21 pairs) in non-MI children. The difference between the pairs (18.6±4.4 MI and 20.5±3.4 non-MI) in the Shwachman chest radiograph score was statistically significant (p&lt;0.05, n=39 pairs). There were no significant differences in any other assessed parameters, such as height, weight, the presence of liver function abnormalities, the frequency of hospitalization or airway microbial colonization. Meconium ileus may be an early indication of a more severe phenotype of cystic fibrosis. This was suggested by the significantly lower pulmonary function found in children with a history of meconium ileus compared to age- and sex-matched children who did not have meconium ileus.
Weight loss associated with reduced intake of carbohydrate reduces the atherogenicity of LDL in premenopausal women
Authors: Ingrid Lofgren, Tosca Zern, Kristin Herron, Kristy West, Matthew J. Sharman, Jeff S. Volek, Neil S. Shachter, Sung I. Koo, Maria Luz Fernandez
Journal: Metabolism (2005)
A knowledge transfer scheme to bridge the gap between science and practice: an integration of existing research frameworks into a tool for practice
Authors: Evert Verhagen, Nelly Voogt, Anja Bruinsma, Caroline F Finch
Journal: British Journal of Sports Medicine (2013)

Evidence of effectiveness does not equal successful implementation. To progress the field, practical tools are needed to bridge the gap between research and practice and to truly unite effectiveness and implementation evidence. This paper describes the Knowledge Transfer Scheme integrating existing implementation research frameworks into a tool which has been developed specifically to bridge the gap between knowledge derived from research on the one side and evidence-based usable information and tools for practice on the other.
Vanilloid (Capsaicin) Receptors and Mechanisms
Authors: Arpad Szallasi, Peter M. Blumberg
Journal: Pharmacological Reviews (1999)

Natural products afford a window of opportunity to study important biology. If the natural product is used or abused by human beings, finding its biological target(s) is all the more significant. Hot pepper is eaten on a daily basis by an estimated one-quarter of the world’s population and
Therapy with nCPAP: incomplete elimination of Sleep Related Breathing Disorder
Authors: L Grote, J Hedner, R Grunstein, H Kraiczi
Journal: European Respiratory Journal (2000)

Correct assessment of the overall treatment effectiveness requires knowledge about therapy compliance and efficacy. This study aimed to determine overall long-term apnoea alleviation after continuous positive airway pressure (CPAP) in a complete sleep laboratory cohort. Out of 209 consecutive CPAP candidates (mean age 57+/-12 yrs, body mass index (BMI) 30.0+/-5.1 kg x m2, respiratory disturbance index (RDI) 32.9+/-29 h), follow-up treatment was performed in 149 of them at 9, 18 and 30 months after CPAP prescription. Compliance with CPAP (machine run time/days CPAP available) was adjusted for the individual subjective sleep-time. Apnoea alleviation was defined as adjusted compliance multiplied by the CPAP effect (RDI with CPAP applied), remaining RDI was calculated. The baseline RDI, age or BMI in 75 patients, who did not tolerate nasal continuous positive airway pressure (nCPAP), did not differ from those accepting CPAP (acceptors, n=74). In acceptors at 9 months follow-up RDI with CPAP applied was 1.4+/-2.6 (CPAP effect, n=66), mean CPAP use was 3.6+/-2.5 x 24 h(-1) (n=68), mean apnoea alleviation was 52.4+/-32.0% (range 1-100%, n=47), the average remaining whole-night RDI was 17.8+/-26. At 9, 18 and 30 months (n=47), the mean daily CPAP use increased from 3.6+/-2.5 h to 4.1+/-2.5 h and 4.4+/-2.4 h (p&lt;0.01). Effectiveness of continuous positive airway pressure is potentially high but acceptance was low. When accounting for sleep-time, its actual effect and use, only 50% adjusted continuous positive airway pressure effectiveness was observed.
PREDICTIVE TESTING FOR HUNTINGTON'S DISEASE WITH LINKED DNA MARKERS
Authors: DavidJ.H. Brock, Ann Curtis, Lilias Barron, Doreen Dinwoodie, Aileen Crosbie, Moira Mennie, F.A. Millan, J.A. Raeburn, Susan Holloway, Alan Wright, Ian Pullen
Journal: The Lancet (1989)
Inhibitory effect of a soluble transforming growth factor β type II receptor on the activation of rat hepatic stellate cells in primary culture
Authors: Xuezhi Cui, Ichiro Shimizu, Guangming Lu, Mina Itonaga, Hiroshi Inoue, Masayuki Shono, Katsuyoshi Tamaki, Hiroshi Fukuno, Hikaru Ueno, Susumu Ito
Journal: Journal of Hepatology (2003)
Tumor–ratio–metastasis staging system as an alternative to the 7th edition UICC TNM system in gastric cancer after D2 resection—results of a single-institution study of 1343 Chinese patients
Authors: W. Wang, D.Z. Xu, Y.F. Li, Y.X. Guan, X.W. Sun, Y.B. Chen, R. Kesari, C.Y. Huang, W. Li, Y.Q. Zhan, Z.W. Zhou
Journal: Annals of Oncology (2011)
Targeted Therapies in Non–Small-Cell Lung Cancer Management: No Cost-Effective Strategies?
Authors: Christos Chouaid, Isabelle Borget, Alain Vergnenegre
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: Using a Markov model and from the Canadian perspective, Dajlalov et al 1 reported the cost-effectiveness in advanced nonsquamous non–small-cell lung cancer (NSCLC) of EML4-ALK fusion testing in combination with targeted first-line crizotinib as well as the cost-effectiveness of first-line crizotinib compared with standard care in patients with known EML4-ALK positivity. The incremental costeffectiveness ratio (ICER) of these two strategies was Canadian $255,870 and $250,632, respecfively, per quality-adjusted life-year (QALY) gained, and the authors concluded that these strategies are not cost effective. Although the authors appropriately discussed the limitations of the study we have two general comments on this exciting topic. Modeling in economic analysis is a useful and a relevant way to obtain results in case when no head-to-head trials have been performed, but specific heed needs to be paid to the key assumptions supporting the model. In the analysis by Dajlalov et al, 1 the standardcare strategy was cisplatin-gemcitabine doublet as first-line therapy, with pemetrexed and erlotinib as second- and third-line therapies. But the recommendations for first-line treatment of nonsquamous NSCLC also included pemetrexed concurrently with cisplatin and as an alternative, according to patient choice, bevacizumab combined with a paclitaxel-carboplatin regimen. Maintenance with bevacizumab or pemetrexed and switch maintenance with pemetrexed until progression are also acceptable options. Taking these recommendations into account impacts the standard of care, especially in costs, which increase from Canadian $1,527 to nearly $8,000 per chemotherapy cycle when using pemetrexed or bevacizumab in the first-line as well the maintenance setting. Unfortunately, in the sensitivity analysis, the cost of standard-care chemotherapy was not tested. Even if only a small proportion of patients received these high-cost drugs, it will probably significantly impact the ICER of both tested strategies. We also have a general comment about the interpretation of the ICER and the discrepancy between our clinical experience with crizotinib in patients with EML4-ALK positive NCSLC and the disappointing results of the economic analysis. In fact, these results should be compared with the ICER of recent strategies for management in NSCLC. For nonsquamous NSCLC in the United States in first-line setting, 2 the ICER of treatment with a cisplatin-pemetrexed doublet compared with carboplatin-paclitaxel and the ICER of treatment with carboplatin-paclitaxel-bevacizumab compared with cisplatinpemetrexed were $178,613 and $300,000, respectively, per life-year gained (LYG)—approximately $340,000 and $566,000, respectively, per QALY. Using pemetrexed as maintenance therapy 3 compared with observation led to an ICER of $122,371 per LYG (approximately $230,000 per QALY). In second-line setting in Canada, the ICER for erlotinib treatment in the
Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes
Authors: Nora A. Barrett, Opu M. Rahman, James M. Fernandez, Matthew W. Parsons, Wei Xing, K. Frank Austen, Yoshihide Kanaoka
Journal: The Journal of Experimental Medicine (2011)

The innate signaling pathways for Th2 immunity activated by inhaled antigens are not well defined. We previously identified Dectin-2 as a receptor for glycans in allergen extracts from the house dust mite Dermatophagoides farinae (Df) that mediates cysteinyl leukotriene (cys-LT) generation from pulmonary CD11c+ cells and from GM-CSF-cultured bone marrow cells (BMCs(GM-CSF)). Using lentiviral knockdown of Dectin-2 in BMCs(GM-CSF) and adoptive transfer of Df-pulsed BMCs(GM-CSF) to sensitize naive mice, we now report that Dectin-2 is critical for the development of Df-elicited eosinophilic and neutrophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Sensitization with Df-pulsed BMCs(GM-CSF) from LTC(4) synthase (LTC(4)S)-deficient mice or type 1 cys-LT receptor (CysLT1R)-deficient mice demonstrated that both proteins were required for Df-elicited eosinophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Direct sensitization and challenge of Ltc4s-/- and Cysltr1-/- mice confirmed that cys-LTs mediate these parameters of Df-elicited Th2 pulmonary inflammation. Thus, the Dectin-2-cys-LT pathway is critical for the induction of Th2 immunity to a major allergen, in part through CysLT1R. These findings identify a previously unrecognized link between a myeloid C-type lectin receptor and Th2 immunity.
Limited Overlap Between Intermediate Hyperglycemia as Defined by A1C 5.7–6.4%, Impaired Fasting Glucose, and Impaired Glucose Tolerance
Authors: Tuula Saukkonen, Henna Cederberg, Jari Jokelainen, Mauri Laakso, Pirjo Härkönen, Sirkka Keinänen-Kiukaanniemi, Ulla Rajala
Journal: Diabetes Care (2011)

We compared the prevalences and overlap between intermediate hyperglycemia (IH), defined by a hemoglobin A(1c) (A1C) 5.7-6.4%, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT).Oral glucose tolerance test results and A1C measurements were evaluated as markers of IH in an unselected cohort of 486 nondiabetic adults from Finland.The overall prevalence of IH was 34%. Prevalences of isolated A1C 5.7-6.4%, IGT, and IFG were 8.0, 13.2, and 4.5%, respectively. Overlap between these three markers was uncommon. Isolated A1C 5.7-6.4% was associated with a higher BMI compared with isolated IFG and IGT and with a more adverse lipid profile compared with isolated IFG.Prevalence of isolated IH was high, with limited overlap between the definitions. Differences in cardiovascular disease risk factors were observed among the groups. This study demonstrates that an A1C of 5.7-6.4% detects, in part, different individuals with IH compared with IFG and IGT.
Chronic Atrioventricular Nodal Vagal Stimulation
Authors: Youhua Zhang, Hirotsugu Yamada, Steve Bibevski, Shaowei Zhuang, Kent A. Mowrey, Don W. Wallick, Seil Oh, Todor N. Mazgalev
Journal: Circulation (2005)

We have previously demonstrated that selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during atrial fibrillation (AF) in acute experiments. However, it is not known whether this approach could provide a long-term treatment in conscious animals. Thus, this study reports the first observations on the long-term efficacy and safety of this novel approach to control ventricular rate during AF in chronically instrumented dogs.In 18 dogs, custom-made bipolar patch electrodes were sutured to the epicardial AVN fat pad for delivery of selective AVN-VS by a subcutaneously implanted nerve stimulator (pulse width 100 micros or 1 ms, frequency 20 or 160 Hz, amplitude 6 to 10 V). Fast-rate right atrial pacing (600 bpm) was used to induce and maintain AF. ECG, blood pressure, and body temperature were monitored telemetrically. One week after the induction of AF, AVN-VS was delivered and maintained for at least 5 weeks. It was found that AVN-VS had a consistent effect on ventricular rate slowing (on average 45+/-13 bpm) over the entire period of observation. Echocardiography showed improvement of cardiac indices with ventricular rate slowing. AVN-VS was well tolerated by the animals, causing no signs of distress or discomfort.Beneficial long-term ventricular rate slowing during AF can be achieved by implantation of a nerve stimulator attached to the epicardial AVN fat pad. This novel concept is an attractive alternative to other methods of rate control and may be applicable in a selected group of patients.
101 TENOFOVIR DF (TDF) COMPARED TO EMTRICITABINE (FTC)/TDF IN HBeAg-POSITIVE, CHRONIC HEPATITIS B (CHB) VIRUSINFECTED PATIENTS IN THE IMMUNE TOLERANT (IT) PHASE
Authors: H.L. Chan, C.K. Chan, A.J. Hui, S. Chan, F. Poordad, T.-T. Chang, P. Mathurin, J.F. Flaherty, L. Lin, K. Kitrinos, G.M. Subramanian, J.G. McHutchison, S. Lee, E. Gane
Journal: Journal of Hepatology (2013)
Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults
Authors: K. Schroeder
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether over the counter cough medicines are effective for acute cough in adults. <b>Design:</b> Systematic review of randomised controlled trials. <b>Data sources:</b> Search of the Cochrane Acute Respiratory Infections Group specialised register, Cochrane Controlled Trials Register, Medline, Embase, and the UK Department of Health National Research Register in all languages. <b>Included studies:</b> All randomised controlled trials that compared oral over the counter cough preparations with placebo in adults with acute cough due to upper respiratory tract infection in ambulatory settings and that had cough symptoms as an outcome. <b>Results:</b> 15 trials involving 2166 participants met all the inclusion criteria. Antihistamines seemed to be no better than placebo. There was conflicting evidence on the effectiveness of antitussives, expectorants, antihistamine-decongestant combinations, and other drug combinations compared with placebo. <b>Conclusion:</b> Over the counter cough medicines for acute cough cannot be recommended because there is no good evidence for their effectiveness. Even when trials had significant results, the effect sizes were small and of doubtful clinical relevance. Because of the small number of trials in each category, the results have to be interpreted cautiously.
Estimation of Tamoxifen's Efficacy for Preventing the Formation and Growth of Breast Tumors
Authors: M. D. Radmacher, R. Simon
Journal: JNCI Journal of the National Cancer Institute (2000)

BACKGROUND: Several randomized clinical trials have tested the hypothesis that tamoxifen is effective in preventing breast cancer. The largest such trial, the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Trial (BCPT), reported a 49% reduction in risk of invasive breast cancer for the tamoxifen group. However, it is unclear whether the effect of tamoxifen in this trial was mainly due to prevention of newly forming tumors or to treatment of occult disease. METHODS: We used various tumor growth models (i.e., exponential and Gompertzian [growth limited by tumor size]) and a computer simulation to approximate the percentage of detected tumors that were initiated after study entry. Maximum likelihood techniques were then used to estimate separately the efficacy of tamoxifen in treating occult disease and in preventing the formation and growth of new tumors. RESULTS: Under the assumptions of most of the growth models, the trial was sufficiently long for substantial numbers of new tumors to form, grow, and be detected during the trial. With the Gompertzian model and all available incidence data from the BCPT, it was estimated that 60% (95% confidence interval [CI] = 40%-80%) fewer new tumors were detected in the tamoxifen group than in the placebo group. Likewise, 35% (95% CI= 6%-63%) fewer occult tumors were detected in the tamoxifen group. With this model, the estimated incidence rate of invasive breast cancer among women in the placebo group of the BCPT was 7.7 (95% CI = 6.6-8.9) per 1000 women per year. Similar results were obtained with three exponential tumor growth models. CONCLUSIONS: These results support the concept that tamoxifen reduced cancer incidence in the BCPT through both treatment of occult disease and prevention of new tumor formation and growth. However, data from prevention trials may never be sufficient to completely distinguish prevention of new tumor formation from treatment of occult disease.
Hepatitis B Virus and HLA Antigen Display in the Liver During Chronic Hepatitis B Virus Infection
Authors: Luis Montaño, Guido C. Miescher, Alison H. Goodall, Karl H. Wiedmann, George Janossy, Howard C. Thomas
Journal: Hepatology (1982)

An analysis of the expression of the histocompatibility antigens in the livers of patients with chronic hepatitis B virus infection and normal subjects has demonstrated an increased expression of HLA–A,B,C antigens on the hepatocytes of patients with a low level of viral replication (HBe antibody positive) as compared with patients who exhibit a high level of viral replication (HBe antigen positive) and controls. This increase in the expression of histocompatibility antigens on the hepatocytes was associated with a decrease in the membrane expression of viral antigens by the same cells. These differences in the density of HLA and viral antigen display may influence the efficiency of T–cell cytolysis of hepatitis B virus–infected hepatocytes.
Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation
Authors: Deborah C. Molrine, Joseph H. Antin, Eva C. Guinan, Robert J. Soiffer, Kristin MacDonald, Richard Malley, Frank Malinoski, Susan Trocciola, Marjorie Wilson, Donna M. Ambrosino
Journal: Blood (2003)