tbuckley/cabot-search huggingface dataset:
Serum Levels of Insulin Growth Factor (IGF-I) and IGF-Binding Protein Predict Risk of Second Primary Tumors in Patients with Head and Neck Cancer
Authors: Xifeng Wu, Hua Zhao, Kim-Anh Do, Marcella M. Johnson, Qiong Dong, Waun Ki Hong, Margaret R. Spitz
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Second primary tumors (SPTs) are a hallmark of head and neck squamous cell carcinomas (HNSCCs). Serum levels of insulin growth factors (IGFs) and their binding proteins (IGFBPs) have been associated with subsequent development of several epithelial cancers in prospective studies. Experimental Design: To examine the role of IGFs in SPT development, we conducted a nested case–control study within a randomized, placebo-controlled chemoprevention trial in patients with early-stage HNSCC. We compared prediagnostic serum IGF-I and IGFBP-3 levels in 80 patients who subsequently developed SPTs and 173 controls (patients without SPTs) matched to the cases on age (±5 years), sex, ethnicity, year of randomization, and length of follow-up. Results: The cases exhibited significantly higher levels of IGF-I and IGFBP-3 than did the controls (P = 0.001 and 0.019, respectively). Elevated IGF-I levels were associated with a 3.66-fold significantly increased risk of SPT. Lower and higher IGFBP-3 levels were associated with a 2.22- and 7.12-fold significant increased risk, respectively. The median SPT-free time was significantly shorter in patients with higher IGF-I levels than in patients with lower IGF-I levels (P &amp;lt; 0.0001). A similar trend was observed for IGFBP-3 (P = 0.002). Moreover, in the Cox proportional hazards model, higher IGF-I levels were significantly associated with increased risk of SPT with a hazard ratio of 2.78. Patients with the lower and higher IGFBP-3 levels also exhibited significantly increased risks with hazard ratios of 1.65 and 2.17, respectively. Conclusions: This is the first study demonstrating that higher IGF-I levels, and lower and higher IGFBP-3 levels are risk factors for SPT development. Thus, measuring serum IGF-I and IGFBP-3 levels may be useful markers in assessing the risk of second tumors in patients successfully treated for their index cancer.
Turning the tide: national policy approaches to increasing physical activity in seven European countries
Authors: Fiona Bull, Karen Milton, Sonja Kahlmeier, Alberto Arlotti, Andrea Backović Juričan, Olov Belander, Brian Martin, Eva Martin-Diener, Ana Marques, Jorge Mota, Tommi Vasankari, Anita Vlasveld
Journal: British Journal of Sports Medicine (2014)

Physical inactivity is one of the four leading behavioural risk factors for non-communicable disease (NCD). Like tobacco control, increasing levels of health-enhancing physical activity (HEPA) will require a national policy framework providing direction and a clear set of actions. Despite frequent calls, there has been insufficient progress on policy development in the majority of countries around the world. This study sought and summarised national HEPA policy in seven European countries (Finland, Italy, the Netherlands, Norway, Portugal, Slovenia and Switzerland).Data collection used a policy audit tool (PAT), a 27-item instrument structured into four sections.All countries reported some legislation or policy across the sectors of education, sport and health. Only some countries reported supportive policy in the transport and environment sectors. Five countries reported a stand-alone HEPA policy and six countries reported national recommendations. HEPA prevalence targets varied in magnitude and specificity and the presence of other relevant goals from different sectors highlighted the opportunity for joint action. Evaluation and the use of scientific evidence were endorsed but described as weak in practice. Only two countries reported a national multisector coordinating committee and most countries reported challenges with partnerships on different levels of policy implementation.Bringing together the key components for success within a national HEPA policy framework is not simple. This in-depth policy audit and country comparison highlighted similarities and differences and revealed new opportunities for consideration by other countries. These examples can inform countries within and beyond Europe and guide the development of national HEPA policy within the NCD prevention agenda.
Antibodies Reactive to Non-HLA Antigens in Transplant Glomerulopathy
Authors: Rajani Dinavahi, Ajish George, Anne Tretin, Enver Akalin, Scott Ames, Jonathan S. Bromberg, Graciela DeBoccardo, Nicholas DiPaola, Susan M. Lerner, Anita Mehrotra, Barbara T. Murphy, Tibor Nadasdy, Estela Paz-Artal, Daniel R. Salomon, Bernd Schröppel, Vinita Sehgal, Ravi Sachidanandam, Peter S. Heeger
Journal: Journal of the American Society of Nephrology (2011)

Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidney-expressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre- and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.
Development and validation of the Capacity of Daily Living during the Morning questionnaire and the Global Chest Symptoms Questionnaire in COPD
Authors: M.R. Partridge, M. Miravitlles, E. Ståhl, N. Karlsson, K. Svensson, T. Welte
Journal: European Respiratory Journal (2009)

This report concerns the development and validation of two patient-reported outcomes questionnaires developed to assess chronic obstructive pulmonary disease (COPD) patients’ ability to perform morning activities and to evaluate their morning symptoms. Based on interviews with COPD patients, the Capacity of Daily Living during the Morning (CDLM) questionnaire and the Global Chest Symptoms Questionnaire (GCSQ) were developed, linguistically validated and incorporated into two multicentre, randomised trials involving a total of 1,100 COPD patients; those trials were registered at ClinicalTrials.gov ( NCT00496470 and NCT00542880 ) . Data from these trials were used to determine the reliability, validity and responsiveness of the questionnaires and to derive estimates of minimal important differences (MIDs). Both questionnaires displayed good-to-high reliability (Cronbach’s α 0.75–0.93). Analysis of convergent validity showed that CDLM and GCSQ scores correlated significantly (p&lt;0.001) with symptoms, health-related quality of life (HRQoL) and use of rescue medication. In both trials, CDLM and GCSQ scores discriminated between patients with different levels of HRQoL, as assessed by the St George's Respiratory Questionnaire for COPD patients (SGRQ-C), but not with disease severity, as assessed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. A significant improvement in CDLM and GCSQ scores occurred in response to treatment. Estimations of MID scores, corresponding to an SGRQ-C MID of 4, were 0.20 for the CDLM questionnaire and 0.15 for the GCSQ. Both the CDLM questionnaire and the GCSQ are easy-to-use, reliable, responsive, self-administered questionnaires that report on patients' symptoms and ability to perform morning activities.
Diabetic Cardiomyopathy and Subclinical Cardiovascular Disease
Authors: Alain G. Bertoni, David C. Goff, Ralph B. D’Agostino, Kiang Liu, W. Gregory Hundley, Joao A. Lima, Joseph F. Polak, Mohammed F. Saad, Moyses Szklo, Russell P. Tracy, David S. Siscovick
Journal: Diabetes Care (2006)

OBJECTIVE—Studies have demonstrated increased left ventricular mass (LVM) and diastolic dysfunction among diabetic patients without clinical cardiovascular disease (CVD), but few have assessed the potential contribution of subclinical CVD to ventricular abnormalities in diabetes. We examined whether diabetic cardiomyopathy is associated with subclinical atherosclerosis and if abnormalities are found with impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS—LVM, end-diastolic volume (EDV), and stroke volume were measured by magnetic resonance imaging (MRI), and atherosclerosis was assessed by coronary artery calcium and carotid intima-media wall thickness in 4,991 participants in the Multi-Ethnic Study of Atherosclerosis, a cohort study of adults aged 45–84 without prior CVD. Multivariable linear regression was used to analyze the association between MRI measures and glucose status. RESULTS—Increased LVM was observed in white, black, and Hispanic participants with diabetes but not among Chinese participants. After adjustment for weight, height, CVD risk factors, and subclinical atherosclerosis, ethnicity-specific differences in ventricular parameters were present. Among whites and Chinese with diabetes, LVM was similar to that in normal subjects; EDV and stroke volume were reduced. In blacks with diabetes, EDV and stroke volume were reduced, and LVM was increased (+5.6 g, P &amp;lt; 0.05). Among Hispanics with diabetes, EDV and stroke volume were similar to normal, but LVM was increased (+5.5 g, P &amp;lt; 0.05). After adjustment, IFG was associated with a decrease in EDV and stroke volume in whites and blacks only; however, no significant differences in LVM were observed. CONCLUSIONS—Ethnicity-specific differences in LVM, EDV, and stroke volume are associated with abnormal glucose metabolism and are independent of subclinical CVD.
Apixaban in Patients with Atrial Fibrillation
Authors: Stuart J. Connolly, John Eikelboom, Campbell Joyner, Hans-Christoph Diener, Robert Hart, Sergey Golitsyn, Greg Flaker, Alvaro Avezum, Stefan H. Hohnloser, Rafael Diaz, Mario Talajic, Jun Zhu, Prem Pais, Andrzej Budaj, Alexander Parkhomenko, Petr Jansky, Patrick Commerford, Ru San Tan, Kui-Hian Sim, Basil S. Lewis, Walter Van Mieghem, Gregory Y.H. Lip, Jae Hyung Kim, Fernando Lanas-Zanetti, Antonio Gonzalez-Hermosillo, Antonio L. Dans, Muhammad Munawar, Martin O'Donnell, John Lawrence, Gayle Lewis, Rizwan Afzal, Salim Yusuf
Journal: New England Journal of Medicine (2011)

Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation. However, many patients are not suitable candidates for or are unwilling to receive vitamin K antagonist therapy, and these patients have a high risk of stroke. Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients.In a double-blind study, we randomly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban (at a dose of 5 mg twice daily) or aspirin (81 to 324 mg per day), to determine whether apixaban was superior. The mean follow up period was 1.1 years. The primary outcome was the occurrence of stroke or systemic embolism.Before enrollment, 40% of the patients had used a vitamin K antagonist. The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban. There were 51 primary outcome events (1.6% per year) among patients assigned to apixaban and 113 (3.7% per year) among those assigned to aspirin (hazard ratio with apixaban, 0.45; 95% confidence interval [CI], 0.32 to 0.62; P<0.001). The rates of death were 3.5% per year in the apixaban group and 4.4% per year in the aspirin group (hazard ratio, 0.79; 95% CI, 0.62 to 1.02; P=0.07). There were 44 cases of major bleeding (1.4% per year) in the apixaban group and 39 (1.2% per year) in the aspirin group (hazard ratio with apixaban, 1.13; 95% CI, 0.74 to 1.75; P=0.57); there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin. The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin (12.6% per year vs. 15.9% per year, P<0.001). The treatment effects were consistent among important subgroups.In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable, apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage. (Funded by Bristol-Myers Squibb and Pfizer; ClinicalTrials.gov number, NCT00496769.).
Advances in our understanding of the pathology of chronic intestinal pseudo-obstruction
Authors: R De Giorgio
Journal: Gut (2004)

Chronic intestinal pseudo-obstruction (CIP) represents a particularly difficult clinical challenge. It is a rare and highly morbid syndrome characterised by impaired gastrointestinal propulsion together with symptoms and signs of bowel obstruction in the absence of any lesions occluding the gut lumen. CIP can be classified as either “secondary” to a wide array of recognised pathological conditions or “idiopathic” (CIIP). This review will focus on CIIP, and specifically on the underlying pathological abnormalities. Combined clinical and histopathological studies are needed to highlight new perspectives in the understanding and management of chronic intestinal pseudo-obstruction.
Testing the NKT cell hypothesis of human IDDM pathogenesis
Authors: Peter T. Lee, Amy Putnam, Kamel Benlagha, Luc Teyton, Peter A. Gottlieb, Albert Bendelac
Journal: Journal of Clinical Investigation (2002)

Defects in IL-4–producing CD1d-autoreactive NKT cells have been implicated in numerous Th1-mediated autoimmune diseases, including diabetes, multiple sclerosis, rheumatoid arthritis, lupus, and systemic sclerosis. Particular attention has been focused on autoimmune insulin-dependent diabetes mellitus (IDDM) because nonobese diabetic (NOD) mice and humans with IDDM are both reported to express severe deficiencies in the frequency and Th2 functions of NKT cells. Furthermore, experimental manipulations of the NKT defect in the NOD mouse induced corresponding changes in disease. Taken together, these converging studies suggested a general role of NKT cells in natural protection against destructive autoimmunity. However, in previous reports the identification of NKT cells was based on indirect methods. We have now devised a direct, highly specific CD1d tetramer–based methodology to test whether humans with IDDM have associated NKT cell defects. Surprisingly, although we find marked and stable differences in NKT cells between individuals, our study of IDDM patients and healthy controls, including discordant twin pairs, demonstrates that NKT cell frequency and IL-4 production are conserved during the course of IDDM. These results contradict previous conclusions and refute the hypothesis that NKT cell defects underlie most autoimmune diseases.
Disruption of Type 5 Adenylyl Cyclase Enhances Desensitization of Cyclic Adenosine Monophosphate Signal and Increases Akt Signal With Chronic Catecholamine Stress
Authors: Satoshi Okumura, Dorothy E. Vatner, Reiko Kurotani, Yunzhe Bai, Shumin Gao, Zengrong Yuan, Kousaku Iwatsubo, Coskun Ulucan, Jun-ichi Kawabe, Kaushik Ghosh, Stephen F. Vatner, Yoshihiro Ishikawa
Journal: Circulation (2007)

Desensitization of the cyclic adenosine monophosphate signal protects cardiac myocytes against catecholamine stress, thus preventing the development of apoptosis. Molecular mechanisms of desensitization have been well studied at the level of adrenergic receptors but less so at the level of the effector enzyme, adenylyl cyclase (AC).When the effects of long-term (1 to 2 weeks) isoproterenol infusion were compared between type 5 AC-null mice (AC5KO) and wild-type controls, we found that the subsequent responses of left ventricular ejection fraction to sudden intravenous isoproterenol challenge were reduced in AC5KO compared with wild-type mice (ie, physiological desensitization was more effective in AC5KO), consistent with enhanced downregulation of AC catalytic activity in AC5KO. One mechanism for the less effective desensitization in wild-type mice was paradoxical upregulation of type 5 AC protein expression. The number of apoptotic myocytes was similar at baseline but was significantly less in AC5KO after infusion. This was accompanied by a 4-fold greater increase in Bcl-2 and a 3-fold greater increase in phospho-Akt in AC5KO. The latter is most likely mediated by increased membrane localization of phosphoinositide-dependent protein kinase 1, which is known to be inhibited by the cyclic adenosine monophosphate signal.The absence of type 5 AC results in more effective desensitization after long-term catecholamine stress and protects against the development of myocyte apoptosis and deterioration of cardiac function, potentially elucidating a novel approach to the therapy of heart failure.
Quality of life and patients' satisfaction in chronic urticaria and respiratory allergy
Authors: I. Baiardini, A. Giardini, M. Pasquali, P. Dignetti, L. Guerra, C. Specchia, F. Braido, G. Majani, G. W. Canonica
Journal: Allergy (2003)

Background: Few articles are available about chronic urticaria (CU) impact on patients’ quality of life (QoL). The aim of our study was to evaluate QoL in CU patients both focusing on health status and subjective satisfaction. We adopted two generic tools: SF‐36 (an health status questionnaire) and SAT‐P (a satisfaction profile). Methods: Twenty‐one untreated patients (five males, 16 females; aged 46.3 ± 12.4) affected by CU, were enrolled. SF‐36 and SAT‐P scores of CU patients were compared with scores of a group of 27 patients with respiratory allergy. Published reference values of 608 and 241 Italian healthy subjects were used as controls, respectively, for SF‐36 and SAT‐P. Results: Patients with CU compared with allergic patients referred significantly lower scores in physical functioning ( P = 0.046), role physical ( P = 0.01), bodily pain ( P = 0.0001), general health ( P = 0.0043) and role emotional ( P = 0.04), and compared with reference sample reported lower scores in all SF‐36 domains ( P &lt; 0.0001). SAT‐P scores of CU patients compared with patients with respiratory allergy and with reference sample were significantly lower in many aspects of daily life. Conclusions: These results show a significant impact on health status and on subjective satisfaction in patients with CU: the symptoms affect everyday life, limiting and impairing physical and emotional functioning, and acts as an indirect burden on life satisfaction.
The Integrated Skin Exam film: An educational intervention to promote early detection of melanoma by medical students
Authors: Amit Garg, Joyce Wang, Shalini B. Reddy, Jennifer Powers, Reza Jacob, Michael Powers, Katie Biello, Rachael Cayce, Stephanie Savory, Leah Belazarian, Erik Domingues, Adam Korzenko, Lindsay Wilson, Jane M. Grant-Kels, Paul George, Leslie Robinson-Bostom, Shannon C. Trotter, Alan C. Geller
Journal: Journal of the American Academy of Dermatology (2013)
Myeloma-Specific Multiple Peptides Able to Generate Cytotoxic T Lymphocytes: A Potential Therapeutic Application in Multiple Myeloma and Other Plasma Cell Disorders
Authors: Jooeun Bae, Robert Smith, John Daley, Naoya Mimura, Yu-Tzu Tai, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Clinical Cancer Research (2012)

The efficacy of peptide vaccines may be enhanced by stimulating immune cells with multiple peptides derived from distinct tumor-associated antigens. We have evaluated the heteroclitic XBP1-US(184-192) (YISPWILAV), heteroclitic XBP1-SP(367-375) (YLFPQLISV), native CD138(260-268) (GLVGLIFAV), and native CS1(239-247) (SLFVLGLFL) peptides, which have strong HLA-A2 affinity and immunogenicity in combination, for their ability to elicit multiple myeloma antigen-specific responses.Multipeptide-specific cytotoxic T lymphocytes (MP-CTL) were generated by the stimulation of CD3(+) T lymphocytes from HLA-A2(+) individuals with either autologous mature dendritic cells or T2 cells pulsed with a cocktail of these four peptides.The peptide cocktail did not compromise tumor antigen-specific activity of CTLs. MP-CTLs displayed increased total, effector memory (CCR7(-)CD45RO(+)), and activated (CD69(+)) CD3(+)CD8(+) T lymphocytes. In addition, MP-CTL showed IFN-γ production, cell proliferation, and cytotoxicity against HLA-A2(+) multiple myeloma cells, including cells of HLA-A2(+) patients with multiple myeloma. Importantly, MP-CTLs showed specific responses in functional assays to each relevant peptide but not to an irrelevant HLA-A2-specific CMV pp65 (NLVPMVATV) peptide.These results highlight the potential therapeutic application of vaccination with a cocktail of HLA-A2-specific peptides to induce CTLs with a broad spectrum of immune responses against multiple myeloma antigens.
Home non-invasive ventilation (HNIV) improves survival in hypercapnic patients with cystic fibrosis
Authors: Sergey Avdeev, Gulsara Baimakanova, Stanislav Krasovsky, Victor Samoilenko, Elena Amelina, Alexander Chuchalin
Journal: European Respiratory Journal (2012)

Background: The clinical benefits of home non-invasive positive pressure ventilation (HNIV) have not been well established in adult patients with cystic fibrosis (CF).  Objective: The purpose of this matched case-control study was to compare the effects of HNIV and long-term oxygen therapy (LTOT) on survival of adult CF patients with chronic hypercapnic respiratory failure (CHRF).  Methods: Twelve patients receiving HNIV were matched with 12 patients receiving LTOT regarding age, FEV1, PaCO2 and BMI.  Results: There were no differences between groups of patients in demographics, clinical and functional characteristics (HNIV patients: 24.9±4.8 years, BMI 16.1±3.3 kg/m2, FEV1 15.3±3.4%, PaCO2 59.8±7.7 mmHg; and LTOT patients: 23.9±4.6 years, BMI 15.8±4.2 kg/m2, FEV1 16.1±4.4%, PaCO2 61.4±7.9 mm Hg). HNIV settings were: ST mode, IPAP 20.1±4.2 cm H2O, EPAP 4.6±0.7 cm H2O (nasal mask – 4, oronasal mask – 8). Compared with LTOT, HNIV significantly reduced breathing rate (p=0.036), PaCO2 (p=0.038) and number of exacerbations (p=0.028). Survival was significantly better in HNIV group in comparison with LTOT group (survival time 12.5 [95%CI 0.6-16.4] months vs 6.0 [95%CI 0.7-7.3] months; log-rank test, p=0.024).  Conclusions: The survival of adult CF patients receiving HNIV was better than that of patients treated with LTOT alone. We suggest HNIV is a first-line treatment for adult CF patients with CHRF.
Limited humoral and cellular responses to Q fever vaccination in older adults with risk factors for chronic Q fever
Authors: Teske Schoffelen, Tineke Herremans, Tom Sprong, Marrigje Nabuurs-Franssen, Peter C. Wever, Leo A.B. Joosten, Mihai G. Netea, Jos W.M. van der Meer, Henk A. Bijlmer, Marcel van Deuren
Journal: Journal of Infection (2013)