tbuckley/cabot-search huggingface dataset:
Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis
Authors: Margaret Rosenfeld, Philip M. Farrell, Margaret Kloster, Jonathan O. Swanson, Thuy Vu, Lyndia Brumback, James D. Acton, Robert G. Castile, Andrew A. Colin, Carol K. Conrad, Meeghan A. Hart, Gwendolyn S. Kerby, Peter W. Hiatt, Peter J. Mogayzel, Robin C. Johnson, Stephanie D. Davis
Journal: European Respiratory Journal (2013)

The optimal strategy for monitoring cystic fibrosis lung disease in infancy remains unclear. Our objective was to describe longitudinal associations between infant pulmonary function tests, chest radiograph scores and other characteristics. Cystic fibrosis patients aged ≤24 months were enrolled in a 10-centre study evaluating infant pulmonary function tests four times over a year. Chest radiographs ∼1 year apart were scored using the Wisconsin and Brasfield systems. Associations of infant pulmonary function tests with clinical characteristics were evaluated with mixed effects models. The 100 participants contributed 246 acceptable flow/volume (forced expiratory volume in 0.5 s (FEV<sub>0.5</sub>) and forced expiratory flow at 75% of the forced vital capacity (FEF<sub>75%</sub>)), 303 functional residual capacity measurements and 171 chest radiographs. Both Brasfield and Wisconsin chest radiograph scores worsened significantly over the 1-year interval. Worse Wisconsin chest radiograph scores and <i>Staphylococcus aureus</i> were both associated with hyperinflation (significantly increased functional residual capacity), but not with diminished FEV<sub>0.5</sub> or FEF<sub>75%</sub>. Parent-reported cough was associated with significantly diminished forced expiratory flow at 75% but not with hyperinflation. In this infant cohort in whom we previously reported worsening in average lung function, chest radiograph scores also worsened over a year. The significant associations detected between both Wisconsin chest radiograph score and <i>S. aureus</i> and hyperinflation, as well as between cough and diminished flows, reinforce the ability of infant pulmonary function tests and chest radiographs to detect early cystic fibrosis lung disease.
Unusual cause of a giant antral ulcer
Authors: Xiang-Yang Wang, Ying-Huan Dai, Yu-Ming Yang
Journal: Gut (2014)

<h3>Abstract</h3> Plant cell size and shape are tuned to their function and specified primarily by cellulose microfibril (CMF) patterning of the cell wall. <i>Arabidopsis thaliana</i> leaf trichomes are responsible for protecting plants against environmental elements and are unicellular structures that employ a highly anisotropic cellulose wall to extend and taper, generating pointed branches. During elongation, the mechanisms by which shifts in fiber orientation generate cells with predictable sizes and shapes are unknown. Specifically, the axisymmetric growth of trichome branches is often thought result from axisymmetric CMF patterning. Here, we analyzed the direction and degree of twist of branches after desiccation to reveal the presence of an asymmetric cell wall organization with a left-hand bias. CMF organization, quantified using computational modeling, suggests a limited reorientation of microfibrils during growth and maximum branch length limited by the wall axial stiffness. The model provides a mechanism for CMF asymmetry, which occurs after the branch bending stiffness becomes low enough that ambient bending affects the principal stresses. After this stage, the CMF synthesis results in a constant bending stiffness for longer branches. The resulting natural frequency of branches after a length of 200 μm falls within the range of the sounds associated with many insects. <h3>Statement of significance</h3> The growth of plant cell walls is governed by the direction of cellulose synthesis but the factors that influence the overall wall anisotropy are only partially understood. The twist of leaf trichome branches after desiccation reveals a left-handed asymmetry in cell wall organization even though the geometry is axisymmetric. This surprising behavior provides information about the directionality of cellulose synthesis control in plant cells.
Access to Diagnosis and Treatment of Patients with Suspected Sleep Apnea
Authors: W. Ward Flemons, Neil J. Douglas, Samuel T. Kuna, Daniel O. Rodenstein, John Wheatley
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; Respiratory Medicine, Royal Infirmary, Edinburgh, Scotland, United Kingdom; Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania; Pneumology Department, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium; and Department of Respiratory Medicine, Westmead Hospital, Wentworthville, New South Wales, Australia
Task Force on Strategic Research Direction
Authors: Robert Bonow, Edward B. Clark, Gregory D. Curfman, Alan Guttmacher, Martha N. Hill, D. Craig Miller, Aubrey R. Morrison, Robert J. Myerburg, Michael D. Schneider, Myron L. Weisfeldt, James T. Willerson, James B. Young
Journal: Circulation (2002)

Perhaps large population studies will allow us to understand these polymorphisms and give greater insight into the importance
Calcium Plus Vitamin D Supplementation and the Risk of Incident Diabetes in the Women's Health Initiative
Authors: Ian H. de Boer, Lesley F. Tinker, Stephanie Connelly, J. David Curb, Barbara V. Howard, Bryan Kestenbaum, Joseph C. Larson, JoAnn E. Manson, Karen L. Margolis, David S. Siscovick, Noel S. Weiss
Journal: Diabetes Care (2008)

OBJECTIVE—Experimental and epidemiologic studies suggest that calcium and vitamin D may reduce the risk of developing diabetes. We examined the effect of calcium plus vitamin D supplementation on the incidence of drug-treated diabetes in postmenopausal women. RESEARCH DESIGN AND METHODS—The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned postmenopausal women to receive 1,000 mg elemental calcium plus 400 IU of vitamin D3 daily, or placebo, in a double-blind fashion. Among 33,951 participants without self-reported diabetes at baseline, we ascertained by treatment assignment new diagnoses of diabetes treated with oral hypoglycemic agents or insulin. Effects of the intervention on fasting measurements of glucose, insulin, and insulin resistance were examined among a subset of participants. RESULTS—Over a median follow-up time of 7 years, 2,291 women were newly diagnosed with diabetes. The hazard ratio for incident diabetes associated with calcium/vitamin D treatment was 1.01 (95% CI 0.94–1.10) based on intention to treat. This null result was robust in subgroup analyses, efficacy analyses accounting for nonadherence, and analyses examining change in laboratory measurements. CONCLUSIONS—Calcium plus vitamin D3 supplementation did not reduce the risk of developing diabetes over 7 years of follow-up in this randomized placebo-controlled trial. Higher doses of vitamin D may be required to affect diabetes risk, and/or associations of calcium and vitamin D intake with improved glucose metabolism observed in nonrandomized studies may be the result of confounding or of other components of foods containing these nutrients.
Reply to T.H. Oude Munnink et al
Authors: Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2010)

We applaud this letter 1 to the editor commenting on our recent publication. 2It comes from a group who have been pioneers in demonstrating that whole-body imaging with radiolabeled trastuzumab can provide quantitative data on trastuzumab tumor uptake and organ distribution in addition to blood pool levels.We fully acknowledge that deriving optimal trastuzumab loading and dosing regimens have their limits and that optimal trastuzumab dosing will benefit from individualization of therapy.Here, Oude Munnink et al 1 examine the effect of high tumor burden on individual trastuzumab clearance, but also comment on the excellent Bruno et al 3 article relating to high human epidermal growth factor receptor-2 extracellular domain plasma levels.In the era of personalized medicine, where targeted therapies will be matched to the patient's genetic and phenotypic profile, this reminds us that dosing of these therapies must also be matched to the individual's pharmokinetic functions, to include consideration of both organ function and tumor burden.
Outcome of Pregnancy and Disease Course among Women with Aplastic Anemia Treated with Immunosuppression
Authors: André Tichelli
Journal: Annals of Internal Medicine (2002)

Background: Aplastic anemia may develop during pregnancy and sometimes improves spontaneously after delivery. The effects of pregnancy on aplastic anemia after immunosuppressive treatment and of aplastic anemia on the outcome of pregnancy have not been described. Objective: To determine the outcome of pregnancy and the disease course among women with aplastic anemia who received immunosuppressive therapy. Design: Retrospective multicenter study. Setting: Twelve centers participating in the European Group for Blood and Marrow Transplantation. Patients: 36 women who received immunosuppressive therapy to treat aplastic anemia. Measurements: Outcomes of pregnancy and aplastic anemia and blood counts before, during, and after delivery. Results: The 36 pregnancies resulted in 34 live births (one set of twins), 2 elective abortions, and 1 spontaneous abortion. Of the 36 pregnancies, 22 were uncomplicated and 14 involved medical complications. Seven pregnancies (19%) were complicated by relapse of aplastic anemia, and 5 patients without relapse (14%) needed transfusions during delivery. After delivery, 3 of the 7 patients who had relapse recovered spontaneously and 3 recovered after retreatment. One patient who did not respond to treatment died of aplastic anemia. A woman with aplastic anemia and paroxysmal nocturnal hemoglobinuria had a fatal cerebral thrombosis after delivery. Women with uneventful pregnancies had better prepregnancy remission status (8 complete and 11 partial remissions) and a higher median platelet count (146 × 109 cells/L) than did women with complicated pregnancies (2 complete remissions, 8 partial remissions, and 4 cases of paroxysmal nocturnal hemoglobinuria; median platelet count, 92 × 109 cells/L). Conclusions: Successful pregnancy with normal outcome is possible in women with aplastic anemia previously treated with immunosuppression. Complications appear to be more likely in patients with low platelet counts and paroxysmal nocturnal hemoglobinuria–associated aplastic anemia. *For a list of centers that participated in the Study of the European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party, see Appendix.
Bendamustine Plus Rituximab Is Effective and Has a Favorable Toxicity Profile in the Treatment of Mantle Cell and Low-Grade Non-Hodgkin's Lymphoma
Authors: Mathias J. Rummel, Salah E. Al-Batran, Soo-Z. Kim, Manfred Welslau, Ralf Hecker, Dorothea Kofahl-Krause, Klaus-M. Josten, Heinz Dürk, Andreas Rost, Michael Neise, Ulrich von Grünhagen, Kai U. Chow, Martin-L. Hansmann, Dieter Hoelzer, Paris S. Mitrou
Journal: Journal of Clinical Oncology (2005)

Purpose The aim of this multicenter-study was to evaluate the progression-free survival, response rate and toxicity of the combination of bendamustine and rituximab (BR) in patients with mantle cell or low-grade lymphomas in first to third relapse or refractory to previous treatment. Patients and Methods A total of 245 courses (median, four courses per patient) were administered to 63 patients. Bendamustine was given at a dose of 90 mg/m 2 as a 30-minute infusion on days 1 and 2, combined with 375 mg/m 2 rituximab on day 1, for a maximum of four cycles every 4 weeks. Histologies were 24 follicular, 16 mantle cell, 17 lymphoplasmacytoid, and six marginal zone lymphoma. Results Fifty-seven of 63 patients responded to BR, corresponding to an overall response rate of 90% (95% CI, 80% to 96%) with a complete remission rate (CR) of 60% (95% CI, 47% to 72%). The median time of progression-free survival was 24 months (range, 5 to 44+ months), and the median duration of overall survival has not yet been reached. In mantle cell lymphomas, BR showed a considerable activity, achieving a response rate of 75% (95% CI, 48% to 93%) with a CR rate of 50%. Myelosuppression was the major toxicity, with 16% grade 3 and 4 leukocytopenia. Thrombocytopenia was rare, with only 3% grade 3 and 4. Conclusion These results demonstrate that the BR combination is a highly active regimen in the treatment of low-grade lymphomas and mantle cell lymphomas.
Unpicking the Combination Lock for Mutant BRAF and RAS Melanomas
Authors: Bissan Al-Lazikani, Paul Workman
Journal: Cancer Discovery (2013)

Abstract Summary: Large-scale, unbiased combinatorial drug screening has been used to identify effective genotype-selective therapeutic combinations that show promising activity in preclinical models of mutant BRAF andRAS melanoma that are resistant to the clinical BRAF inhibitor vemurafenib. Cancer Discov; 3(1); 14–9. ©2012 AACR. See related article by Held et al., p. 52
Fluorodeoxyglucose Positron Emission Tomography for the Preoperative Staging of Oral Cavity Cancers: Only One Piece of the Puzzle
Authors: John N. Waldron
Journal: Journal of Clinical Oncology (2006)

At present, the potential uses for positron emission tomography (PET) in the management of cancer include the characterization of disease at presentation, assessment of disease response to treatment, and the detection of recurrent disease. Published reports of the use of PET in cancer patients listed in the PubMed databasehavemultipliedbyafactorof10overthelastdecade,with close to 1,000 reports in 2005. It is reasonable to conclude that, for the majority of patients at presentation who undergo staging with computed tomography (CT) and/or magnetic resonance imaging (MRI), the use of fluorodeoxyglucose (FDG) PET does not add information that would change initial management. Nonetheless, FDG-PET will detect disease that would have been otherwise overlooked for an important minority of patients.Theconsequenceshouldpreventundertreatmentinthecase ofspecificallytargetedtherapiessuchassurgeryorradiation.Alternatively,whenFDG-PETdeterminesthatdiseasehasspreadbeyondthe possibility of curative treatments, the morbidity of overtreatment will
Cytokines present in smokers' serum interact with smoke components to enhance endothelial dysfunction
Authors: Silvia S. Barbieri, Elena Zacchi, Patrizia Amadio, Sara Gianellini, Luciana Mussoni, Babette B. Weksler, Elena Tremoli
Journal: Cardiovascular Research (2011)

AimsCigarette smoking engenders inflammation and endothelial dysfunction, processes implicated in atherothrombotic disease. We hypothesized that an interaction between inflammatory cytokines in smokers' blood and circulating components of cigarette smoke is necessary to induce reactive oxygen species (ROS) and cyclooxygenase-2 (COX-2) in endothelium. We then explored the molecular mechanisms involved in these effects.
Does Comorbidity Account for the Excess Mortality in Patients With Major Bleeding in Acute Myocardial Infarction?
Authors: Frederick A. Spencer, Mauro Moscucci, Christopher B. Granger, Joel M. Gore, Robert J. Goldberg, Philippe Gabriel Steg, Shaun G. Goodman, Andrzej Budaj, Gordon FitzGerald, Keith A.A. Fox
Journal: Circulation (2007)

Background— Analyses from randomized controlled trials suggest that bleeding in patients with acute myocardial infarction is associated with poor outcomes. Because these data are not generalizable to all patients with acute myocardial infarction, we sought to better understand the scope of this problem in a “real-world” setting. Methods and Results— We examined the frequency of major bleeding in 40 087 patients with acute myocardial infarction enrolled in the Global Registry of Acute Coronary Events. Regression analyses were used to examine the association between patient and treatment characteristics, bleeding, and hospital and postdischarge outcomes. Major bleeding occurred in 2.8% of patients. These patients were older, more severely ill, and more likely to undergo invasive procedures. Patients with bleeding were more likely to die during hospitalization (hazard ratio, 1.9; 95% confidence interval, 1.6 to 2.2) but not after discharge (hazard ratio, 0.8; 95% confidence interval, 0.6 to 1.0) than patients who did not bleed. Continuation of antithrombotic therapies after day 1 was lower in patients who experienced early bleeding. Moreover, in patients who bled, hospital mortality was increased in those who discontinued aspirin, thienopyridines, or low–molecular-weight heparins. Conclusions— Major bleeding occurred in 1 in 35 patients with acute myocardial infarction; these patients accounted for ≈10% of all hospital deaths. Nevertheless, risk of hospital mortality associated with bleeding was much lower than reported in randomized controlled trials. These data suggest that although bleeding may be causally related to adverse outcomes in some patients in the real-world setting, it is often merely a marker for patients at higher risk for adverse outcomes.
Hot off the breath: ‘I've a cost for’—the 64 million dollar question: Table 1
Authors: Andrew Bush, Nicholas J Simmonds
Journal: Thorax (2012)

obliterative process in the smallest of the conducting airways and the inflammatory/ fibrotic process that thickens and narrows the larger airways that are visible on CT.In summary, the results of Martinez et al 1 raise important questions about the relationship between structural changes in the lung, abnormalities of lung function and respiratory related symptoms, physical activity and psychosocial impacts.It is somewhat paradoxical that the authors chose to compare more precise morphological features of COPD with composite measures of function and symptoms since the COPD community is striving to separate subphenotypes of COPD based on pathogenetic mechanisms and structural changes.However, by identifying the relationships between these CT features and the components of the composite scores, the authors have allowed us to more precisely determine their relationship to CT features and in so doing have raised important issues.
Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia
Authors: Robert T. Eberhardt, Marc A. Forgione, Andre Cap, Jane A. Leopold, M. Audrey Rudd, Maria Trolliet, Stanley Heydrick, Rachel Stark, Elizabeth S. Klings, Nicanor I. Moldovan, Mohammed Yaghoubi, Pascal J. Goldschmidt-Clermont, Harrison W. Farber, Richard Cohen, Joseph Loscalzo
Journal: Journal of Clinical Investigation (2000)

Homocysteine is a risk factor for the development of atherosclerosis and its thrombotic complications. We have employed an animal model to explore the hypothesis that an increase in reactive oxygen species and a subsequent loss of nitric oxide bioactivity contribute to endothelial dysfunction in mild hyperhomocysteinemia. We examined endothelial function and in vivo oxidant burden in mice heterozygous for a deletion in the cystathionine β-synthase (CBS) gene, by studying isolated, precontracted aortic rings and mesenteric arterioles in situ. CBS–/+ mice demonstrated impaired acetylcholine-induced aortic relaxation and a paradoxical vasoconstriction of mesenteric microvessels in response to superfusion of methacholine and bradykinin. Cyclic GMP accumulation following acetylcholine treatment was also impaired in isolated aortic segments from CBS–/+ mice, but aortic relaxation and mesenteric arteriolar dilation in response to sodium nitroprusside were similar to wild-type. Plasma levels of 8-epi-PGF2α (8-IP) were somewhat increased in CBS–/+ mice, but liver levels of 8-IP and phospholipid hydroperoxides, another marker of oxidative stress, were normal. Aortic tissue from CBS–/+ mice also demonstrated greater superoxide production and greater immunostaining for 3-nitrotyrosine, particularly on the endothelial surface. Importantly, endothelial dysfunction appears early in CBS–/+ mice in the absence of structural arterial abnormalities. Hence, mild hyperhomocysteinemia due to reduced CBS expression impairs endothelium-dependent vasodilation, likely due to impaired nitric oxide bioactivity, and increased oxidative stress apparently contributes to inactivating nitric oxide in chronic, mild hyperhomocysteinemia.
Stopping Trials Early for Positive Results: The Need to Know How Much
Authors: Carl D. Atkins
Journal: Journal of Clinical Oncology (2009)

TO THE EDITOR: It is reassuring that Korn et al have been able to show that stopping or early reporting of results in randomized clinical trials by the National Cancer Institute Cooperative Groups has generally not led to the kind of biased results noted by Wilcox et al that lead to type I errors. However, Korn et al admit, “Concerns about biased treatment effects as a result of the early stopping are statistically valid.” They go on to state that “releasing information early about an effective treatment may be more important than knowing the exact magnitude of the benefit.” Here I must respectfully disagree. They nicely elucidate in their section “Choice of Primary End Point” the difficulties raised by the use of surrogate end points and the effect of crossovers to the experimental arm after early stopping of a trial. A prime example of the problem is the Tamoxifen Prevention Trial, which was stopped early because the primary end point—breast cancer incidence—crossed a prespecified boundary. On follow-up, after treatment crossovers to the experimental arm, no benefit has yet been demonstrated in overall or breast cancer–specific survival. Significant toxicities to otherwise healthy women were documented, including rare cases of uterine cancer and somewhat less rare cases of thromboembolism. If the estimate of benefit is biased, how important is it to know that treatment of the overall population (with varied risks) was beneficial compared with no treatment? How are prospective patients supposed to determine the value of treatment? Would not more precise information assist me in helping a 50-year-old woman who is worried about blood clots make such a decision? Sometimes we need a trial to tell us that an experimental arm is better than its comparator. More often we need to know how much better.
FUT2 and FUT3 genotype determines CA19-9 cut-off values for detection of cholangiocarcinoma in patients with primary sclerosing cholangitis
Authors: Andreas Wannhoff, Johannes Roksund Hov, Trine Folseraas, Christian Rupp, Kilian Friedrich, Jarl Andreas Anmarkrud, Karl Heinz Weiss, Peter Sauer, Peter Schirmacher, Kirsten Muri Boberg, Wolfgang Stremmel, Tom Hemming Karlsen, Daniel Nils Gotthardt
Journal: Journal of Hepatology (2013)