tbuckley/cabot-search huggingface dataset:
An Associate Editor's view
Authors: P D Sly
Journal: Thorax (2003)

Ultrastructural examination of bronchial specimens from children with moderate asthmaWe have read the paper by Çokug ˘ras ¸and colleagues on bronchial biopsies in asthmatic children with great concern. 1 These authors performed a study in asthmatic children in which prophylactic medication was discontinued for 1 month before a bronchoscopic examination which was performed solely as a research procedure.The Royal College of Paediatricians and Child Health states that "High risk procedures such as lung or liver biopsy, arterial puncture, and cardiac catheterization are not justified for research purposes alone.They should be carried out only when research is combined with diagnosis or treatment intended to benefit the child concerned". 2 Other authorities state that "Non-therapeutic research is particularly difficult to defend in moral terms when undertaken on children". 3 The risks of rigid bronchoscopy are surely no less than an arterial puncture, and discontinuing presumably necessary medication could only increase those risks.How can such a study possibly be justified by the authors or their ethics committee, and how can the Editors of a reputable journal possibly justify the publication of such a study?That the science is valuable is unquestionable, even though the use of more sophisticated pathological techniques would have enhanced it; but the scientific value by no means justifies the disregard of ethical principles.A journal such as Thorax should know better, particularly in the light of the scholarly and ethical review in the very same issue.
Nrf2 and Keap1 Abnormalities in Non–Small Cell Lung Carcinoma and Association with Clinicopathologic Features
Authors: Luisa M. Solis, Carmen Behrens, Wenli Dong, Milind Suraokar, Natalie C. Ozburn, Cesar A. Moran, Alejandro H. Corvalan, Shyam Biswal, Stephen G. Swisher, B. Nebiyou Bekele, John D. Minna, David J. Stewart, Ignacio I. Wistuba
Journal: Clinical Cancer Research (2010)

To understand the role of nuclear factor erythroid-2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in non-small cell lung cancer (NSCLC), we studied their expression in a large series of tumors with annotated clinicopathologic data, including response to platinum-based adjuvant chemotherapy.We determined the immunohistochemical expression of nuclear Nrf2 and cytoplasmic Keap1 in 304 NSCLCs and its association with patients' clinicopathologic characteristics, and in 89 tumors from patients who received neoadjuvant (n = 26) or adjuvant platinum-based chemotherapy (n = 63). We evaluated NFE2L2 and KEAP1 mutations in 31 tumor specimens.We detected nuclear Nrf2 expression in 26% of NSCLCs; it was significantly more common in squamous cell carcinomas (38%) than in adenocarcinomas (18%; P < 0.0001). Low or absent Keap1 expression was detected in 56% of NSCLCs; it was significantly more common in adenocarcinomas (62%) than in squamous cell carcinomas (46%; P = 0.0057). In NSCLC, mutations of NFE2L2 and KEAP1 were very uncommon (2 of 29 and 1 of 31 cases, respectively). In multivariate analysis, Nrf2 expression was associated with worse overall survival [P = 0.0139; hazard ratio (HR), 1.75] in NSCLC patients, and low or absent Keap1 expression was associated with worse overall survival (P = 0.0181; HR, 2.09) in squamous cell carcinoma. In univariate analysis, nuclear Nrf2 expression was associated with worse recurrence-free survival in squamous cell carcinoma patients who received adjuvant treatment (P = 0.0410; HR, 3.37).Increased expression of Nrf2 and decreased expression of Keap1 are common abnormalities in NSCLC and are associated with a poor outcome. Nuclear expression of Nrf2 in malignant lung cancer cells may play a role in resistance to platinum-based treatment in squamous cell carcinoma.
Origin, trafficking, and intraepithelial fate of gut-tropic T cells
Authors: Delphine Guy-Grand, Pierre Vassalli, Gerard Eberl, Pablo Pereira, Odile Burlen-Defranoux, Fabrice Lemaitre, James P. Di Santo, Antonio A. Freitas, Ana Cumano, Antonio Bandeira
Journal: The Journal of Experimental Medicine (2013)

The small intestine epithelium (SI-Ep) harbors millions of unconventional (γδ and CD4− CD8− NK1.1− TCRαβ) and conventional (CD8αβ and CD4) T cells, designated intraepithelial lymphocytes (IELs). Here, we identified the circulating pool of SI-Ep–tropic T cells and studied their capacity to colonize the SI-Ep under steady-state conditions in SPF mice. Developmentally regulated levels of α4β7 endowed recent thymic emigrants (RTEs) of unconventional types with higher SI-Ep tropism than their conventional homologues. SI-Ep–tropic RTEs, which in all lineages emerged naive, homed to the SI-Ep, but this environment was inadequate to stimulate them to cycle. In contrast, conventional and, unexpectedly, unconventional T cells, particularly Vγ7+ (hallmark of γδ IELs), previously stimulated to cycle in the gut-associated lymphoid tissue (GALT), proliferated in the SI-Ep. Cycling unconventional SI-Ep immigrants divided far more efficiently than their conventional homologues, thereby becoming predominant. This difference impacted on acquisition of high Granzyme B content, which required extensive proliferation. In conclusion, SI-Ep–tropic T cells follow a thymus–SI-Ep or a GALT–SI-Ep pathway, the latter generating highly competitive immigrants that are the sole precursors of cytotoxic IELs. These events occur continuously as part of the normal IEL dynamics.
An Official American Thoracic Society Statement: Work-Exacerbated Asthma
Authors: Paul K. Henneberger, Carrie A. Redlich, David B. Callahan, Philip Harber, Catherine Lemière, James Martin, Susan M. Tarlo, Olivier Vandenplas, Kjell Torén
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Occupational exposures can contribute to the exacerbation as well as the onset of asthma. However, work-exacerbated asthma (WEA) has received less attention than occupational asthma (OA) that is caused by work.The purpose of this Statement is to summarize current knowledge about the descriptive epidemiology, clinical characteristics, and management and treatment of WEA; propose a case definition for WEA; and discuss needs for prevention and research.Information about WEA was identified primarily by systematic searches of the medical literature. Statements about prevention and research needs were reached by consensus.WEA is defined as the worsening of asthma due to conditions at work. WEA is common, with a median prevalence of 21.5% among adults with asthma. Different types of agents or conditions at work may exacerbate asthma. WEA cases with persistent work-related symptoms can have clinical characteristics (level of severity, medication needs) and adverse socioeconomic outcomes (unemployment, reduction in income) similar to those of OA cases. Compared with adults with asthma unrelated to work, WEA cases report more days with symptoms, seek more medical care, and have a lower quality of life. WEA should be considered in any patient with asthma that is getting worse or who has work-related symptoms. Management of WEA should focus on reducing work exposures and optimizing standard medical management, with a change in jobs only if these measures are not successful.WEA is a common and underrecognized adverse outcome resulting from conditions at work. Additional research is needed to improve the understanding of the risk factors for, and mechanisms and outcomes of, WEA, and to inform and evaluate preventive interventions.
Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-κB with antimyeloma activity in vitro and in vivo
Authors: Rodger E. Tiedemann, Jessica Schmidt, Jonathan J. Keats, Chang-Xin Shi, Yuan Xiao Zhu, Stephen E. Palmer, Xinliang Mao, Aaron D. Schimmer, A. Keith Stewart
Journal: Blood (2008)
Outcomes for multidrug-resistant tuberculosis patients with and without resistance to fluoroquinolones and second-line injectable drugs: A meta-analysis of individual patient data
Authors: G.B. Migliori, S. Ahuja, D. Ashkin, M. Avendano, R. Banerjee, M. Bauer, J. Bayona, M. Becerra, A. Benedetti, M. Burgos, R. Centis, E.D. Chan, C.-Y. Chiang, H. Cox, L. D'Ambrosio, K. DeRiemer, N.H. Dung, D. Enarson, K. Flanagan, J. Flood, M.L. Garcia-Garcia, N. Gandhi, R. Granich, M.G. Hollm-Delgado, T.H. Holtz, M. Iseman, L. Jarlsberg, S. Keshavjee, H.R. Kim, W.-J. Koh, J. Lancaster, C. Lange, W.C.M. de Lange, V. Leimane, C.C. Leung, J. Li, S. Mishustin, C. Mitnick, M. Narita, P. O'Riordan, M. Pai, D. Palmero, S.K. Park, G. Pasvol, J. Pena, C. Pérez-Guzmán, M. Quelapio, A. Ponce-de-Leon, V. Riekstina, J. Robert, S. Royce, H.S. Schaaf, K.J. Seung, L. Shah, T.S. Shim, S.S. Shin, Y. Shiraishi, J. Sifuentes-Osornio, G. Sotgiu, M.J. Strand, P. Tabarsi, T.E. Tupasi, R. van Altena, M. Van der Walt, T.S. Van der Werf, M.H. Vargas, P. Viiklepp, J. Westenhouse, W.W. Yew, J.J. Yim, D. Menzies
Journal: European Respiratory Journal (2012)

Poor treatment outcomes have been reported for tuberculosis (TB) patients harbouring strains resistant to isoniazid and rifampicin (multidrug resistance or MDR-TB), fluoroquinolones and/or second-line injectable drugs.  We undertook a meta-analysis for response to treatment using individual data for MDR-TB patients whose strains had additional resistance to fluoroquinolones (MDR-TB+FQ), second-line injectables (MDR-TB+Inj) or both (extensive drug resistance; XDR-TB) including demographic and clinical details, treatment regimens, and outcomes.  26 centres provided data for 424 MDR-TB+FQ, 1129 MDR-TB+Inj, 405 XDR-TB, and 4776 other MDR-TB patients susceptible to FQ and Inj. Success was lower in MDR-TB+FQ (adjusted OR=0.6 [95%CL 0.5-0.7]) and XDR-TB patients (0.4 [0.3-0.6]) than in those with MDR-TB+Inj (0.8 [0.7-0.9]) and those with MDR-TB and no additional resistance (reference). No single drug was significantly associated with treatment success in MDR-TB+FQ and XDR-TB patients. In XDR-TB patients, success was highest if at least 6 drugs were used in the intensive phase (4.9 [1.4-16.6]) and 4 in the continuation phase (6.1[1.4-26.3]).  Study results suggest that regimens of a similar duration to those recommended in MDR-TB patients but containing more drugs achieve better results in XDR-TB patients. As all data in the analysis were from observational studies, bias may be substantial and better quality evidence will be needed to guide the optimization of regimens.
Reference values for lung function: past, present and future
Authors: S. Stanojevic, A. Wade, J. Stocks
Journal: European Respiratory Journal (2010)

Reliable interpretation of pulmonary function results relies on the availability of appropriate reference data to help distinguish between health and disease and to assess the severity and nature of any functional impairment. The overwhelming number of published reference equations, with at least 15 published for spirometry alone in the past 3 yrs, complicates the selection of an appropriate reference. The use of inappropriate reference equations and misinterpretation, even when potentially appropriate equations are used, can lead to serious errors in both under and over diagnosis, with its associated burden in terms of financial and human costs. Further misdiagnosis occurs when fixed cut-offs, such as 80% predicted forced expiratory volume in 1 s (FEV 1 ) or 0.70 FEV 1 /forced vital capacity, are used; particularly in young children and elderly adults. While per cent predicted has historically been used to interpret lung function results, z-scores are more appropriate as they take into account the predicted value, as well as the between-subject variability of measurements. We aim to highlight some of the main issues in selecting and using reference equations and discuss how recent developments may improve interpretation of pulmonary function results.
Prevalence and socioeconomic associations of asthma and allergic rhinitis in nothern Africa
Authors: V. Georgy, H. I. Fahim, M. El Gaafary, S. Walters
Journal: European Respiratory Journal (2006)

The aims of the current study were to ascertain the prevalence of asthma and allergic rhinoconjunctivitis symptoms in Cairo, Egypt (northern Africa), and to elucidate the socioeconomic factors associated with symptom prevalence and severity. A translated and adapted version of the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was distributed to a sample of 2,645 11-15-yr-olds in state and fee-paying schools in Cairo. The overall prevalences of wheeze ever, wheeze during the last year and physician-diagnosed asthma were 26.5% (697 out of 2,631), 14.7% (379 out of 2,570) and 9.4% (246 out of 2,609), respectively. The prevalence of rhinoconjunctivitis was 15.3% (399 out of 2,616). Asthma symptoms were independently associated with attendance at a state school, parental asthma, age, history of rhinitis and owning a pet cat. Rhinoconjunctivitis was independently associated with attendance at a state school, father's education, parental history of asthma, asthma symptoms and owning a pet cat. In spite of a higher prevalence of severe asthma symptoms in state schools prevalence of physician diagnosis of asthma was the same in both school types, suggesting inequalities in access to healthcare. In conclusion, the prevalence of physician-diagnosed asthma in Cairo was 9.4%, while the prevalence of rhinoconjunctivitis was 15.3%. There is a higher prevalence and increased severity of asthma symptoms in children of lower socioeconomic groups, as defined by state school attendance in Cairo.
Action of Manganese Ions and Tetrodotoxin on Atrioventricular Nodal Transmembrane Potentials in Isolated Rabbit Hearts
Authors: DOUGLAS P. ZIPES, CARLOS MENDEX
Journal: Circulation Research (1973)

In the isolated rabbit heart, it was shown that (1) manganese ions (Mn 2+ ) (2-4 m M ) suppressed the activity of atrioventricular (AV) nodal cells located in the AN, N, and NH regions without preventing regenerative responses in atrial or His bundle fibers when these fibers were directly stimulated, (2) tetrodotoxin (TTX) in concentrations of 5 x 10 -6 g/ml Tyrode's solution rendered atrial and His bundle fibers inexcitable without preventing AV nodal potentials of automatic origin and without affecting the rate of rise of cells located in the N region, and (3) in the presence of TTX (5 x l0 -6 g/ml of Tyrode's solution) the addition of epinephrine (2 µg/ml solution) restored atrial activity. It was concluded that the different effects of Mn 2+ and TTX on AV nodal action potentials is consistent with the postulate, made by Rougier et al. (8) and Vassort et al. (9) for frog atrial fibers treated with TTX, that AV nodal action potentials probably result from the operation of a slow ionic channel.
On the role of frame-based knowledge in lexical representation
Authors: József Andor
Journal: Behavioral and Brain Sciences (2003)

In this commentary I discuss the role of types of knowledge and conceptual structures in lexical representation, revealing the explanatory potential of frame-based knowledge. Although frame-based lexical semantics is not alien to the theoretical model outlined in Jackendoff's conceptual semantics, testing its relevance to the analysis of the lexical evidence presented in his book has been left out of consideration.
High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro.
Authors: Y Almaden, A Hernandez, V Torregrosa, A Canalejo, L Sabate, L Fernandez Cruz, J M Campistol, A Torres, M Rodriguez
Journal: Journal of the American Society of Nephrology (1998)

Phosphate retention plays an important role in the pathogenesis of secondary hyperparathyroidism in patients with renal failure. In in vitro studies, high extracellular phosphate levels directly stimulate PTH secretion in rat and bovine parathyroid tissue. The present study evaluates the effect of high phosphate levels on the secretion of PTH and the production of prepro PTH mRNA in human hyperplastic parathyroid glands. The study includes parathyroid glands obtained from patients with primary adenomas and from hemodialysis and kidney-transplant patients with diffuse and nodular secondary hyperplasia. The experiments were performed in vitro using small pieces of parathyroid tissue. The ability of high calcium levels to decrease PTH secretion was less in adenomas than in secondary hyperplasia; among the secondary hyperplasia, nodular was less responsive to an increase in calcium than diffuse hyperplasia. In diffuse hyperplasia, PTH secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA levels increased after incubation in 4 mM phosphate. Similar results were obtained with nodular hyperplasia, except that the elevation of PTH secretion in response to 3 mM phosphate did not attain statistical significance. In adenomas, high calcium concentrations (1.5 mM) did not result in inhibition of PTH secretion, independent of the phosphate concentration, and the prepro PTH mRNA was not significantly increased by high phosphate levels. In conclusion, first, the PTH secretory response to an increase in calcium concentration is less in nodular than diffuse hyperplasia; second, high phosphate levels directly affect PTH secretion and gene expression in patients with advanced secondary hyperparathyroidism.
Comparative effectiveness and tolerance of treatments for<i>Helicobacter pylori</i>: systematic review and network meta-analysis
Authors: Bao-Zhu Li, Diane Erin Threapleton, Ji-Yao Wang, Jian-Ming Xu, Jin-Qiu Yuan, Chao Zhang, Peng Li, Qian-Ling Ye, Biao Guo, Chen Mao, Dong-Qing Ye
Journal: BMJ (2015)

<b>Objective</b> To determine the most efficacious treatment for eradication of <i>Helicobacter pylori</i> with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens. <b>Design</b> Systematic review and network meta-analysis. <b>Data sources</b> Cochrane Library, PubMed, and Embase without language or date restrictions. <b>Study selection</b> Full text reports of randomised controlled trials that compared different eradication treatments for <i>H pylori</i> among adults. <b>Results</b> Of the 15 565 studies identified, 143 were eligible and included. Data on 14 kinds of treatments were available. Of 91 possible comparisons for the efficacy outcome, 34 were compared directly and the following treatments performed better: seven days of concomitant treatment (proton pump inhibitor and three kinds of antibiotics administered together), 10 or 14 days of concomitant treatment, 10 or 14 days of probiotic supplemented triple treatment (standard triple treatment which is probiotic supplemented), 10 or 14 days of levofloxacin based triple treatment (proton pump inhibitor, levofloxacin, and antibiotic administered together), 14 days of hybrid treatment (proton pump inhibitor and amoxicillin used for seven days, followed by a proton pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another seven days), and 10 or 14 days of sequential treatment (five or seven days of a proton pump inhibitor plus amoxicillin, followed by five or seven additional days of a proton pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin). In terms of tolerance, all treatments were considered tolerable, but seven days of probiotic supplemented triple treatment and seven days of levofloxacin based triple treatment ranked best in terms of the proportion of adverse events reported. <b>Conclusion</b> Comparison of different eradication treatments for <i>H pylori</i> showed that concomitant treatments, 10 or 14 days of probiotic supplemented triple treatment, 10 or 14 days of levofloxacin based triple treatment, 14 days of hybrid treatment, and 10 or 14 days of sequential treatment might be better alternatives for the eradication of <i>H pylori</i>.
Why do patients not keep their appointments? Prospective study in a gastroenterology outpatient clinic
Authors: A Murdock, C Rodgers, H Lindsay, T C K Tham
Journal: Journal of the Royal Society of Medicine (2002)

Unkept outpatient appointments are a drain on resources. In a prospective study we asked non-attenders at a gastroenterology clinic why they had missed their appointment. 103 patients missed their appointment (14% of the total invited); 3 had died. The remaining 100 were asked to complete questionnaires, 68 by mail (43 returned) and 32 by telephone (30 successful); the response rate was thus 73%. 49 of the respondents were new patients, 6 of them with urgent referrals. The explanations for non-attendance by the 73 patients were: forgot to attend or to cancel (30%); no reason (26%); clerical errors (10%); felt better (8%), fearful of being seen by junior doctor (3%); inpatient in another hospital (3%); miscellaneous other (20%). 13 (27%) of the review patients had not kept one or more previous appointments. The non-attendance rates for different clinics ranged from 10% to 25% (average 14%). A substantial number of non-attenders claimed to have forgotten their appointment or to cancel it. If, as we surmise, this reflects apathy, no strategy to improve attendance is likely to have great impact. Since the non-attendance rate is reasonably constant, it can be taken into account when patients are booked.
Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph)
Authors: M. Kamper-Jørgensen, K. Rostgaard, S.L. Glaser, S.H. Zahm, W. Cozen, K.E. Smedby, S. Sanjosé, E.T. Chang, T. Zheng, C. La Vecchia, D. Serraino, A. Monnereau, E.V. Kane, L. Miligi, P. Vineis, J.J. Spinelli, J.R. McLaughlin, P. Pahwa, J.A. Dosman, M. Vornanen, L. Foretova, M. Maynadie, N. Becker, A. Nieters, P. Brennan, P. Boffetta, P. Cocco, H. Hjalgrim, A. Staines
Journal: Annals of Oncology (2013)
Roles for the Stem Cell–Associated Intermediate Filament Nestin in Prostate Cancer Migration and Metastasis
Authors: Wolfram Kleeberger, G. Steven Bova, Matthew E. Nielsen, Mehsati Herawi, Ai-Ying Chuang, Jonathan I. Epstein, David M. Berman
Journal: Cancer Research (2007)

Abstract The intermediate filament protein Nestin identifies stem/progenitor cells in adult tissues, but the function of Nestin is poorly understood. We investigated Nestin expression and function in common lethal cancers. Nestin mRNA was detected in cell lines from small cell lung, and breast cancers, and particularly elevated in cell lines derived from prostate cancer metastases. Whereas the androgen-independent lines PC3, 22RV1, and DU145 all expressed Nestin transcripts under standard culture conditions, the androgen-dependent line LnCaP expressed Nestin only on androgen withdrawal. We confirmed associations of Nestin expression, androgen withdrawal, and metastatic potential by immunohistochemical analysis of samples from 254 prostate cancer patients. Cytoplasmic Nestin protein was readily identifiable in prostate cancer cells from 75% of patients with lethal androgen-independent disease, even in cancer sampled from the prostate itself. However, Nestin expression was undetectable in localized androgen-deprived tumors and in metastases without prior androgen deprivation. To address its function, we reduced Nestin levels with short hairpin RNAs, markedly inhibiting in vitro migration and invasion in prostate cancer cells but leaving cell growth intact. Nestin knockdown also diminished metastases 5-fold compared with controls despite uncompromised tumorigenicity at the site of inoculation. These results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis. Activity of this pathway may be selected by the extraprostatic environment or, as supported by our data, may originate within the prostate after androgen deprivation. Further dissection of this novel Nestin migration pathway may lead to strategies to prevent and neutralize metastatic spread. [Cancer Res 2007;67(19):9199–206]