tbuckley/cabot-search huggingface dataset:
The epidemiological impasse
Authors: P.H. Quanjer, P.L. Enright, M.R. Miller
Journal: European Respiratory Journal (2011)

The epidemiological impasseTo the Editors:We read with interest the letter of QUANJER et al. [1] persuading the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee to abandon the fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ,0.70 in favour of the lower limit of normal (LLN).We feel that, in the current debate, some basic epidemiological principles have been overlooked.We will briefly address these principles in an attempt to clear up the discussion. QUANJER et al.[1] point out that numerous studies have reported a higher prevalence of chronic obstructive pulmonary disease (COPD) when using the fixed FEV1/FVC ,0.70 criterion when compared with the LLN.They interpret this as an ''overdiagnosis'' of COPD [2].However, this neither implies nor ascertains that the LLN is the superior diagnostic.Conversely, one can state that the LLN leads to ''underdiagnosis'' of COPD.As long as either the fixed criterion or the LLN are not compared with a gold standard of COPD (when possible, a test with specificity and sensitivity approaching 100%), one should realise that it is impossible to label either criterion as superior.The only valid conclusion of comparative studies lacking that gold standard is that both criteria differ.How then to solve the issue?COPD is and remains a clinical diagnosis and therefore a panel decision on its absence or presence by taking into account all relevant clinical factors, such as age, respiratory complaints, smoking history, etc., is the classical approach.The fixed FEV1/FVC ,0.70 criterion and the LLN should subsequently be compared with that panel diagnosis of COPD and the sensitivity/specificity evaluated.Unfortunately, we are unaware of any such studies and, in the mean time, any discussion and debate about the superiority/inferiority of a particular spirometric threshold will remain unproductive.In conclusion, with the currently available literature it is impossible to label either threshold as superior or suitable.
miR-27b controls venous specification and tip cell fate
Authors: Dauren Biyashev, Dorina Veliceasa, Jacek Topczewski, Jolanta M. Topczewska, Igor Mizgirev, Elena Vinokour, Alagarsamy L. Reddi, Jonathan D. Licht, Sergei Y. Revskoy, Olga V. Volpert
Journal: Blood (2011)
Clinical and Biologic Features Predictive of Survival After Relapse of Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project
Authors: Wendy B. London, Victoria Castel, Tom Monclair, Peter F. Ambros, Andrew D.J. Pearson, Susan L. Cohn, Frank Berthold, Akira Nakagawara, Ruth L. Ladenstein, Tomoko Iehara, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2011)

Purpose Survival after neuroblastoma relapse is poor. Understanding the relationship between clinical and biologic features and outcome after relapse may help in selection of optimal therapy. Our aim was to determine which factors were significantly predictive of postrelapse overall survival (OS) in patients with recurrent neuroblastoma—particularly whether time from diagnosis to first relapse (TTFR) was a significant predictor of OS. Patients and Methods Patients with first relapse/progression were identified in the International Neuroblastoma Risk Group (INRG) database. Time from study enrollment until first event and OS time starting from first event were calculated. Cox regression models were used to calculate the hazard ratio of increased death risk and perform survival tree regression. TTFR was tested in a multivariable Cox model with other factors. Results In the INRG database (N = 8,800), 2,266 patients experienced first progression/relapse. Median time to relapse was 13.2 months (range, 1 day to 11.4 years). Five-year OS from time of first event was 20% (SE, ± 1%). TTFR was statistically significantly associated with OS time in a nonlinear relationship; patients with TTFR of 36 months or longer had the lowest risk of death, followed by patients who relapsed in the period of 0 to less than 6 months or 18 to 36 months. Patients who relapsed between 6 and 18 months after diagnosis had the highest risk of death. TTFR, age, International Neuroblastoma Staging System stage, and MYCN copy number status were independently predictive of postrelapse OS in multivariable analysis. Conclusion Age, stage, MYCN status, and TTFR are significant prognostic factors for postrelapse survival and may help in the design of clinical trials evaluating novel agents.
BRAIN BIOCHEMISTRY IN SCHIZOPHRENIA
Authors: Raymond Levy, E.D. Bird, E.G. Spokes, Joanna Barnes, A.V.P. Mackay, L.L. Iversen, Michael Shepherd, ElaineK. Perry, Garry Blessed, RobertH. Perry, BernardE. Tomlinson, T.J. Crow, F. Owen, A.J. Cross, R. Lofthouse, A. Longden
Journal: The Lancet (1978)
Particle size matters: diagnostics and treatment of small airways involvement in asthma
Authors: J. Cohen, D.S. Postma, W.R. Douma, J.M. Vonk, A.H. De Boer, N.H.T. ten Hacken
Journal: European Respiratory Journal (2010)

Small airways are an important site of inflammation and obstruction in asthma, which contributes to the severity of airway hyperresponsiveness (AHR) that is usually measured by nebulisation of large-particle stimuli. We investigated whether small and large particle sizes of aerosolised adenosine monophospate (AMP) provoke similar severity of AHR. Additionally, effects of the small-particle inhaled corticosteroid (ICS) ciclesonide and large-particle ICS fluticasone on AHR to large- and small-particle size AMP were assessed. After a 4-week run-in period using open-label fluticasone (100 μg b.i.d .), 37 mild-to-moderate asthmatics underwent provocations with standard-size (3.7 μm), large-particle (9.9 μm) and small-particle (1.06 μm) AMP. Subjects received 4-week ciclesonide (160 μg s.i.d. ) or fluticasone (100 μg b.i.d .) treatment (double-blind and double-dummy) followed by large- and small-particle AMP provocation. Small-particle AMP induced a 20% decrease in forced expiratory volume in 1 s (FEV 1 ) at a significantly higher dose than large-particle AMP. Ciclesonide and fluticasone had comparable effects on AMP provocations. Not all subjects reached the provocative concentration causing a 20% fall in FEV 1 (PC 20 ) at the highest AMP dose. In those who did, ciclesonide improved small-particle AMP PC 20 by 1.74 doubling doses (DD) (p = 0.03), whereas fluticasone did not . Conversely , fluticasone improved large-particle AMP PC 20 significantly (1.32 DD; p = 0.03), whereas ciclesonide did not. Small-particle AMP provocation appears to be a promising tool to assess changes in small airway inflammation. Future adjustments are necessary taking into account the very small particle size used, with large exhaled fractions. In asthmatics reaching a PC 20 with small- and large-particle AMP provocations, ciclesonide improves hyperresponsiveness to small particle size AMP, and fluticasone to large particle size. This warrants further research to target provocations and treatment to specific airway sizes.
AC1MMYR2, an Inhibitor of Dicer-Mediated Biogenesis of Oncomir miR-21, Reverses Epithelial–Mesenchymal Transition and Suppresses Tumor Growth and Progression
Authors: Zhendong Shi, Junxia Zhang, Xiaomin Qian, Lei Han, Kailiang Zhang, Luyue Chen, Jilong Liu, Yu Ren, Ming Yang, Anling Zhang, Peiyu Pu, Chunsheng Kang
Journal: Cancer Research (2013)

The extensive involvement of miRNAs in cancer pathobiology has opened avenues for drug development based on oncomir inhibition. Dicer is the core enzyme in miRNA processing that cleaves the terminal loop of precursor microRNAs (pre-miRNAs) to generate mature miRNA duplexes. Using the three-dimensional structure of the Dicer binding site on the pre-miR-21 oncomir, we conducted an in silico high-throughput screen for small molecules that block miR-21 maturation. By this method, we identified a specific small-molecule inhibitor of miR-21, termed AC1MMYR2, which blocked the ability of Dicer to process pre-miR-21 to mature miR-21. AC1MMYR2 upregulated expression of PTEN, PDCD4, and RECK and reversed epithelial-mesenchymal transition via the induction of E-cadherin expression and the downregulation of mesenchymal markers, thereby suppressing proliferation, survival, and invasion in glioblastoma, breast cancer, and gastric cancer cells. As a single agent in vivo, AC1MMYR2 repressed tumor growth, invasiveness, and metastasis, increasing overall host survival with no observable tissue cytotoxicity in orthotopic models. Our results offer a novel, high-throughput method to screen for small-molecule inhibitors of miRNA maturation, presenting AC1MMYR2 as a broadly useful candidate antitumor drug.
Insulin resistance and non-insulin-dependent diabetes
Authors: J. N. de Neeling
Journal: JAMA (1995)

To the Editor.  —Dr Pimenta and colleagues 1 state that they tested the hypothesis that insulin resistance precedes impaired beta-cell function in people genetically predisposed to develop non—insulin-dependent diabetes mellitus (NIDDM), but their study could not address their primary hypothesis.  First, Pimenta et al took care to match the control subjects to the subjects with a first-degree NIDDM relative for body mass index. But rather than body mass index simply being the environmental factor,1 it seems plausible that there is some genetic constitution that, in the presence of excess energy intake or diminished physical activity, manifests itself phenotypically as hyperinsulinemia and obesity. 2,3 Thus, matching for obesity implies also matching, at least partially, for the insulin-resistant genotype, which clearly undermines the validity of the comparison between index and control groups with respect to the degree of genetically determined insulin sensitivity. Second, from the data on the age of the study
A Family of Drug Transporters: the Multidrug Resistance-Associated Proteins
Authors: P. Borst, R. Evers, M. Kool, J. Wijnholds
Journal: JNCI Journal of the National Cancer Institute (2000)

The human multidrug resistance-associated protein (MRP) family currently has seven members. The ability of several of these membrane proteins to transport a wide range of anticancer drugs out of cells and their presence in many tumors make them prime suspects in unexplained cases of drug resistance, although proof that they contribute to clinical drug resistance is still lacking. Recent studies have begun to clarify the function of the MRP family members. MRPs are organic anion transporters; i.e., they transport anionic drugs, exemplified by methotrexate, and neutral drugs conjugated to acidic ligands, such as glutathione (GSH), glucuronate, or sulfate. However, MRP1, MRP2, and MRP3 can also cause resistance to neutral organic drugs that are not known to be conjugated to acidic ligands by transporting these drugs together with free GSH. MRP1 can even confer resistance to arsenite and MRP2 to cisplatin, again probably by transporting these compounds in complexes with GSH. MRP4 overexpression is associated with high-level resistance to the nucleoside analogues 9-(2-phosphonylmethoxyethyl) adenine and azidothymidine, both of which are used as anti-human immunodeficiency virus drugs. MRPs may, therefore, also have a role in resistance against nucleoside analogues used in cancer chemotherapy. Mice without Mrp1, a high-affinity leukotriene C4 transporter, have an altered response to inflammatory stimuli but are otherwise healthy and fertile. MRP2 is the major transporter responsible for the secretion of bilirubin glucuronides into bile, and humans without MRP2 develop a mild liver disease known as the Dubin–Johnson syndrome. The physiologic functions of the other MRPs are not known. Whether long-term inhibition of MRPs in humans can be tolerated (assuming that suitable inhibitors will be found) remains to be determined.
Down Regulation of High in Normal-1 (<b> <i>HIN-1</i> </b>) is a Frequent Event in Stage I Non-Small Cell Lung Cancer and Correlates with Poor Clinical Outcome
Authors: Antonio Marchetti, Fabio Barassi, Carla Martella, Antonio Chella, Simona Salvatore, Antonio Castrataro, Felice Mucilli, Rocco Sacco, Fiamma Buttitta
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of this study was to evaluate the prevalence and the clinical significance of HIN-1 mRNA expression in early stage non-small cell lung carcinomas (NSCLCs). Experimental Design: A series of 91 NSCLC patients with stage I neoplastic disease was studied. HIN-1 expression was investigated by quantitative real-time reverse transcription-PCR on tumor specimens and matching normal lung tissues. Variables were analyzed by χ2 test and Fisher’s exact tests. Survival was evaluated with the method of Kaplan-Meier. Multivariate analysis was performed with Cox’s proportional hazards model. Results: Seventy one (78%) tumors showed a reduction of HIN-1 mRNA compared with the normal counterpart. The range of reduction varied greatly, from −2-fold to −3350-fold. Setting a cutoff at −46-fold (median value of HIN-1 mRNA reduction), 46 cases (51%) had a markedly reduced expression, and 45 cases (49%) showed a normal or slightly reduced expression. A statistically significant association between low HIN-1 mRNA levels and T status was observed (P = 0.036). Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between HIN-1 expression and both overall survival (P = 0.0095) and disease-free survival (P = 0.0122). A multivariate analysis, performed by Cox’s proportional hazards regression model, confirmed that a low HIN-1 expression was the only significant factor to predict poor prognosis. Conclusions: Our data indicate that HIN-1 expression, measured by real-time reverse transcription-PCR, is a possible prognostic factor in patients with stage I NSCLC. Additional studies are required to further validate this potential prognostic marker.
The International Collaboration on Air Pollution and Pregnancy Outcomes: Initial Results
Authors: Jennifer D. Parker, David Q. Rich, Svetlana V. Glinianaia, Jong Han Leem, Daniel Wartenberg, Michelle L. Bell, Matteo Bonzini, Michael Brauer, Lyndsey Darrow, Ulrike Gehring, Nelson Gouveia, Paolo Grillo, Eunhee Ha, Edith H. van den Hooven, Bin Jalaludin, Bill M. Jesdale, Johanna Lepeule, Rachel Morello-Frosch, Geoffrey G. Morgan, Rémy Slama, Frank H. Pierik, Angela Cecilia Pesatori, Sheela Sathyanarayana, Juhee Seo, Matthew Strickland, Lillian Tamburic, Tracey J. Woodruff
Journal: Environmental Health Perspectives (2011)

Background: The findings of prior studies of air pollution effects on adverse birth outcomes are difficult to synthesize because of differences in study design.Objectives: The International Collaboration on Air Pollution and Pregnancy Outcomes was formed to understand how differences in research methods contribute to variations in findings. We initiated a feasibility study to a) assess the ability of geographically diverse research groups to analyze their data sets using a common protocol and b) perform location-specific analyses of air pollution effects on birth weight using a standardized statistical approach.Methods: Fourteen research groups from nine countries participated. We developed a protocol to estimate odds ratios (ORs) for the association between particulate matter ≤ 10 μm in aerodynamic diameter (PM10) and low birth weight (LBW) among term births, adjusted first for socioeconomic status (SES) and second for additional location-specific variables.Results: Among locations with data for the PM10 analysis, ORs estimating the relative risk of term LBW associated with a 10-μg/m3 increase in average PM10 concentration during pregnancy, adjusted for SES, ranged from 0.63 [95% confidence interval (CI), 0.30–1.35] for the Netherlands to 1.15 (95% CI, 0.61–2.18) for Vancouver, with six research groups reporting statistically significant adverse associations. We found evidence of statistically significant heterogeneity in estimated effects among locations.Conclusions: Variability in PM10–LBW relationships among study locations remained despite use of a common statistical approach. A more detailed meta-analysis and use of more complex protocols for future analysis may uncover reasons for heterogeneity across locations. However, our findings confirm the potential for a diverse group of researchers to analyze their data in a standardized way to improve understanding of air pollution effects on birth outcomes.
Chemosensitivity and outcome of BRCA1- and BRCA2-associated ovarian cancer patients after first-line chemotherapy compared with sporadic ovarian cancer patients
Authors: P.M.L.H. Vencken, M. Kriege, D. Hoogwerf, S. Beugelink, M.E.L. van der Burg, M.J. Hooning, E.M. Berns, A. Jager, M. Collée, C.W. Burger, C. Seynaeve
Journal: Annals of Oncology (2011)
Influence of Affective States and Psychoactive Drugs on Verbal Learning and Memory
Authors: GEORGE M. HENRY, HERBERT WEINGARTNER, DENNIS L. MURPHY
Journal: American Journal of Psychiatry (1973)

The authors found evidence of impaired performance on serial and free recall verbal learning tasks during depression and mania. Treatment with L-dopa and L-tryptophan significantly improved performance on these tasks, while imipramine, lithium carbonate, and alpha-methyl-para-tyrosine treatments had no effect. These results should be taken into account when using psychotherapeutic approaches designed to teach new response patterns to patients with affective disorders.
Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 Years after Bariatric Surgery
Authors: Lars Sjöström, Anna-Karin Lindroos, Markku Peltonen, Jarl Torgerson, Claude Bouchard, Björn Carlsson, Sven Dahlgren, Bo Larsson, Kristina Narbro, Carl David Sjöström, Marianne Sullivan, Hans Wedel
Journal: New England Journal of Medicine (2004)

Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk, but whether these benefits persist over time is unknown.
Endogenous opiates and the control of breathing in normal subjects and patients with chronic airflow obstruction.
Authors: M V Tabona, N Ambrosino, P J Barnes
Journal: Thorax (1982)

To investigate the role of endorphins in central respiratory control, the effect of naloxone, a specific opiate antagonist, on resting ventilation and ventilatory control was investigated in a randomised double-blind, placebo-controlled study of normal subjects and patients with chronic airways obstruction and mild hypercapnia due to longstanding chronic bronchitis. In 13 normal subjects the ventilatory response to hypercapnia increased after an intravenous injection of naloxone (0.1 mg/kg), ventilation (VE) at a PCO2 of 8.5 kPa increasing from 55.6 +/- SEM 6.2 to 75.9 +/- 8.21 min-1 (p less than 0.001) and the delta VE/delta PCO2 slope increasing from 28.6 +/- 4.4 to 34.2 +/- 4.21 min-1 kPa-1 (p less than 0.05). There was no significant change after placebo (saline) injection. Naloxone had no effect on resting ventilation or on the ventilatory response to hypoxia in normal subjects. In all six patients naloxone significantly (p less than 0.02) increased mouth occlusion pressure (P 0.1) responses to hypercapnia. Although there was no change in resting respiratory frequency or tidal volume patients showed a significant (p less than 0.01) decrease in inspiratory timing (Ti/Ttot) and increase in mean inspiratory flow (VT/Ti) after naloxone. These results indicate that endorphins have a modulatory role in the central respiratory response to hypercapnia in both normal subjects and patients with airways obstruction. In addition, they have an inhibitory effect on the control of tidal breathing in patients with chronic bronchitis.
Efficacy and Safety of a C1 Esterase Inhibitor Concentrate for Long-Term Prophylaxis in Hereditary Angioedema: Findings from a Large International Registry
Authors: Timothy J. Craig, Jonathan M. Edelman, Henrike Feuersenger, Michael M. Frank, Mikhail Rojavin, Ralph Shapiro, Arthur B. Vegh, Walter A. Wuillemin
Journal: Journal of Allergy and Clinical Immunology (2015)
Sex ratios and hormones in HLA related rheumatic diseases.
Authors: W.H James
Journal: Annals of the Rheumatic Diseases (1991)

The major diseases associated with HLA-B27 (Reiter's disease, ankylosing spondylitis, acute anterior uveitis, and psoriatic arthritis) all occur much more commonly in men. Published evidence indicates that the antigen HLA-B27 is associated with high testosterone concentrations in men. Moreover, the antigen HLA-B44 exerts a protective effect on one of these diseases (psoriatic arthritis), and there are external grounds for supposing that HLA-B44 indexes an antiandrogenic process. These data are interpreted as support for the hypothesis (first adumbrated nearly 20 years ago) that HLA antigens index unusual hormone concentrations, which in turn are causally related to the diseases. An examination of published reports suggests that sibs of probands with ankylosing spondylitis (and perhaps Reiter's disease) contain an excess of men, and that sibs of probands with rheumatoid arthritis contain an excess of women. These data lend further support to the hypothesis.
Risk of Colon Cancer and Coffee, Tea, and Sugar-Sweetened Soft Drink Intake: Pooled Analysis of Prospective Cohort Studies
Authors: Xuehong Zhang, Demetrius Albanes, W. Lawrence Beeson, Piet A. van den Brandt, Julie E. Buring, Andrew Flood, Jo L. Freudenheim, Edward L. Giovannucci, R. Alexandra Goldbohm, Karen Jaceldo-Siegl, Eric J. Jacobs, Vittorio Krogh, Susanna C. Larsson, James R. Marshall, Marjorie L. McCullough, Anthony B. Miller, Kim Robien, Thomas E. Rohan, Arthur Schatzkin, Sabina Sieri, Donna Spiegelman, Jarmo Virtamo, Alicja Wolk, Walter C. Willett, Shumin M. Zhang, Stephanie A. Smith-Warner
Journal: JNCI Journal of the National Cancer Institute (2010)

The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved.