tbuckley/cabot-search huggingface dataset:
Influence of atopy and asthma on exhaled nitric oxide in an unselected birth cohort study
Authors: M. Scott, A. Raza, W. Karmaus, F. Mitchell, J. Grundy, R. J Kurukulaaratchy, S H. Arshad, G. Roberts
Journal: Thorax (2010)

<h3>Background</h3> Asthma is considered to be associated with elevated levels of exhaled nitric oxide (FeNO). The nature of this relationship and how it is influenced by atopy are still not resolved. <h3>Methods</h3> The Isle of Wight birth cohort (N=1456) was reassessed at 18 years of age. Participants able to attend the research centre were assessed by questionnaires, skin prick testing and FeNO in order to explore the interrelationship between asthma, atopy and FeNO. <h3>Results</h3> Atopy was significantly associated with higher levels of FeNO. However, the level of FeNO for non-atopic asthmatic participants was no different to the non-atopic no-asthma group. The highest levels of FeNO were seen in subjects with both atopy and asthma. In addition, FeNO was positively associated with increasing atopic burden as evidenced by increasing FeNO with increasing skin prick testing positivity, and with increasing severity of atopic asthma as evidenced by the number of attacks of wheezing. FeNO and current inhaled corticosteroid use were not significantly associated. <h3>Conclusions</h3> FeNO behaves as a biomarker of atopy and the "allergic asthma" phenotype rather than asthma itself. This may explain why FeNO-guided asthma treatment outcomes have proved to be of limited success where atopic status has not been considered and accounted for.
Most α/β T Cell Receptor Diversity Is Due to Terminal Deoxynucleotidyl Transferase
Authors: Jean-Pierre Cabaniols, Nicolas Fazilleau, Armanda Casrouge, Philippe Kourilsky, Jean M. Kanellopoulos
Journal: The Journal of Experimental Medicine (2001)

The contribution of template-independent nucleotide addition to antigen receptor diversity is unknown. We therefore determined the size of the T cell receptor (TCR)alpha/beta repertoire in mice bearing a null mutation on both alleles of the terminal deoxynucleotidyl transferase (Tdt) gene. We used a method based upon polymerase chain reaction amplification and exhaustive sequencing of various AV-AJ and BV-BJ combinations. In both wild-type and Tdt degrees / degrees mice, TCRAV diversity is one order of magnitude lower than the TCRBV diversity. In Tdt degrees / degrees animals, TCRBV chain diversity is reduced 10-fold compared with wild-type mice. In addition, in Tdt degrees / degrees mice, one BV chain can associate with three to four AV chains as in wild-type mice. The alpha/beta repertoire size in Tdt degrees / degrees mice is estimated to be 10(5) distinct receptors, approximately 5-10% of that calculated for wild-type mice. Thus, while Tdt activity is not involved in the combinatorial diversity resulting from alpha/beta pairing, it contributes to at least 90% of TCRalpha/beta diversity.
Thrombomodulin and Tissue Factor Pathway Inhibitor in Endocardium of Rapidly Paced Rat Atria
Authors: Takeshi Yamashita, Akiko Sekiguchi, Yu-ki Iwasaki, Kouichi Sagara, Seiji Hatano, Hiroyuki Iinuma, Tadanori Aizawa, Long-Tai Fu
Journal: Circulation (2003)

Atrial fibrillation (AF) is well known as one of the cardiogenic causes for thromboembolism. Although decreased flow and hypercoagulable state of the blood in the fibrillating atrium have been emphasized as the underlying mechanisms, endocardial dysfunction in maintaining the local coagulation balance could also contribute to the thrombogenesis in AF.The paroxysmal AF model was created by rapid atrial pacing in anesthetized rats. To test the hypothesis that AF induces local coagulation imbalance by disturbing the atrial endocardial function, the gene expression of intrinsic anticoagulant factors, thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI), were determined by means of ribonuclease protection assay, Western blotting, and immunohistochemistry. Rapid atrial pacing for 8 hours significantly decreased TM and TFPI mRNA levels in the left atrium but not in the ventricle, leading to the downregulation of their immunoreactive proteins. Immunohistochemical analysis revealed that TM and TFPI were expressed predominantly in the endocardial cells of the normal atrium, presumably preventing local blood coagulation, and that rapid atrial pacing induced the loss of TM and TFPI expression in the endocardium, leading to deficiency in anticoagulant barriers between the atria and the blood.Rapid atrial pacing acutely downregulated the gene expression of TM and TFPI in the atrial endocardium, thereby inducing local coagulation imbalance on the internal surface of the atrial cavity. These results would support the validity of supplement of anticoagulant molecules deficient in AF.
Reasons for refusal of admission to intensive care and impact on mortality
Authors: Gaetano Iapichino, Davide Corbella, Cosetta Minelli, Gary H. Mills, Antonio Artigas, David L. Edbooke, Angelo Pezzi, Jozef Kesecioglu, Nicolò Patroniti, Mario Baras, Charles L. Sprung
Journal: Intensive Care Medicine (2010)
Human genomics and preparedness for infectious threats
Authors: Nicole F Dowling, Marta Gwinn, Alison Mawle
Journal: Genome Medicine (2009)

Public health preparedness requires effective surveillance of and rapid response to infectious disease outbreaks. Inclusion of research activities within the outbreak setting provides important opportunities to maximize limited resources, to enhance gains in scientific knowledge, and ultimately to increase levels of preparedness. With rapid advances in laboratory technologies, banking and analysis of human genomic specimens can be conducted as part of public health investigations, enabling valuable research well into the future.
Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years
Authors: Rolf Sauer, Torsten Liersch, Susanne Merkel, Rainer Fietkau, Werner Hohenberger, Clemens Hess, Heinz Becker, Hans-Rudolf Raab, Marie-Therese Villanueva, Helmut Witzigmann, Christian Wittekind, Tim Beissbarth, Claus Rödel
Journal: Journal of Clinical Oncology (2012)

Purpose Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months. Patients and Methods A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival. Results Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival. Conclusion There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.
One year change of knee cartilage morphology in the first release of participants from the Osteoarthritis Initiative progression subcohort: association with sex, body mass index, symptoms and radiographic osteoarthritis status
Authors: F Eckstein, S Maschek, W Wirth, M Hudelmaier, W Hitzl, B Wyman, M Nevitt, M-P Hellio Le Graverand
Journal: Annals of the Rheumatic Diseases (2008)

The Osteoarthritis Initiative (OAI) is a multicentre study targeted at identifying biomarkers for evaluating the progression and risk factors of symptomatic knee OA. Here cartilage loss using 3 Tesla (3 T) MRI is analysed over 1 year in a subset of the OAI, together with its association with various risk factors.An age- and gender-stratified subsample of the OAI progression subcohort (79 women and 77 men, mean (SD) age 60.9 (9.9) years, body mass index (BMI) 30.3 (4.7)) with both frequent symptoms and radiographic OA in at least one knee was studied. Coronal FLASHwe (fast low angle shot with water excitation) MRIs of the right knee were acquired at 3 T. Seven readers segmented tibial and femoral cartilages blinded to order of acquisition. Segmentations were quality controlled by one expert.The reduction in mean cartilage thickness (ThC) was greater (p = 0.004) in the medial than in the lateral compartment, greater (p = 0.001) in the medial femur (-1.9%) than in the medial tibia (-0.5%) and greater (p = 0.011) in the lateral tibia (-0.7%) than in the lateral femur (0.1%). Multifactorial analysis of variance did not reveal significant differences in the rate of change in ThC by sex, BMI, symptoms and radiographic knee OA status. Knees with Kellgren-Lawrence grade 2 or 3 and with a BMI >30 tended to display greater changes.In this sample of the OAI progression subcohort, the greatest, but overall very modest, rate of cartilage loss was observed in the weight-bearing medial femoral condyle. Knees with radiographic OA in obese participants showed trends towards higher rates of change than those of other participants, but these trends did not reach statistical significance.
Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism
Authors: Jing-jing Zhang, Yi-Yi Zhu, Kun-Ling Xie, Yun-Peng Peng, Jin-Qiu Tao, Jie Tang, Zheng Li, Ze-Kuan Xu, Cun-Cai Dai, Zhu-Yin Qian, Kui-Rong Jiang, Jun-Li Wu, Wen-Tao Gao, Qing Du, Yi Miao
Journal: Molecular Cancer (2014)

Increasing evidence indicates an important role of transcription factor Yin Yang-1 (YY1) in human tumorigenesis. However, its function in cancer remains controversial and the relevance of YY1 to pancreatic ductal adenocarcinoma (PDAC) remains to be clarified. In this study, we detected YY1 expression in clinical PDAC tissue samples and cell lines using quantitative RT-PCR, immunohistochemistry and western blotting. We also detected MUC4 and MMP10 mRNA levels in 108 PDAC samples using qRT-PCR and analyzed the correlations between YY1 and MUC4 or MMP10 expression. The role of YY1 in the proliferation, invasion and metastatic abilities of PDAC cells in vitro was studied by CCK-8 assay, cell migration and invasion assays. In vivo pancreatic tumor growth and metastasis was studied by a xenogenous subcutaneously implant model and a tail vein metastasis model. The potential mechanisms underlying YY1 mediated tumor progression in PDAC were explored by digital gene expression (DGE) sequencing, signal transduction pathways blockage experiments and luciferase assays. Statistical analysis was performed using the SPSS 15.0 software. We found that the expression of YY1 in PDACs was higher compared with their adjacent non-tumorous tissues and normal pancreas tissues. However, PDAC patients with high level overexpression of YY1 had better outcome than those with low level overexpression. YY1 expression levels were statistically negatively correlated with MMP10 expression levels, but not correlated with MUC4 expression levels. YY1 overexpression suppressed, whereas YY1 knockdown enhanced, the proliferation, invasion and metastatic properties of BXPC-3 cells, both in vitro and in vivo. YY1 suppresses invasion and metastasis of pancreatic cancer cells by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism. The present study suggested that YY1 plays a negative role, i.e. is a tumor suppressor, in PDAC, and may become a valuable diagnostic and prognostic marker of PDAC.
Obstructive sleep apnoea and oral breathing in patients free of nasal obstruction
Authors: I. Koutsourelakis, E. Vagiakis, C. Roussos, S. Zakynthinos
Journal: European Respiratory Journal (2006)

Although there is an association between nasal obstruction, oral breathing and obstructive sleep apnoea syndrome (OSAS), it remains unknown whether increased oral breathing occurs in patients with OSAS who are free of nasal obstruction. The present study evaluated the relationship between breathing route and OSAS in patients without nasal obstruction. The breathing route of 41 snorers (25 male; aged 26-77 yrs) with normal nasal resistance was examined during overnight polysomnography using a nasal cannula/pressure transducer and an oral thermistor. In total, 28 patients had OSAS (apnoeics) and 13 patients were simple snorers. Apnoeics had a higher percentage of oral and oro-nasal breathing epochs. Oral and oro-nasal breathing epochs were positively related with apnoea/hypopnoea index (AHI) and duration of apnoeas/hypopnoeas and inversely related to oxygen saturation. Additionally, oro-nasal breathing epochs correlated with body mass index (BMI). In multiple linear regression analysis, oral breathing epochs were independently related only to AHI (r2 = 0.443), and oro-nasal breathing epochs were independently related to AHI (r2 = 0.736) and BMI (r2 = 0.036). In conclusion, apnoeics spent more time breathing orally and oro-nasally than simple snorers, and the apnoea/hypopnoea index is a major determinant of the time spent breathing orally and oro-nasally.
Generic medical and surgical endoscopy training lists can improve the number of opportunities for training in colonoscopy
Authors: C. A. Lamb, J. N. Singh, M. Eltringham, J. A. Barbour
Journal: Gut (2011)

<h3>Introduction</h3> The Joint Advisory Group on GI endoscopy (JAG), advise that endoscopy units provide one training list per week per trainee. In late 2009 it was observed that insufficient opportunities for training were available in our unit to meet this criteria. This was thought to be as a result of trainees being attached to a single trainer, with subsequent cancellation of training lists due to on call commitments, annual leave and study leave. As a response, in early 2010 we introduced generic training lists where medical and surgical consultants would identify a defined number of endoscopy training lists they could offer each month. Trainees would then allocate themselves to lists according to their timetable, and as a consequence receive training and feedback from a variety of medical and surgical trainers. The aim of this study was to analyse the outcomes of this new training system. <h3>Methods</h3> An audit of the JETS eportfolio for the 5 colonoscopy trainees (3 medical and 2 surgical) within our unit, was undertaken to determine the number of training lists attended in the 4<sup>th</sup> quarter of 2009 prior to introducing generic training lists, and to compare this to the 2<sup>nd</sup> quarter of 2010 following commencement of the new system. Trainees were also asked to comment on their experience of the generic training lists. <h3>Results</h3> The results of the audit are summarised in table 1. There was an increase in the mean number of training lists from 7.8 per quarter to 13.6 per quarter per trainee as a result of the new system. This was associated with a mean increase in caecal intubation rate, number of procedures performed, and the number of Direct Observation of Procedural Skills (DOPS) forms completed for each trainee. Four of the five trainees felt that the variety of trainers in the new system was an advantage over being taught by one trainer. <h3>Conclusion</h3> The introduction of generic medical and surgical endoscopy training lists can improve the number of training lists available to trainees in accordance with JAG guidance. This may lead to improvement in trainee caecal intubation rates, and an increase in the amount of formal feedback provided by trainers.
<i>HER2</i> status and efficay of taxane-based adjuvant therapy of early breast cancer (EBC): a metanalysis of randomized trials involving 7,831 patients.
Authors: M De Laurentiis, C Criscitiello, A Giordano, M Giuliano, R Lauria, V Forestieri, A Montanino, S De Placido
Journal: Cancer Research (2009)

Abstract Abstract #707 Background. Taxanes have recently been introduced in the adjuvant treatment of EBC yielding on average an improvement of disease-free-survival (DFS) and overall survival (OS) as compared to anthracycline-based regimens (De Laurentiis et al., JCO 2008). It has been questioned, however, that this average benefit may be driven largely by improved outcome in a restricted subset of patients. Particularly, it has been suggested that only patients with HER2+ tumors may derive benefits from taxane administration (Pritchard et al. JCO 2008). We performed a meta-analysis on the interaction between HER2 status and the efficacy of adjuvant taxane-based therapy by pooling subsets data of the available randomized trials.&amp;#x2028; Methods. We searched the Pubmed database to identify randomized trials that compared taxane-based with non-taxane-based adjuvant chemotherapy regimens for EBC and reported efficacy data according to HER2 status. We also searched the proceedings of major international conferences to identify relevant trials with subset analyses. Hazard Hatios (HRs) for DFS were pooled across the studies according to HER2 status by inverse variance weighting. A pooled test for treatment by HER2 status interaction was performed by weighted linear meta-regression. All statistical tests were two-sided.&amp;#x2028; Results. Six studies were eligible for this analysis, accounting for 11,631 patients, of whom 7,831 had HER2 status information available. Overall, taxanes were superior to non-taxane-based regimens in terms of DFS with a pooled HR = 0.85 (95%CI: 0.77-0.93). At pooled subgroup analysis taxanes yielded a statistically significant DFS improvement both in HER2+ disease (n = 1,730), with a pooled HR = 0.78 (95% CI: 0.67 to 0.92; p= 0.004), and in HER2- disease (n = 6,101), with a pooled HR = 0.88 (95% CI = 0.79 to 0.98; p= 0.02). A test for interaction showed that there is no statistically-significant difference in the efficacy of taxane-based chemotherapy according to HER2 status (p=0.27).&amp;#x2028; &amp;#x2028; Discussion. There is no evidence of interaction between HER2 status and taxane efficacy in EBC. HER2 status should not be used to decide which patients are candidate to adjuvant taxane-based therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 707.
Salt depletion and hypoalbuminaemia in cystic fibrosis may add to hypercapnia in acute respiratory failure
Authors: S J Kelly
Journal: Thorax (2003)

▴ Holland AE, Wilson JW, Kotsimbos TC, et al . Metabolic alkalosis contributes to acute hypercapnic respiratory failure in adult cystic fibrosis. Chest2003;124:490–3 [OpenUrl][1][CrossRef][2][PubMed][3] Patients admitted over a 1 year period with acute exacerbations of cystic fibrosis (CF) and hypercapnia (Paco2 ⩾45 mm Hg, n=14) were compared with a control group with hypercapnic exacerbations of COPD (n=49). The CF group were significantly younger (23 v … [1]: {openurl}?query=rft.jtitle%253DChest%26rft.stitle%253DChest%26rft.issn%253D0012-3692%26rft.aulast%253DHolland%26rft.auinit1%253DA.%2BE.%26rft.volume%253D124%26rft.issue%253D2%26rft.spage%253D490%26rft.epage%253D493%26rft.atitle%253DMetabolic%2BAlkalosis%2BContributes%2Bto%2BAcute%2BHypercapnic%2BRespiratory%2BFailure%2Bin%2BAdult%2BCystic%2BFibrosis%26rft_id%253Dinfo%253Adoi%252F10.1378%252Fchest.124.2.490%26rft_id%253Dinfo%253Apmid%252F12907533%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1378/chest.124.2.490&link_type=DOI [3]: /lookup/external-ref?access_num=12907533&link_type=MED&atom=%2Fthoraxjnl%2F58%2F11%2F973.atom
Computational Models of the Neural Bases of Learning and Memory
Authors: Mark A. Gluck, Richard Granger
Journal: Annual Review of Neuroscience (1993)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Steroid Hormone Synthesis by Vaccinia Virus Suppresses the Inflammatory Response to Infection
Authors: Patrick C. Reading, Jeffrey B. Moore, Geoffrey L. Smith
Journal: The Journal of Experimental Medicine (2003)

The 3β-hydroxysteroid dehydrogenase (3β-HSD) isoenzymes play a key role in cellular steroid hormone synthesis. Vaccinia virus (VV) also synthesizes steroid hormones with a 3β-HSD enzyme (v3β-HSD) encoded by gene A44L. Here we examined the effects of v3β-HSD in VV disease using wild-type (vA44L), deletion (vΔA44L), and revertant (vA44L-rev) viruses in a murine intranasal model. Loss of A44L was associated with an attenuated phenotype. Early (days 1–3) after infection with vΔA44L or control viruses the only difference observed between groups was the reduced corticosterone level in lungs and plasma of vΔA44L-infected animals. Other parameters examined (body weight, signs of illness, temperature, virus titres, the pulmonary inflammatory infiltrate, and interferon [IFN]-γ levels) were indistinguishable between groups. Subsequently, vΔA44L-infected animals had reduced weight loss and signs of illness, and displayed a vigorous pulmonary inflammatory response. This was characterized by rapid recruitment of CD4+ and CD8+ lymphocytes, enhanced IFN-γ production and augmented cytotoxic T lymphocyte activity. These data suggest that steroid production by v3β-HSD contributes to virus virulence by inhibiting an effective inflammatory response to infection.
Whooping Cough — Viral or Bacterial Disease?
Authors: John D. Nelson
Journal: New England Journal of Medicine (1970)

In some despair Robert Watt wrote in 1813 that whooping cough "... has been very generally abandoned by the profession and left to the management of old women and quacks."1 The dwindling interest in the disease among physicians in the past generation lends some currency to this statement, although we should prefer to label the coterie of persistent pertussis investigators something other than quacks. It is, therefore, refreshing to see interest in this classic disease revivified by Connor's article in this issue of the Journal. Before Bordet and Gengou the small bacilli abundant in nasopharyngeal mucus and sputum from patients . . .