tbuckley/cabot-search huggingface dataset:
The effect of fibre, gut microbiota and short-chain fatty acids on the development of asthma
Authors: Alison Thorburn, Craig McKenzie, Charles Mackay
Journal: European Respiratory Journal (2013)

The incidence of many western-world diseases, including asthma, has increased in recent decades. The hygiene hypothesis has been the prevailing model to account for this increase, however epidemiology studies also support the contribution of diet. Indeed, human populations that consume adequate or high amounts of dietary fibre have a decreased incidence of inflammatory diseases. When fibre is fermented by the gut microbiota, short-chain fatty acids (SCFAs) are produced, which have anti-inflammatory effects. Therefore, fibre, the gut microbiota and SCFAs may play an important role in the development of asthma.  In this study we investigated the role of dietary fibre, the gut microbiota and SCFAs in the development of asthma. Mice were provided high fibre, no fibre, standard diets, or SCFAs in their drinking water. We then employed models of house dust mite-induced allergic airways disease (AAD) and assessed the effects on hallmark characteristics including airways hyper-responsiveness, inflammatory cells, cytokine levels, and serum IgE.  Both a high fibre diet and the SCFA acetate reduced the development of AAD in adult mice. When pregnant mice received a high fibre diet or acetate, the development of AAD in the offspring was significantly reduced. Furthermore, consumption during the in utero phase was most effective at reducing the development of AAD. In addition we show that the mechanism requires regulatory T cells, which are regulated by inhibition of histone deacetylase activity.  These results show that dietary fibre, the gut microbiota and acetate drive epigenetic changes, which regulate the development of AAD and may explain the incidence of asthma.
Pneumonia and pandemic influenza virus A (H1N1/09). Immediate and remote results
Authors: Alexey Krivonogov, Igor Leshchenko, Zinaida Bobyleva
Journal: European Respiratory Journal (2011)

Aim:  To assess the clinical presentation, treatment outcomes and long-term results for patients with community acquired pneumonia (CAP) during an Virus A (H1N1)/09 in 2009.   Methods:  The study includes 250 cases of CAP, which developed in patients with influenza A/H1N1/09 of them men 54.8%. The average age of 45.0 years. Medication consisted of oseltamivir dose to oral 75-150 mg twice daily and cephalosporins III + macrolides II or respiratory fluoro-quinolones. After the end of inpatient treatment based on changes in the lungs according to high resolution CT (HRCT) was administered N-acetylcysteine (NAC) dose to oral 600 mg twice daily (n=41) for 92.0 (95% CI 86.2-97.7) days. Assessments included clinical symptoms, comorbidity, SpO2, laboratory tests, and X-raying.   Results:  The median period of hospitalization was 15.2 days. The median SpO2 during hospitalization 87.0%, after hospital treatment 94.2%. 76.5% of patients had a 2-side lung. The fatality rate was 10.4%. SYRS was diagnosed in 49.6% of patients (fatality rate was 1.6%), severe sepsis and septic shock in 27.6% of patients (fatality rate was 34.8%). Fatality rate in patients with obesity was 30.0%, with COPD 16.3%. X-ray changes after hospitalization were 82.4% of patients, of whom 56.6% - infiltration of the lung tissue. After treatment with NAC X-ray of the variation persisted in 57% of patients, of whom 7.0% infiltration of lung tissue and 36.0% - the picture “matte”.   Conclusion:  CAP during an epidemiology outbreak of. Influenza A/H1N1/09 characterized by severe, requires intensive care and long-term observation.
Light or moderate drinking is linked to alcohol related cancers, including breast cancer
Authors: J Rehm
Journal: BMJ (2015)

Another good reason to think before you drink

Using data from two large cohort studies in the United States, Cao and colleagues1 examine the question of whether light to moderate drinking is associated with an increased risk of cancer. This question is important for a variety of reasons related to public health and alcohol policy. Cancer is one of the major causes of death globally,2 and cancer risks are frequently cited in arguments about formulating thresholds for low risk drinking guidelines.3 For instance, when Canadian guidelines were reformulated recently in 2011, in part based on the argument that consumers would not accept strict guidelines, cancer risk at low doses of alcohol use was introduced into the public health debate.4

Cao and colleagues found that in women, light to moderate drinking was associated with an increased risk of cancers with an established link to alcohol consumption—that is, cancer of the colorectum, female breast, oral cavity, pharynx, larynx, liver, and oesophagus.5 The increased risk was driven mainly by breast cancer. Similar findings emerged for light to moderate male drinkers who had ever smoked. No significant association was found in men who never smoked, or in women outside the relation with breast cancer. Also, no association was found …
The sun’s vitamin against sun allergy
Authors: F.R. De Gruijl
Journal: British Journal of Dermatology (2011)

Journal Article The sun's vitamin against sun allergy Get access F.R. De Gruijl F.R. De Gruijl Department of Dermatology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands E‐mail: f.r.de_gruijl@lumc.nl Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 1, 1 July 2011, Pages 2–3, https://doi.org/10.1111/j.1365-2133.2011.10421.x Published: 01 July 2011
Inhibition of Survivin with YM155 Induces Durable Tumor Response in Anaplastic Thyroid Cancer
Authors: Amit Mehta, Lisa Zhang, Myriem Boufraqech, Yi Liu-Chittenden, Yaqin Zhang, Dhaval Patel, Sean Davis, Avi Rosenberg, Kris Ylaya, Rachel Aufforth, Zhuyin Li, Min Shen, Electron Kebebew
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy without any effective therapy. The aim of this study is to use a high-throughput drug library screening to identify a novel therapeutic agent that targets dysregulated genes/pathways in ATC. ExperimentalDesign: We performed quantitative high-throughput screening (qHTS) in ATC cell lines using a compound library of 3,282 drugs. Dysregulated genes in ATC were analyzed using genome-wide expression analysis and immunohistochemistry in human ATC tissue samples and ATC cell lines. In vitro and in vivo studies were performed for determining drug activity, effectiveness of targeting, and the mechanism of action. Results: qHTS identified 100 active compounds in three ATC cell lines. One of the most active agents was the first-in-class survivin inhibitor YM155. Genome-wide expression analysis and immunohistochemistry showed overexpression of survivin in human ATC tissue samples, and survivin was highly expressed in all ATC cell lines tested. YM155 significantly inhibited ATC cellular proliferation. Mechanistically, YM155 inhibited survivin expression in ATC cells. Furthermore, YM155 treatment reduced claspin expression, which was associated with S-phase arrest in ATC cells. In vivo, YM155 significantly inhibited growth and metastases and prolonged survival. Conclusions: Our data show that YM155 is a promising anticancer agent for ATC and that its target, survivin, is overexpressed in ATC. Our findings support the use of YM155 in clinical trials as a therapeutic option in advanced and metastatic ATC. Clin Cancer Res; 21(18); 4123–32. ©2015 AACR.
Diagnostic thoracoscopy in suspected malignant disease of the pleura: Pleural nodularity justifies talc poudrage
Authors: Wolf Harms, Bernd Schönhofer
Journal: European Respiratory Journal (2011)

Introduction: In a patient with suspected malignant pleural effusion and negative pleural fluid cytology, medical thoracoscopy is the next diagnostic step. Confirming the diagnosis of malignant disease involving the pleura usually means incurable cancer.

Talc poudrage during the diagnostic thoracoscopy would be a reasonable approach to gain efficient pleurodesis and to reduce patient discomfort due to repeat thoracocenteses that would be necessary in the case of recurrent pleural effusion.

However, in most institutions instantaneous section histology is not available. Thus, a visual diagnosis of malignant pleural disease would be desirable. The aim of our study was to find out if it is possible to differentiate between benign and malignant pleural disease simply by evaluating pleural nodularity.

Results: Between 11/2006 and 10/2007 we performed 81 medical thoracoscopies. 41 patients had a benign disease of the pleura and 40 had a malignant disease of the pleura. Pleural nodularity was noted in one benign case (a singular node) and in 29 malignant cases (four with a singular node, eleven with some nodes, and 14 with many nodes). Sensitivity for malignancy with the visibility of nodules was 72,5% and specificity was 97,6%. The positive predictive value for malignancy with one visible node was 80% and with some or many nodes 100%.

Conclusions: Nodularity is a strong predictor of pleural malignancy. If some or many nodes are visible during medical thoracoscopy, immediate talc pleurodesis is justified. However, in about one quarter of the cases of pleural malignancy, no nodularity was noted and for these cases immediate talc poudrage cannot be recommendated.
Genotyping analyses of tuberculosis transmission among immigrant residents in Italy
Authors: F. Franzetti, L. Codecasa, A. Matteelli, A. Degli Esposti, A. Bandera, C. Lacchini, A. Lombardi, G. Pinsi, F. Zanini, I. El-Hamad, A. Gori
Journal: Clinical Microbiology and Infection (2009)
The effect of corticosteroid use on skeletal muscle function in patients with interstitial lung disease
Authors: Masatoshi Hanada, Noriho Sakamoto, Yuji Ishimatsu, Tomoyuki Kakugawa, Ryo Kozu, Hideaki Senjyu, Shigeru Kohno
Journal: European Respiratory Journal (2012)

Background and objective: Many patients with interstitial lung diseases (ILDs) may have reduced skeletal muscle strength. Corticosteroid as maintenance therapy are often used in these patients and known to have many side effects including muscle weakness. However, the effect of corticosteroid on skeletal muscle strength is uncertain. The purpose of this study was to examine the effect of maintenance corticosteroid use on skeletal muscle strength in patients with stable ILDs. Methods: Eighty-two ILDs patients were studied. Subjects were divided into with or without oral corticosteroid therapy, and skeletal muscle strength were evaluated. Results: Handgrip and quadriceps forces were less in patients taking corticosteroid than without steroid. There were significant correlations between % predicted quadriceps force and mean daily dose (r = -0.260, p = 0.019), duration (r = -0.276, p = 0.013), and total dosage (mean daily dose*duration, r = -0.289, p = 0.009) of corticosteroids use. Conclusions: Corticosteroid usage significantly affected skeletal muscle strength in patients with ILDs. Moreover, skeletal muscle weakness may be associated with increasing daily dose and duration of corticosteroids.
Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience.
Authors: B Fisher, H Rockette, E R Fisher, D L Wickerham, C Redmond, A Brown
Journal: Journal of Clinical Oncology (1985)

Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.
<i>CCR</i> 20th Anniversary Commentary: Expanding the Epigenetic Therapeutic Portfolio
Authors: Susan E. Bates, Robert W. Robey, Richard L. Piekarz
Journal: Clinical Cancer Research (2015)

Abstract Epigenetic targets have emerged as an exciting area for drug discovery. The discovery that histone deacetylase (HDAC) inhibitors had marked anticancer activity in T-cell lymphoma gave impetus to the field. In a phase I study published in Clinical Cancer Research in March 2002, romidepsin (depsipeptide), a potent HDAC inhibitor, was found to be tolerable, with a side effect profile that was later understood to be characteristic of this class of agents. Evidence of activity in this key phase I trial provided momentum for the further study of epigenetic agents. Clin Cancer Res; 21(10); 2195–7. ©2015 AACR. See related article by Sandor et al., Clin Cancer Res 2002;8(3) Mar 2002;718–28
The Agenda for Familial Hypercholesterolemia
Authors: Samuel S. Gidding, Mary Ann Champagne, Sarah D. de Ferranti, Joep Defesche, Matthew K. Ito, Joshua W. Knowles, Brian McCrindle, Frederick Raal, Daniel Rader, Raul D. Santos, Maria Lopes-Virella, Gerald F. Watts, Anthony S. Wierzbicki
Journal: Circulation (2015)
Infants with neuroblastoma and regional lymph node metastases have a favorable outlook after limited postoperative chemotherapy: a Pediatric Oncology Group study.
Authors: R P Castleberry, J J Shuster, G Altshuler, E I Smith, R Nitschke, N Winick, N McWilliams, V Joshi, F A Hayes
Journal: Journal of Clinical Oncology (1992)

PURPOSE Infants less than or equal to 1 year of age with neuroblastoma (NB) have a favorable outlook with minimal to moderate therapy. Patients with complete or partial removal of the primary tumor but positive intracavitary lymph nodes (Pediatric Oncology Group [POG] stage C) have a higher risk for recurrent disease. To determine the importance of distinguishing infants with POG stage C NB from those with POG stage B disease and to assess the efficacy and toxicity of treating POG stage C infants with limited, postoperative chemotherapy, a study was conducted by the POG. PATIENTS AND METHODS Forty-four eligible POG stage C infants received cyclophosphamide 150 mg/m2 orally on days 1 to 7 and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) 35 mg/m2 intravenously (IV) on day 8 (CYC/ADR), every 3 weeks for five courses followed by second-look surgery. No continuation therapy was given if surgical and pathologic complete response (CR) was achieved. Secondary therapy with five courses of cisplatin 90 mg/m2 on day 1 followed by teniposide (VM-26) 100 mg/m2 on day 3 (CDP/VM) was given to infants with gross residual tumor after CYC/ADR and second-look surgery. RESULTS Thirty-four infants achieved CR after CYC/ADR alone, three after CYC/ADR and second-look surgery, two after CYC/ADR, surgery, and maintenance therapy, and two after alternative treatment with CDP/VM (total CR rate, 42 of 44). The 3-year survival and disease-free survival are both 93%. Toxicity was nominal. CONCLUSIONS Infants with POG stage C NB have a favorable outlook, which is similar to infants with POG stage B NB; the surgical staging procedure for distinguishing these infant subsets may not be necessary. Future studies should focus on the reduction of treatment toxicity and efficacy maintenance, and address methods to identify infants at risk for failure.
Polypill Therapy, Subclinical Atherosclerosis, and Cardiovascular Events—Implications for the Use of Preventive Pharmacotherapy
Authors: Márcio Sommer Bittencourt, Michael J. Blaha, Ron Blankstein, Matthew Budoff, Jose D. Vargas, Roger S. Blumenthal, Arthur S. Agatston, Khurram Nasir
Journal: Journal of the American College of Cardiology (2013)
Treatment of staphylococcal prosthetic joint infections with debridement, prosthesis retention and oral rifampicin and fusidic acid
Authors: C.A. Aboltins, M.A. Page, K.L. Buising, A.W.J. Jenney, J.R. Daffy, P.F.M. Choong, P.A. Stanley
Journal: Clinical Microbiology and Infection (2007)
Impact of obesity on markers of asthma severity, control, health-related quality of life (HrQOL) and eosinophilia
Authors: Mithun Murthy, Indrani Karpha, Rajesh Yadavilli, Diana Lees, Hassan Burhan
Journal: European Respiratory Journal (2013)

Background: Asthma and obesity have a complex relationship. Some studies suggest higher incident asthma in obese patients, while others suggest risk of misdiagnosis (Scott S et al, Chest 2012;141:616-24). Higher BMI is linked to poorer HrQOL and asthma control (Lavoie K et al, Respir Med 2006;100:648-57).  Aim: To study influence of obesity on asthma severity (FEV1), blood eosinophils, Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) scores in patients attending a tertiary asthma clinic.  Methods: Retrospective review of patients (N=108) attending the Royal Liverpool difficult asthma service. Asthma diagnosed by specialists. Hypothesis testing using t-test & z-test.  Results: Mean (SD) age 49.3 (17.9) & BMI 30.0 (7.04).  Mean FEV1 was lower in obese asthmatics (2.3 V 2.0). No difference was seen in mean blood eosinophils between groups. However, significantly higher proportion of obese asthmatics had uncontrolled eosinophilia (26% V 13%). Obese patients also had worse AQLQ and ACT scores, both tending towards significance. A higher proportion of obese asthmatics were on step 5 treatment (33% V 21%).  Conclusions: In our study, obese asthmatics had worse HrQOL, asthma control and FEV1, with a higher proportion on BTS step 5 treatment. This may reflect greater severity in this group, but may also be due to loss of control.
Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites.
Authors: Z Yang
Journal: Molecular Biology and Evolution (1993)

Felsenstein's maximum-likelihood approach for inferring phylogeny from DNA sequences assumes that the rate of nucleotide substitution is constant over different nucleotide sites. This assumption is sometimes unrealistic, as has been revealed by analysis of real sequence data. In the present paper Felsenstein's method is extended to the case where substitution rates over sites are described by the gamma distribution. A numerical example is presented to show that the method fits the data better than do previous models.
Shortness of breath associated with chronic conditions among those with and without asthma or COPD
Authors: Joshua Lawson, Shelley Kirychuk, Rhonda Bryce, Punam Pahwa, Chandima Karunanayake, Louise Hagel, Donna Rennie, James Dosman
Journal: European Respiratory Journal (2012)

Background : Some chronic conditions may result from similar underlying mechanisms or may exacerbate lung disease suggesting the investigation of disease inter-relationships. We sought to determine if SOB was more common among adults with chronic conditions and to examine this association among those with and without asthma or COPD.   Methods : In 2010 we conducted a cross-sectional mail survey of rural households as part of the Saskatchewan Rural Health Study. One adult per home provided information about each adult living in the home. There were 8261 adults from 4624 households (42% participation) included. We examined the associations between reported diagnosed chronic conditions (diabetes, cardiovascular disease, and sleep apnea) and SOB after adjusting for potential confounders and stratifying by history of doctor-diagnosed asthma or COPD. High SOB was defined by a score of ≥3 on the MRC breathlessness scale.   Results : The respondents9 mean age was 56 years (SD=16 years) with 51% of the population being female. Approximately 14% had a MRC score ≥3. After adjustment, there was increased risk of high MRC score associated with the presence of diabetes [odds ratio (OR)=1.68, 95% confidence interval (CI)=1.32-2.14], cardiovascular disease (OR=2.18, 95%CI=1.80-2.65), and sleep apnea (OR=2.19, 95%CI=1.60-3.00). The associations with SOB were weaker among those with asthma or COPD with the exception of that for sleep apnea, which was stronger.   Conclusions : Some conditions were associated with high SOB among those with and without a history of lung disease. These relationships may result from common pathways, possibly inflammatory, and may precede more serious chronic lung disease.
Evaluation and modification of exercise patterns in the natural environment
Authors: Kelly D. Brownell, Albert J. Stunkard, Janet M. Albaum
Journal: American Journal of Psychiatry (1980)

Using a new experimental paradigm to evaluate physical activity in the natural environment, the authors made of 45,694 observations of persons using stairs or an adjacent escalator at a shopping mall, train station, and bus terminal. In study 1, stair use more than doubled for both obese and nonobese persons during two-week periods when a colorful sign encouraging use of the stairs was positioned at the stairs/escalator choice point. In study 2, stair use remained elevated for 15 consecutive days while the sign was present, decreased during a 1-month follow-up period, and returned to baseline by 3 months. These results not only demonstrate the usefulness of this paradigm, but also suggest the strength of simple, inexpensive public health interventions to increase physical activity.
Handgrip strength according to gender and COPD severity
Authors: Laura Caram, Renata Ferrari, Cristiane Naves, Mariana Ambrozi, Suzana Tanno, Andre Bertani, Liana Coelho, Irma Godoy
Journal: European Respiratory Journal (2011)

Decreased peripheral muscle strength has been shown in COPD patients; however a simple measure to evaluate this systemic manifestation is missing. The aim of this study was to compare the handgrip strength (HGS)between both genders and between patients with mild/moderate and severe/very severe COPD. Predictors of HGS were also evaluated. 25 mild/moderate COPD patients (68% male, age= 65±8 years, FEV1= 73±15%) and 25 severe/very severe COPD patients (56% male, age= 69±9 years, FEV1= 40±18%) were evaluated. Handgrip strength, pulse oximetry (SpO2), body mass index (BMI), six-minute walk distance (6MWD), Medical Research Council (MRC), Charlson comorbidity index and blood counts were obtained. Handgrip strength was significantly higher in mild/moderate COPD when compared to severe/very severe COPD (37±11kgf versus 31±10kgf; p=0.04), and was significantly higher in males when compared to women with COPD (39±10kgf versus 25±4kgf; p  FAPESP (2010/10312-1)