tbuckley/cabot-search huggingface dataset:
Prevalence of chronic respiratory symptoms, ventilatory capacity and bronchial responsiveness in welders
Authors: Saso Stoleski, Jovanka Karadzinska Bislimovska, Jordan Minov, Dragan Mijakoski, Snezana Ristetska Kuc
Journal: European Respiratory Journal (2012)

Objective: To evaluate the prevalence of chronic respiratory symptoms, ventilatory capacity abnormalities and bronchial hyperresponsivness in welders and to clarify the role of workplace exposure. Methods: A cross sectional study was performed including 40 males working as stainless steel welders (mean age=43.9±7.4; duration of exposure 15.2±6.8 yrs) and 40 male office workers as a control group (mean age=42.8±7.1) matched for age, duration of employment, smoking habits and socioeconomic status. Evaluation of examined subjects included completion of a questionnaire on respiratory symptoms in the last 12 months (cough, phlegm, dyspnea, wheezing, and chest tightness), spirometry and histamine challenge (PC20≤8 mg/mL). Results: We found non-significantly higher prevalence of respiratory symptoms in the last 12 months in welders with significant difference for cough (P=0.036) and phlegm (P=0.007). Mean values of spirometric parameters was lower in welders with significant difference for MEF25 (P=0.006) and MEF75 (P=0.000). Prevalence of bronchial hyperresponsiveness (BHR) was higher in welders with significant difference for borderline BHR (P=0.041). Multivariate analysis showed that current smoking (OR=8.4, 1.6 to 81.7) and total exposure to welding fumes with duration of more than 10 years (OR=8.2, 1.7 to 69.8) were independent risk factors for development of chronic respiratory symptoms. Conclusion: Our data suggest that workplace exposure in welders may lead to respiratory impairment that on the other hand is closely related to its duration.
Cancer-Induced Immunosuppression: IL-18–Elicited Immunoablative NK Cells
Authors: Magali Terme, Evelyn Ullrich, Laetitia Aymeric, Kathrin Meinhardt, Jérôme D. Coudert, Mélanie Desbois, François Ghiringhelli, Sophie Viaud, Bernard Ryffel, Hideo Yagita, Lieping Chen, Salaheddine Mécheri, Gilles Kaplanski, Armelle Prévost-Blondel, Masashi Kato, Joachim L. Schultze, Eric Tartour, Guido Kroemer, Mariapia Degli-Esposti, Nathalie Chaput, Laurence Zitvogel
Journal: Cancer Research (2012)

During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression in NK cell-controlled cancers, the mechanistic cues underlying this immunosuppression remain unknown. Here, we show that IL-18 converts a subset of Kit(-) (CD11b(-)) into Kit(+) natural killer (NK) cells, which accumulate in all lymphoid organs of tumor bearers and mediate immunoablative functions. Kit(+) NK cells overexpressed B7-H1/PD-L1, a ligand for PD-1. The adoptive transfer of Kit(+) NK cells promoted tumor growth in two pulmonary metastases tumor models and significantly reduced the dendritic and NK cell pools residing in lymphoid organs in a B7-H1-dependent manner. Neutralization of IL-18 by RNA interference in tumors or systemically by IL-18-binding protein dramatically reduced the accumulation of Kit(+)CD11b(-) NK cells in tumor bearers. Together, our findings show that IL-18 produced by tumor cells elicits Kit(+)CD11b(-) NK cells endowed with B7-H1-dependent immunoablative functions in mice.
Serum interleukin 5 concentrations in atopic and non-atopic patients with glucocorticoid-dependent chronic severe asthma.
Authors: A G Alexander, J Barkans, R Moqbel, N C Barnes, A B Kay, C J Corrigan
Journal: Thorax (1994)

BACKGROUND--Interleukin (IL)-5 is thought to play a part in asthmatic bronchial mucosal inflammation and is a potential therapeutic target. Detectable serum IL-5 concentrations have been found previously in a proportion of patients with acute severe asthma, but not in the same patients following oral glucocorticoid therapy or in normal controls. A study was undertaken to investigate whether or not IL-5 is detectable in the serum of patients with glucocorticoid-dependent chronic severe asthma. METHODS--Serum concentrations of IL-5 were measured in 29 patients with stable oral glucocorticoid-dependent chronic severe asthma (mean PEFR 59.7% predicted) and seven normal controls using a specific enzyme-linked immunoassay calibrated with recombinant human IL-5 standards (lower limit of sensitivity 40 pg/ml). RESULTS--Interleukin 5 was detectable in the serum of 15 of the 29 patients at a median concentration of 150 pg/ml (range 40-690), but was undetectable in the serum of all the control subjects. The patients with detectable serum IL-5 concentrations did not differ from those with undetectable concentrations in terms of atopic status, disease severity (percentage predicted PEFR or FEV1), prednisolone dosage, serum IgE concentrations, or peripheral eosinophil count. CONCLUSIONS--Interleukin 5 is detectable in the serum of a proportion of both atopic and non-atopic patients with chronic severe asthma, and concentrations in these patients were higher than in normal controls. These observations are compatible with the hypothesis that IL-5 release occurs in these patients during a period of stable asthma despite systemic glucocorticoid therapy.
Influence of Extracellular Potassium Concentration on Myocardial Uptake and Inotropic Effect of Tritiated Digoxin
Authors: KIRK H. PRINDLE, C. LYNN SKELTON, STEPHEN E. EPSTEIN, FRANK I. MARCUS
Journal: Circulation Research (1971)

Because of conflicting reports on the influence of extracellular potassium concentration ([K] 0 ) on the inotropic action of cardiac glycosides, we compared the effects of varying [K] 0 (1.5, 4.5, and 7.5m M ) on the inotropic action and myocardial concentration of tritiated digoxin (5 x 10 -7 M ) using the isolated cat papillary muscle. The time course of the inotropic response to digoxin was significantly altered by [K] 0 in an inverse manner; the rate of change of the active tension response to digoxin (g/mm 2 · min -1 ) was 0.048±0.004 with low [K] 0 , 0.025±0.003 with normal [K] 0 and 0.014±0.002 with high [K] 0 . There were no differences, however, in the peak inotropic responses achieved at each [K] 0 . Muscles were analyzed for 3 H-digoxin content after 45 minutes, and at the time of the peak inotropic response. The relationships found between [K] 0 and 3 H-digoxin content were similar to those found between [K] 0 and active tension. Moreover, a significant positive correlation between digoxin content and the increment in active tension was observed. Thus, an inverse relationship exists between [K] 0 and the rate of development of the inotropic response to digoxin, changes that may be due to a [K] 0 induced alteration in myocardial digoxin content.
A Source of False Findings in Published Research Studies
Authors: Helena Chmura Kraemer
Journal: JAMA Psychiatry (2015)

Concern about erroneous conclusions of many published research findings has led to the conclusion that most published research findings are wrong. 1,2What can be done about that?In what follows, I will focus on one common source of false findings: adjusting for covariates.Here, adjusting means allowing variables to vary as they will but then using a mathematical model to assess their influence on the outcome.In contrast, to control means manipulation of variables by the researcher for a particular purpose (eg, in experimental design).Unfortunately, the terms adjust and control are often used as if they were synonymous.Adjusting often leads to false conclusions because the models used may not correspond to reality.To illustrate this point, consider a randomized clinical trial (RCT) in which those sampled from the population of interest are randomly assigned to 2 treatment groups, T1 and T2.A valid test simply comparing the outcomes in the 2 groups tests the overall effect size (overall ES) that a randomly sampled patient from T1 has an outcome clinically preferable to that of a randomly sampled patient from T2. 3 Often, the first table of an RCT report compares the baseline characteristics of the T1 vs T2 samples to assess the success of randomization, ignoring the fact that randomization (1) is a process, not an outcome, and (2) is meant to generate 2 random samples from the same population, not 2 matched samples.When a few baseline variables significantly differentiate the 2 groups at the 5% level, researchers often propose to adjust for those covariates in testing the treatment effect.This is post hoc testing (like offering to bet at prerace odds on a horse as it approaches the finish line), which frequently leads to false-positive results.Any covariates to be used in adjusting should be specified a priori, listed in the RCT registration, and taken into consideration in the power analysis.Such adjustment changes the hypothesis to be tested from comparing all T1 patients vs all T2 patients (overall ES) to comparing T1 patients only with T2 patients matched in one way or another on the particular covariates proposed.Let's say that covariate ES is the ES for patients with one particular configuration of the covariates and typical ES is the ES specifically for patients who are at the mean of each such covariate (ie, for the typical patient).Overall ES, typical ES, and all possible covariate ES are the same only if the covariates are irrelevant to the treatment outcome.If the covariates are irrelevant, adjusting for those simply leads to a loss of power.If the covariates are not irrelevant, then estimation and testing of overall ES, typical ES, and covariate ES provide answers to different research questions.
CD8<sup>+</sup>T Cells Provide an Immunologic Signature of Tuberculosis in Young Children
Authors: Christina Lancioni, Melissa Nyendak, Sarah Kiguli, Sarah Zalwango, Tomi Mori, Harriet Mayanja-Kizza, Stephen Balyejusa, Megan Null, Joy Baseke, Deo Mulindwa, Laura Byrd, Gwendolyn Swarbrick, Christine Scott, Denise F. Johnson, LaShaunda Malone, Philipa Mudido-Musoke, W. Henry Boom, David M. Lewinsohn, Deborah A. Lewinsohn
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD8(+) T cells are generated in response to high bacillary loads occurring during tuberculosis.To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis.Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M. tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8(+) T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62).The proportion of positive CD8(+) T-cell assays and magnitude of CD8(+) T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups.Among young children, M. tuberculosis-specific CD8(+) T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ-producing M. tuberculosis-specific CD8(+) T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease.
Experience before Medical School
Authors: Piyasakol Sakolsatayadorn
Journal: Journal of the Royal Society of Medicine (2001)

In the JRSM last year, Sir David Weatherall1 expressed concern about the narrow education of young people who enter medical school. One aspect is the possibility that they have chosen the wrong career and will eventually drop out.

The decision to study medicine is influenced by parents, teachers, friends or society. Many applicants do not completely understand the responsibilities of physicians and cannot be sure they are suited to the profession. A knowledge of how medical personnel work in a hospital will help them make a good decision. In the academic year 2000, the Faculty of Medicine Siriraj Hospital declared that the 115 students selected by the Faculty and the other 115 students selected by the Ministry of University Affairs must have at least 10 days' experience in assisting the services of government hospitals. The 10 days do not need to be consecutive, must be completed during 10th-12th grade, and may be performed on either weekdays or weekends. It is up to the director of the individual hospital to consider how to optimize the student's individual experience. It is also at the discretion of the director to arrange work in the hospital for the students—to feed and converse with patients, retrieve patients in the outpatient setting, write transfer orders, assist doctors examining or treating the patients and so on. Students who live in provincial areas can contact hospitals near their homes while those who live in the Bangkok Metropolitan area can work at Siriraj Hospital.

When students complete their experience in the hospital, they will receive a certificate from the hospital director. They will then be asked to submit this certificate along with all required documents when they apply to take the entrance examination organized by the Faculty and by the Ministry of University Affairs. The Faculty has been developing this project for eight years with successful results.

From personal experience I can say that this project is successful. My second daughter was keen to study medicine and applied for this project; however, after only three days of experience she realized that the medical profession was not for her, and she is now a successful accountant. My youngest daughter likewise entered the project and loved it. She is now a fourth year medical student with a good academic record.
Low Initial Human Papilloma Viral Load Implicates Worse Prognosis in Patients With Uterine Cervical Cancer Treated With Radiotherapy
Authors: Joo-Young Kim, Sohee Park, Byung-Ho Nam, Ju-Won Roh, Chae Hyeong Lee, Yoon-Hee Kim, Hye-Jin Shin, Su-Kyoung Lee, Sun-Young Kong, Moon-Woo Seong, Tae-Jin Han, Me-Yeon Lee, Kwan Ho Cho, Sang Yoon Park
Journal: Journal of Clinical Oncology (2009)

Purpose To evaluate whether human papillomavirus (HPV) viral load measured in cervical smear and HPV type 18 are associated with radiotherapy outcomes in uterine cervical cancer. Patients and Methods HPV DNA was semiquantitatively measured in the cervical smears of 169 radiotherapy patients. HPV viral load was classified as low or high according to median HPV DNA titer and examined for its prognostic value. The multivariable Cox proportional hazards model was used to adjust for covariates. A relapse-predicting model was constructed to classify three risk groups for disease-free survival (DFS), which were used for internal validation. Results Patients with lower HPV viral load showed worse DFS in univariate analysis. HPV type 18, younger patient age, stage group, nodal status, histologic grade, and histologic type were other prognostic factors for poor DFS. Among these factors, all except stage group were associated with HPV viral load. Multivariate analysis showed the strong influence of HPV viral load for poor DFS. The prognostic model developed using our outcome data performed well in predicting the risk of relapse. Conclusion Our data suggest that HPV viral load is a strong independent prognostic factor for DFS. HPV type 18 showed a significant relationship with poor radiotherapy outcome in univariate analysis, but not in multivariate analysis.
Superiority of Icodextrin Compared with 4.25% Dextrose for Peritoneal Ultrafiltration
Authors: Fredric Finkelstein, Helen Healy, Ali Abu-Alfa, Suhail Ahmad, Fiona Brown, Todd Gehr, Kevin Nash, Michael Sorkin, Salim Mujais
Journal: Journal of the American Society of Nephrology (2005)

Several clinical observations suggest the superiority of icodextrin compared with 4.25% dextrose in optimizing peritoneal ultrafiltration (UF), but no rigorous controlled evaluation has hitherto been performed. For comparing icodextrin and 4.25% dextrose during the long dwell of automated peritoneal dialysis, a multicenter, randomized, double-blind trial was conducted in 92 patients (control, 45; icodextrin, 47) with 4-h dialysate to plasma ratio creatinine >0.70 and D/D(0) glucose <0.34. Long-dwell net UF and the UF efficiency ratio (net UF volume per gram of dialysate carbohydrate absorbed) were determined at baseline, week 1, and week 2. The control and treatment groups were comparable at baseline (all patients using 4.25% dextrose for the long dwell) with regard to mean (+/-SEM) net UF (201.7 +/- 103.1 versus 141.6 +/- 75.4 ml, respectively; P = 0.637) and the percentage of patients with negative net UF (control, 37.8%; treatment, 42.6%; P = 0.641). During the study period, net UF was unchanged from baseline in the control group but increased significantly (P < 0.001) in the icodextrin group from 141.6 +/- 75.4 to 505.8 +/- 46.8 ml at week 1 and 540.2 +/- 46.8 ml at week 2. In the icodextrin group, the incidence of negative net UF was significantly lower (P < 0.0001) than in the control group. Findings were similar for UF efficiency ratio. Rash was reported significantly more often in the icodextrin group. This study showed that in high-average and high transporters, icodextrin is superior to 4.25% dextrose for long-dwell fluid and solute removal.
TFE3 transcriptionally activates hepatic IRS-2, participates in insulin signaling and ameliorates diabetes
Authors: Yoshimi Nakagawa, Hitoshi Shimano, Tomohiro Yoshikawa, Tomohiro Ide, Mariko Tamura, Mika Furusawa, Takashi Yamamoto, Noriyuki Inoue, Takashi Matsuzaka, Akimitsu Takahashi, Alyssa H Hasty, Hiroaki Suzuki, Hirohito Sone, Hideo Toyoshima, Naoya Yahagi, Nobuhiro Yamada
Journal: Nature Medicine (2005)
Pulmonary effects of short-term exposure to low levels of toluene diisocyanate in asymptomatic subjects
Authors: O. Vandenplas, J.-P. Delwiche, P Staquet, J Jamart, A Bernard, J Boulanger, L. Delaunois, Y. Sibille
Journal: European Respiratory Journal (1999)

Isocyanates may be involved in the development of chronic obstructive airway disease among exposed workers. A short-term exposure to toluene diisocyanate (TDI) at concentrations near the permissible levels was investigated to examine whether there was an association with changes in pulmonary function tests and in potential markers of airway injury and inflammation in bronchial lavage (BL) and bronchoalveolar lavage (BAL). Seventeen subjects without respiratory symptoms (eight smokers and nine nonsmokers) were exposed once to ambient air and once to TDI (5 parts per billion (ppb) for 6 h followed by 20 ppb for 20 min) in a randomized, single-blind sequence. Pulmonary function tests were repeatedly assessed during exposure and BAL was performed 1 h after each exposure. Biochemical studies on lavage fluids included albumin, immunoglobulins, antiproteases (alpha2-macroglobulin and alpha1-proteinase inhibitor), potential indicators of epithelial cell function (secretory component and Clara cell protein), and cytokines (tumour necrosis factor-alpha, interleukin (IL)-4, IL-5, IL-6, and IL-8). Exposure to TDI caused a modest decrease in specific airway conductance (sGaw) (p=0.053) and in maximal expiratory flow at 25% of forced vital capacity (MEF25%) (p=0.015) when compared with ambient air. Exposure to TDI resulted in a slight increase in BAL albumin level (TDI: 26.4+/-12.5 versus air: 21.8+/-8.6 microg x mL(-1), p=0.044) and in BL alpha2-macroglobulin concentration (TDI: 0.07+/-0.061 versus air: 0.05+/-0.04 microg x mL(-1), p=0.021). This study suggests that exposure to low toluene disocyanate concentrations is associated with minimal but detectable changes in airway calibre and in epithelial barrier permeability. The pulmonary effects of long-term exposure to low levels of isocyanates require further investigation.
Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation
Authors: Marcos de Lima, Athanasios Anagnostopoulos, Mark Munsell, Munir Shahjahan, Naoto Ueno, Cindy Ippoliti, Borje S. Andersson, James Gajewski, Daniel Couriel, Jorge Cortes, Michele Donato, Joyce Neumann, Richard Champlin, Sergio Giralt
Journal: Blood (2004)
Combination of Antibody That Inhibits Ligand-Independent HER3 Dimerization and a p110α Inhibitor Potently Blocks PI3K Signaling and Growth of HER2+ Breast Cancers
Authors: Joan T. Garrett, Cammie R. Sutton, Richard Kurupi, Carl Uli Bialucha, Seth A. Ettenberg, Scott D. Collins, Qing Sheng, Jerry Wallweber, Lisa DeFazio-Eli, Carlos L. Arteaga
Journal: Cancer Research (2013)

Abstract We examined the effects of LJM716, an HER3 (ERBB3) neutralizing antibody that inhibits ligand-induced and ligand-independent HER3 dimerization, as a single agent and in combination with BYL719, an ATP competitive p110α-specific inhibitor, against HER2-overexpressing breast and gastric cancers. Treatment with LJM716 reduced HER2-HER3 and HER3-p85 dimers, P-HER3 and P-AKT, both in vitro and in vivo. Treatment with LJM716 alone markedly reduced growth of BT474 xenografts. The combination of LJM716/lapatinib/trastuzumab significantly improved survival of mice with BT474 xenografts compared with lapatinib/trastuzumab (P = 0.0012). LJM716 and BYL719 synergistically inhibited growth in a panel of HER2+ and PIK3CA mutant cell lines. The combination also inhibited P-AKT in HER2-overexpressing breast cancer cells and growth of HER2+ NCI-N87 gastric cancer xenografts more potently than LJM716 or BYL719 alone. Trastuzumab-resistant HER2+/PIK3CA mutant MDA453 xenografts regressed completely after 3 weeks of therapy with LJM716 and BYL719, whereas either single agent inhibited growth only partially. Finally, mice with BT474 xenografts treated with trastuzumab/LJM716, trastuzumab/BYL719, LJM716/BYL719, or trastuzumab/LJM716/BYL719 exhibited similar rates of tumor regression after 3 weeks of treatment. Thirty weeks after treatment discontinuation, 14% of mice were treated with trastuzumab/LJM716/BYL719, whereas &amp;gt;80% in all other treatment groups were sacrificed due to a recurrent large tumor burden (P = 0.0066). These data suggest that dual blockade of the HER2 signaling network with an HER3 antibody that inhibits HER2-HER3 dimers in combination with a p110α-specific inhibitor in the absence of a direct HER2 antagonist is an effective treatment approach against HER2-overexpressing cancers. Cancer Res; 73(19); 6013–23. ©2013 AACR.