tbuckley/cabot-search huggingface dataset:
Determinants of cough in young adults participating in the European Community Respiratory Health Survey
Authors: C. Janson, S. Chinn, D. Jarvis, P. Burney
Journal: European Respiratory Journal (2001)

Cough is a common symptom that affects a large proportion of the general population. The aim of this investigation was to identify determinants of nocturnal, nonproductive and productive cough in population samples from different countries. In a cross-sectional international population survey, 18,277 subjects (20–48 yrs) from 16 countries answered an interview-led questionnaire. Total and specific immunoglobulin-;E was measured and spirometry was performed. Three types of cough were defined: nocturnal, nonproductive and productive cough. The relation of the independent variables to cough was estimated by means of logistic regression for each centre or country and combined across centre or country by random-effects meta-analysis. The median prevalence of nocturnal, nonproductive and productive cough in the different centres was 30.7%, 10.2% and 10.2%, respectively. Nocturnal and nonproductive cough were related to female sex (adjusted odds ratio (OR)=2.08 and 1.27, respectively), while nocturnal and productive cough were related to rhinitis (OR=1.46 and 1.61, respectively). All three types of cough were related to asthma, tobacco smoking, environmental tobacco smoke and obesity. Females are more likely to report nocturnal and nonproductive cough than males. Cough was related to treatable disorders, like asthma and rhinitis, as well as avoidable factors, such as tobacco smoking and environmental tobacco smoke.
APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema
Authors: Kristin M. Burkart, Ani Manichaikul, Jemma B. Wilk, Firas S. Ahmed, Gregory L. Burke, Paul Enright, Nadia N. Hansel, Demondes Haynes, Susan R. Heckbert, Eric A. Hoffman, Joel D. Kaufman, Jun Kurai, Laura Loehr, Stephanie J. London, Yang Meng, George T. O’Connor, Elizabeth Oelsner, Marcy Petrini, Tess D. Pottinger, Charles A. Powell, Susan Redline, Jerome I. Rotter, Lewis J. Smith, María Soler Artigas, Martin D. Tobin, Michael Y. Tsai, Karol Watson, Wendy White, Taylor R. Young, Stephen S. Rich, R. Graham Barr
Journal: European Respiratory Journal (2013)

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.
Scopolamine improves autonomic balance in advanced congestive heart failure.
Authors: M T La Rovere, A Mortara, P Pantaleo, R Maestri, F Cobelli, L Tavazzi
Journal: Circulation (1994)

Sympathetic hyperactivity and parasympathetic withdrawal in patients with congestive heart failure correlate closely with disease severity and overall survival. The modulating effects of drugs on the autonomic dysfunction may contribute to improve survival. Low-dose scopolamine has a vagomimetic effect in normal subjects and patients after acute myocardial infarction. We assessed whether transdermal scopolamine would increase vagal activity in patients with congestive heart failure.Heart rate variability was assessed at baseline, 24 hours after one patch of transdermal scopolamine, and 48 hours after scopolamine withdrawal in 21 patients with moderate to severe heart failure. Scopolamine increased both time- and frequency-domain parameters of heart rate variability. Specifically, the mean RR interval and its SD increased by 5.5% (P < .001) and 45% (P < .001), respectively. The change remained significant when corrected for mean heart rate with a 39% (P < .01) increase of the coefficient of variation. The absolute power of the high-frequency component was also significantly augmented. All the parameters returned to baseline after scopolamine withdrawal. Individual analysis showed that in the 7 patients in whom scopolamine did not increase mean RR interval, heart rate variability did not change.Transdermal scopolamine increases vagal activity as assessed by heart rate variability in patients with congestive heart failure. This autonomic modulation does not occur in all patients and can be predicted by RR interval changes. Whether such restoration of the autonomic balance might have beneficial effects in the long-term management of patients with congestive heart failure remains to be determined.
MAST CELL COULD REGULATE THE SURVIVAL OF CARDIOMYOCYTES IN A MYOCARDIAL INFARCTION RAT MODEL
Authors: Youngkeun Ahn, Jin Sook Kwon, Yong Sook Kim, Ae Sin Cho, Mun Hwa Hong, Myung Ho Jeong, Seung Uk Lee, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang
Journal: Journal of the American College of Cardiology (2010)
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade
Authors: Simon J. Dovedi, Amy L. Adlard, Grazyna Lipowska-Bhalla, Conor McKenna, Sherrie Jones, Eleanor J. Cheadle, Ian J. Stratford, Edmund Poon, Michelle Morrow, Ross Stewart, Hazel Jones, Robert W. Wilkinson, Jamie Honeychurch, Tim M. Illidge
Journal: Cancer Research (2014)

Abstract Radiotherapy is a major part in the treatment of most common cancers, but many patients experience local recurrence with metastatic disease. In evaluating response biomarkers, we found that low doses of fractionated radiotherapy led to PD-L1 upregulation on tumor cells in a variety of syngeneic mouse models of cancer. Notably, fractionated radiotherapy delivered in combination with αPD-1 or αPD-L1 mAbs generated efficacious CD8+ T-cell responses that improved local tumor control, long-term survival, and protection against tumor rechallenge. These favorable outcomes were associated with induction of a tumor antigen–specific memory immune response. Mechanistic investigations showed that IFNγ produced by CD8+ T cells was responsible for mediating PD-L1 upregulation on tumor cells after delivery of fractionated radiotherapy. Scheduling of anti–PD-L1 mAb was important for therapeutic outcome, with concomitant but not sequential administration with fractionated radiotherapy required to improve survival. Taken together, our results reveal the mechanistic basis for an adaptive response by tumor cells that mediates resistance to fractionated radiotherapy and its treatment failure. With attention to scheduling, combination immunoradiotherapy with radiotherapy and PD-1/PD-L1 signaling blockade may offer an immediate strategy for clinical evaluation to improve treatment outcomes. Cancer Res; 74(19); 5458–68. ©2014 AACR.
Rewiring of Posttranscriptional RNA Regulons: Puf4p in Fungi as an Example
Authors: Huifeng Jiang, Xiaoxian Guo, Lin Xu, Zhenglong Gu
Journal: Molecular Biology and Evolution (2012)

It has been increasingly clear that changes in gene regulation play important roles in physiological and phenotypic evolution. Rewiring gene-regulatory networks, i.e., alteration of the gene-regulation system for different biological functions, has been demonstrated in various species. Posttranscriptional regulons have prominent roles in coordinating gene expression in a variety of eukaryotes. In this study, using Puf4p in fungi as an example, we demonstrate that posttranscriptional regulatory networks can also be rewired during evolution. Although Puf4p is highly conserved in fungi, targets of the posttranscriptional regulon are functionally diverse among known fungal species. In the Saccharomycotina subdivision, target genes of Puf4p mostly conduct function in the nucleolus; however, in the Pezizomycotina subdivision, they are enriched in the mitochondria. Furthermore, we demonstrate different regulation efficiencies of mitochondrial function by PUF proteins in different fungal clades. Our results indicate that rewiring of posttranscription regulatory networks may be an important way of generating genetic novelties in gene regulation during evolution.
PAR<sub>2</sub>expression in peripheral blood monocytes of patients with rheumatoid arthritis
Authors: A Crilly, E Burns, M B Nickdel, J C Lockhart, M E Perry, P W Ferrell, D Baxter, J Dale, L Dunning, H Wilson, J S Nijjar, J A Gracie, W R Ferrell, I B McInnes
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> Proteinase-activated receptor 2 (PAR<sub>2</sub>) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functio©nal significance of PAR<sub>2</sub> expression on rheumatoid arthritis (RA)-derived leucocyte subsets. <h3>Methods</h3> Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR<sub>2</sub> on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA. <h3>Results</h3> Patients with RA had elevated but variable surface expression of PAR<sub>2</sub> on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86–4.10%) vs 0.06% (0.03–0.81%), p&lt;0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR<sub>2</sub> expression in patients with RA compared with controls (3.05% (0.36–11.82%) vs 0.08% (0.02–0.28%), p&lt;0.0001). For both subsets, PAR<sub>2</sub> expression was significantly higher (p&lt;0.00001) in patients with high levels of disease activity: PAR<sub>2</sub> expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR<sub>2</sub> expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p&lt;0.05). PAR<sub>2</sub> expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR<sub>2</sub> agonist was significantly greater in patients with RA than in patients with OA and control subjects (p&lt;0.05). <h3>Conclusions</h3> These findings are consistent with a pathogenic role for PAR<sub>2</sub> in RA.
Evaluation of the Nd/YAG laser for treatment of amateur and professional tattoos
Authors: J.E. FERGUSON, P.J. AUGUST
Journal: British Journal of Dermatology (1996)

Two hundred and twenty-one amateur tattoos and 27 professional tattoos were treated with a Nd/YAG laser (lambda 1064 nm and 532 nm). The response was expressed as the percentage area cleared of tattoo. Seventy-nine per cent of amateur black tattoos were > or = 75% clear after one to five treatments (mean 2) at 1064 nm. The response of professional tattoos was slower and less complete. Seventy-four per cent of black professional tattoos were > or = 75% clear after one to 11 treatments (mean 6.3) at 1064 nm. Red tattoos responded well to 532 nm and were > or = 75% clear after one to five treatments. Yellow, orange, blue and green tattoos were resistant to treatment. Side-effects included minor scarring in 1.2% of tattoos and transient pigmentary changes in 77% of patients.
Trends in Mortality on Peritoneal Dialysis
Authors: DOUGLAS E. SCHAUBEL, STANLEY S. A. FENTON
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Several technical and nontechnical improvements in peritoneal dialysis (PD) have occurred during recent years. Since few previous studies have examined trends in PD mortality over time, and to determine whether enhancements in PD have translated into improved patient outcomes, mortality rates among the 17,900 patients receiving PD in Canada during the period 1981-1997 were analyzed. Mortality rate ratios (RR) were estimated using Poisson regression, adjusting for age, race, gender, primary renal diagnosis, follow-up time, and type of PD (continuous ambulatory/cyclic versus intermittent). Adjusted mortality rates decreased significantly by calender period, the reduction being monotonic: RR = 0.81, 95% confidence interval [CI], 0.75 to 0.87 for 1986-1989; RR = 0.73, 95% CI, 0.67 to 0.78 for 1990-1993; RR = 0.63, 95% CI, 0.58 to 0.67 for 1994-1997, with 1981-1985 serving as the reference period (RR = 1, fixed). The improvement in mortality was fairly consistent across patient subpopulations. When analyzed separately by follow-up time window, the mortality decrease was strongest in the first 12 mo after renal replacement therapy initiation. Supplementary analysis revealed that the trend in mortality rates was not attributable to corresponding trends in transplantation or technique failure rates, or modality switching patterns. Results were quite similar whether based on an “as-treated” or “intent-to-treat” analysis. More extensive data on practice patterns would empower future studies to elucidate the cause/effect relationship between PD practice patterns and patient survival.
Lung cancer risk in subjects exposed to organic dust: an unexpected and surprising story
Authors: G Mastrangelo, R Rylander, L Cegolon, JH Lange
Journal: Thorax (2012)

In a recently published multicentre case–control study evaluating lung cancer risk among subjects exposed to organic dusts,1 the authors could not confirm the findings from previous reports in which a decreased risk was found among workers in the cotton industry and animal farmers.2

Regarding a decreased risk of lung cancer among cotton workers3–7 the authors quite rightly concluded that their material was not suitable to evaluate this relationship as their subgroups did not reflect the critical exposure groups, i.e. those exposed to high levels of endotoxin such as cardroom workers and weavers.8 

For farmers we believe that the multicentre case–control study findings have the same shortcomings …
Early and late complications associated with transcatheter occlusion of secundum atrial septal defect
Authors: Massimo Chessa, Mario Carminati, Gianfranco Butera, Roberta Margherita Bini, Manuela Drago, Luca Rosti, Alessandro Giamberti, Giuseppe Pomè, Eduardo Bossone, Alessandro Frigiola
Journal: Journal of the American College of Cardiology (2002)
Fetuin-A, Type 2 Diabetes, and Risk of Cardiovascular Disease in Older Adults
Authors: Majken K. Jensen, Traci M. Bartz, Kenneth J. Mukamal, Luc Djoussé, Jorge R. Kizer, Russell P. Tracy, Susan J. Zieman, Eric B. Rimm, David S. Siscovick, Michael Shlipak, Joachim H. Ix
Journal: Diabetes Care (2012)

OBJECTIVE Fetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes. RESEARCH DESIGN AND METHODS This was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008. RESULTS Mean age was 75 years, and 61% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95% CI, 0.88–0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93–1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85–0.97) and 0.87 (0.79–0.95), respectively]. CONCLUSIONS The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes.
Impact of Specific Glucose-Control Strategies on Microvascular and Macrovascular Outcomes in 58,000 Adults With Type 2 Diabetes
Authors: Romain Neugebauer, Bruce Fireman, Jason A. Roy, Patrick J. O’Connor
Journal: Diabetes Care (2013)

OBJECTIVE Comparative effectiveness research methods are used to compare the effect of four distinct glucose-control strategies on subsequent myocardial infarction and nephropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 58,000 adults with type 2 diabetes and A1C &amp;lt;7% (53 mmol/mol) while taking two or more oral agents or basal insulin had subsequent A1C ≥7% (53 mmol/mol) to 8.5% (69 mmol/mol). Follow-up started on date of first A1C ≥7% and ended on date of a specific clinical event, death, disenrollment, or study end. Glucose-control strategies were defined as first intensification of glucose-lowering therapy at A1C ≥7, ≥7.5, ≥8, or ≥8.5% with subsequent control for treatment adherence. Logistic marginal structural models were fitted to assess the discrete-time hazards for each dynamic glucose-control strategy, adjusting for baseline and time-dependent confounding and selection bias through inverse probability weighting. RESULTS After adjustment for age, sex, race/ethnicity, comorbidities, blood pressure, lipids, BMI, and other covariates, progressively more aggressive glucose-control strategies were associated with reduced onset or progression of albuminuria but not associated with significant reduction in occurrence of myocardial infarction or preserved renal function based on estimated glomerular filtration rate over 4 years of follow-up. CONCLUSIONS In a large representative cohort of adults with type 2 diabetes, more aggressive glucose-control strategies have mixed short-term effects on microvascular complications and do not reduce the myocardial infarction rate over 4 years of follow-up. These findings are consistent with the results of recent clinical trials, but confirmation over longer periods of observation is needed.
Immediate Sterility after Vasectomy
Authors: D. U. Hay
Journal: BMJ (1973)

A 2·5-ml injection of 1/1,000 solution of euflavine given down each vas during vasectomy for sterilization will destroy all sperms within the semen and eliminate the necessity for examining two consecutive specimens of semen for azoospermia after the operation. No local inflammatory response has been observed in the seminal vesicles or prostate of 81 consecutive patients in whom the method has been used.
Safety of Computed Tomography in Patients With Cardiac Rhythm Management Devices
Authors: Ayman A. Hussein, Ameer Abutaleb, Jean Jeudy, Timothy Phelan, Ronak Patel, Melsjan Shkullaku, Faisal Siddiqi, Vincent See, Anastasios Saliaris, Stephen R. Shorofsky, Timm Dickfeld
Journal: Journal of the American College of Cardiology (2014)
Clinical and atopic parameters and airway inflammatory markers in childhood asthma: a factor analysis
Authors: T F Leung
Journal: Thorax (2005)

Recent studies have repeatedly shown weak correlations among lung function parameters, atopy, exhaled nitric oxide level (Feno), and airway inflammatory markers, suggesting that they are non-overlapping characteristics of asthma in adults. A study was undertaken to determine, using factor analysis, whether the above features represent separate dimensions of childhood asthma.Clinically stable asthmatic patients aged 7-18 years underwent spirometric testing, methacholine bronchial challenge, blood sampling for atopy markers and chemokine levels (macrophage derived chemokine (MDC), thymus and activation regulated chemokine (TARC), and eotaxin), Feno, and chemokines (MDC and eotaxin) and leukotriene B(4) measurements in exhaled breath condensate (EBC).The mean (SD) forced expiratory volume in 1 second (FEV1) and Feno of 92 patients were 92.1 (15.9)% predicted and 87.3 (65.7) ppb, respectively. 59% of patients received inhaled corticosteroids. Factor analysis selected four different factors, explaining 55.5% of total variance. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.587. Plasma total and specific IgE levels, peripheral blood eosinophil percentage, and Feno loaded on factor 1; plasma TARC and MDC concentrations on factor 2; MDC, eotaxin and leukotriene B4 concentrations in EBC on factor 3; and plasma eotaxin concentration together with clinical indices including body mass index and disease severity score loaded on factor 4. Post hoc factor analyses revealed similar results when outliers were excluded.The results suggest that atopy related indices and airway inflammation are separate dimensions in the assessment of childhood asthma, and inflammatory markers in peripheral blood and EBC are non-overlapping factors of asthma.
Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment
Authors: Edward K. Chow, Xue-Qing Zhang, Mark Chen, Robert Lam, Erik Robinson, Houjin Huang, Daniel Schaffer, Eiji Osawa, Andrei Goga, Dean Ho
Journal: Science Translational Medicine (2011)

Enhancing chemotherapeutic efficiency through improved drug delivery would facilitate treatment of chemoresistant cancers, such as recurrent mammary tumors and liver cancer. One way to improve drug delivery is through the use of nanodiamond (ND) therapies, which are both scalable and biocompatible. Here, we examined the efficacy of an ND-conjugated chemotherapeutic in mouse models of liver and mammary cancer. A complex (NDX) of ND and doxorubicin (Dox) overcame drug efflux and significantly increased apoptosis and tumor growth inhibition beyond conventional Dox treatment in both murine liver tumor and mammary carcinoma models. Unmodified Dox treatment represents the clinical standard for most cancer treatment regimens, and NDX had significantly decreased toxicity in vivo compared to standard Dox treatment. Thus, ND-conjugated chemotherapy represents a promising, biocompatible strategy for overcoming chemoresistance and enhancing chemotherapy efficacy and safety.