tbuckley/cabot-search huggingface dataset:
Established criteria for disease controlling drugs in ankylosing spondylitis
Authors: D D Gladman
Journal: Annals of the Rheumatic Diseases (2003)

The ASAS recommendations for the initiation of DC-ART in AS are a good start

Ankylosing spondylitis (AS) is primarily an inflammatory arthritis of the back, affecting the sacroiliac and apophysial joints.1 The age of onset is usually late teens with men being affected nine times more than women. Onset is gradual with pain and stiffness in the low back, characteristically at night or early morning.2 The natural history of AS is progression to affect the whole spine, resulting in spinal deformities. These include flattening of the lumbar lordosis, kyphosis of the thoracic spine, and hyperextension of the cervical spine, with eventual flexion contractures of the hips and knees and significant morbidity and disability. These clinical features are mirrored by the radiological changes of syndesmophytes and ankylosis of the spine as well as erosive changes, sclerosis, and eventual ankylosis of the sacroiliac joints.3

Peripheral arthritis occurs uncommonly in AS, and when it occurs, it is usually late in the course of the arthritis.4 The development of peripheral arthritis early in the course of the disease is a predictor of disease progression.5 The arthritis usually presents in the lower extremities in an asymmetric distribution. Involvement of the “axial” joints, including shoulders and hips, is more common than involvement of more distal joints. In the shoulder, there may be a unique lesion of erosion at insertion of the rotator cuff.6 In the hips, progressive flexion deformity and eventual destruction of the joint may occur. In addition, enthesitis, or inflammation at sites of tendon insertion into bone, is common, affecting primarily plantar fascia and Achilles tendon insertion. The disease is often complicated by the presence of iritis (particularly anterior uveitis), cardiac manifestations (including dilatation of the root of the aorta and conduction defects), …
Individual Physician Practice Variation in Hematopoietic Cell Transplantation
Authors: Stephanie J. Lee, Steven Joffe, Andrew S. Artz, Richard E. Champlin, Stella M. Davies, Madan Jagasia, Nancy A. Kernan, Fausto R. Loberiza, Robert J. Soiffer, Mary Eapen
Journal: Journal of Clinical Oncology (2008)

Previous studies have evaluated practice variation in hematopoietic cell transplantation (HCT) among transplant centers and countries. There are no studies investigating individual physician practice variation in HCT.An international Internet-based survey of transplant physicians collected data on medical decisions made by adult and pediatric HCT physicians. Multivariable analyses identified practitioner and transplant center characteristics predictive of medical decision making.Analysis of 526 assessable respondents showed a wide variation in management approaches to specific clinical scenarios. Pediatric and adult transplant physicians differed significantly in their management strategies for chronic myeloid leukemia, acute and chronic graft-versus-host disease, and choice of graft source for patients with aplastic anemia. Among adult transplant physicians, there was little agreement on the patient factors favoring reduced intensity conditioning or myeloablative conditioning.These results emphasize the heterogeneity of worldwide transplant practices. Local preferences or biases likely result in similar patients being offered different transplant and treatment procedures. The degree of practice variation also highlights the need for clinical trials to clarify areas of controversy. Where clinical trials are not feasible, data from observational studies may be the best available evidence to guide practice.
Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival
Authors: Shaosong Zhang, Jie Ren, Cindy E. Zhang, Ilya Treskov, Yibin Wang, Anthony J. Muslin
Journal: Circulation Research (2003)

14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) activation. DN-14-3-3 mice are unable to compensate for pressure overload, which results in increased mortality, dilated cardiomyopathy, and cardiac myocyte apoptosis. To evaluate the relative role of p38 MAPK activity in the DN-14-3-3 phenotype, we inhibited cardiac p38 MAPK activity by pharmacological and genetic methods. Intraperitoneal injection of SB202190, an inhibitor of p38alpha and p38beta MAPK activity, markedly increased the ability of DN-14-3-3 mice to compensate for pressure overload, with decreased mortality. DN-14-3-3 mice were bred with transgenic mice in which dominant-negative p38alpha (DN-p38alpha) or dominant-negative p38beta (DN-p38beta) MAPK expression was targeted to the heart. Compound transgenic DN-14-3-3/DN-p38beta mice, and to a lesser extent compound transgenic DN-14-3-3/DN-p38alpha mice, exhibited reduced mortality and cardiac myocyte apoptosis in response to pressure overload, demonstrating that DN-14-3-3 promotes cardiac apoptosis due to stimulation of p38 MAPK activity.
Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity
Authors: M. A. Gebska, B. K. Stevenson, A. R. Hemnes, T. J. Bivalacqua, A. Haile, G. G. Hesketh, C. I. Murray, A. L. Zaiman, M. K. Halushka, N. Krongkaew, T. D. Strong, C. A. Cooke, H. El-Haddad, R. M. Tuder, D. E. Berkowitz, H. C. Champion
Journal: Cardiovascular Research (2011)

It has been well demonstrated that phosphodiesterase-5A (PDE5A) is expressed in smooth muscle cells and plays an important role in regulation of vascular tone. The role of endothelial PDE5A, however, has not been yet characterized. The present study was undertaken to determine the presence, localization, and potential physiologic significance of PDE5A within vascular endothelial cells. We demonstrate primary location of human, mouse, and bovine endothelial PDE5A at or near caveolae. We found that the spatial localization of PDE5A at the level of caveolin-rich lipid rafts allows for a feedback loop between endothelial PDE5A and nitric oxide synthase (NOS3). Treatment of human endothelium with PDE5A inhibitors resulted in a significant increase in NOS3 activity, whereas overexpression of PDE5A using an adenoviral vector, both in vivo and in cell culture, resulted in decreased NOS3 activity and endothelium-dependent vasodilation. The molecular mechanism responsible for these interactions is primarily regulated by cGMP-dependent second messenger. PDE5A overexpression also resulted in a significant decrease in protein kinase 1 (PKG1) activity. Overexpression of PKG1 rapidly activated NOS3, whereas silencing of the PKG1 gene with siRNA inhibited both NOS3 phosphorylation (S1179) and activity, indicating a novel role for PKG1 in direct regulation of NOS3. Our data collectively suggest another target for PDE5A inhibition in endothelial dysfunction and provide another physiologic significance for PDE5A in the modulation of endothelial-dependent flow-mediated vasodilation. Using both in vitro and in vivo models, as well as human data, we show that inhibition of endothelial PDE5A improves endothelial function.
Anti-VEGF Treatment–Resistant Pancreatic Cancers Secrete Proinflammatory Factors That Contribute to Malignant Progression by Inducing an EMT Cell Phenotype
Authors: Carmine Carbone, Tania Moccia, Cihui Zhu, Genni Paradiso, Alfredo Budillon, Paul J. Chiao, James L. Abbruzzese, Davide Melisi
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The resistance of tumors to antiangiogenic therapies is becoming increasingly relevant. There are currently no validated predictive biomarkers for selecting which cancer patients will benefit from antiangiogenic therapy. Also lacking are resistance biomarkers that can identify which escape pathways should be targeted after tumors develop resistance to VEGF treatment. Recent studies showed that anti-VEGF treatment can make tumor cells more aggressive and metastatic. However, the mechanisms and mediators of this are unidentified. Therefore, we aimed this study at directly identifying the tumor cell–initiated mechanisms responsible for the resistance of pancreatic cancer to anti-VEGF treatment. Experimental Design: We established and validated two murine models of human pancreatic cancer resistant to the VEGF-specific antibody bevacizumab in vivo. We used a genome-wide analysis to directly identify which tumor-secreted factors were overexpressed by pancreatic cancer cells that were resistant to anti-VEGF treatment. Results: Rather than direct proangiogenic factors, we identified several proinflammatory factors that were expressed at higher levels in cells resistant to anti-VEGF treatment than in treatment-sensitive control cells. These proinflammatory factors acted in a paracrine manner to stimulate the recruitment of CD11b+ proangiogenic myeloid cells. Also, we found that secreted factors overexpressed by anti-VEGF treatment-resistant pancreatic cancer cells acted in an autocrine manner to induce epithelial-to-mesenchymal transition (EMT) and were thus responsible for increased aggressiveness of bevacizumab-resistant pancreatic tumors. Conclusions: Our results identified proinflammatory factors and EMT markers as potential biomarkers for selecting patients with pancreatic cancer for antiangiogenic therapy. Clin Cancer Res; 17(17); 5822–32. ©2011 AACR.
MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines
Authors: Surender Khurana, Nitin Verma, Jonathan W. Yewdell, Anne Katrin Hilbert, Flora Castellino, Maria Lattanzi, Giuseppe Del Giudice, Rino Rappuoli, Hana Golding
Journal: Science Translational Medicine (2011)

Adjuvant use improves the quality and quantity of the immune response to pandemic influenza vaccines.
Radiation-induced meningiomas: A shadow in the success story of childhood leukemia
Authors: Joanna Banerjee, Eija Pääkkö, Marika Harila, Riitta Herva, Juho Tuominen, Antero Koivula, Marjatta Lanning, Arja Harila-Saari
Journal: Neuro-Oncology (2009)

While the prognosis of acute childhood leukemia has improved, long-term survivors are increasingly experiencing late effects of the treatment. Cranially irradiated survivors are predisposed to the development of CNS tumors. Our aim was to describe the incidence of secondary brain tumors and to define the significance of treatment-related risk factors and host characteristics in a cohort of childhood leukemia survivors. Our cohort consisted of 60 consecutive cranially irradiated adult survivors of childhood leukemia treated in Oulu University Hospital (Oulu, Finland); MRI of the brain was performed on 49. The sites of the tumors, their histology, and details of the leukemia treatment were determined. Of the 49 patients, 11 (22%) 1-8 years of age at the time of diagnosis developed meningioma later in life, while no other brain tumors were seen. In this cohort, the development of meningioma seemed to show undisputable linkage with long latency periods (mean, 25 years; range, 14-34 years) and an increasing incidence 20 years after the treatment (47%). Three patients had multiple meningiomas, two had recurrent disease, and one had an atypical meningioma. Age at the time of irradiation, gender, or cumulative doses of chemotherapeutic agents showed no significant association with the development of meningiomas. The high incidence of meningiomas in this study was associated with long follow-up periods. Although the cohort is small, it seems probable that the increasing incidence of meningioma will shadow the future of cranially irradiated leukemia survivors. Systematic brain imaging after the treatment is therefore justifiable.
Femoroacetabular impingement: prevention or intervention? The sports physician's quandary
Authors: J Cakic, J Patricios
Journal: British Journal of Sports Medicine (2014)

Femoroacetabular impingement (FAI) is a mechanical process by which the human hip fails due to pathological contact between the skeletal prominences of the acetabulum and the femur.This repetitive pathological contact occurs during normal activities of daily living as well as, more prominently, in an athletic population.This causes a microtraumatic effect and subsequently irreversible chondral damage to the acetabular as well as femoral surfaces-osteoarthritis of the hip joint. 1 Two types of impingement are identified: the first, pincer impingement, is due to an acetabular abnormality and results in over coverage of the femoral head.The second type, Cam impingement, results in femoral morphological change and alteration of the spherical portion at the head/neck junction of the femur.The majority of patients have a mixed picture, with features of Cam and pincer type of impingement. 2
Lower Airway Rhinovirus Burden and the Seasonal Risk of Asthma Exacerbation
Authors: Loren C. Denlinger, Ron L. Sorkness, Wai-Ming Lee, Michael D. Evans, Michele J. Wolff, Sameer K. Mathur, Gina M. Crisafi, Katie L. Gaworski, Tressa E. Pappas, Rose F. Vrtis, Elizabeth A. Kelly, James E. Gern, Nizar N. Jarjour
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Most asthma exacerbations are initiated by viral upper respiratory illnesses. It is unclear whether human rhinovirus (HRV)–induced exacerbations are associated with greater viral replication and neutrophilic inflammation compared with HRV colds.To evaluate viral strain and load in a prospective asthma cohort during a natural cold.Adults were enrolled at the first sign of a cold, with daily monitoring of symptoms, medication use, and peak expiratory flow rate until resolution. Serial nasal lavage and induced sputum samples were assessed for viral copy number and inflammatory cell counts.A total of 52 persons with asthma and 14 control subjects without atopy or asthma were studied for over 10 weeks per subject on average; 25 participants developed an asthma exacerbation. Detection of HRVs in the preceding 5 days was the most common attributable exposure related to exacerbation. Compared with other infections, those by a minor group A HRV were 4.4- fold more likely to cause exacerbation (P = 0.038). Overall, sputum neutrophils and the burden of rhinovirus in the lower airway were similar in control subjects without atopy and the asthma group. However, among HRV-infected participants with asthma, exacerbations were associated with greater sputum neutrophil counts (P = 0.005).HRV infection is a frequent cause of exacerbations in adults with asthma and a cold, and there may be group-specific differences in severity of these events. The absence of large differences in viral burden among groups suggests differential lower airway sensitization to the effects of neutrophilic inflammation in the patients having exacerbations.
Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27–restricted human immune response
Authors: Eva Dazert, Christoph Neumann-Haefelin, Stéphane Bressanelli, Karen Fitzmaurice, Julia Kort, Jörg Timm, Susan McKiernan, Dermot Kelleher, Norbert Gruener, John E. Tavis, Hugo R. Rosen, Jaqueline Shaw, Paul Bowness, Hubert E. Blum, Paul Klenerman, Ralf Bartenschlager, Robert Thimme
Journal: Journal of Clinical Investigation (2009)

There is an association between expression of the MHC class I molecule HLA-B27 and protection following human infection with either HIV or HCV. In both cases, protection has been linked to HLA-B27 presentation of a single immunodominant viral peptide epitope to CD8+ T cells. If HIV mutates the HLA-B27–binding anchor of this epitope to escape the protective immune response, the result is a less-fit virus that requires additional compensatory clustered mutations. Here, we sought to determine whether the immunodominant HLA-B27–restricted HCV epitope was similarly constrained by analyzing the replication competence and immunogenicity of different escape mutants. Interestingly, in most HLA-B27–positive patients chronically infected with HCV, the escape mutations spared the HLA-B27–binding anchor. Instead, the escape mutations were clustered at other sites within the epitope and had only a modest impact on replication competence. Further analysis revealed that the cluster of mutations is required for efficient escape because a combination of mutations is needed to impair T cell recognition of the epitope. Artificially introduced mutations at the HLA-B27–binding anchors were found to be either completely cross-reactive or to lead to substantial loss of fitness. These results suggest that protection by HLA-B27 in HCV infection can be explained by the requirement to accumulate a cluster of mutations within the immunodominant epitope to escape T cell recognition.
Press Releases of Science Journal Articles and Subsequent Newspaper Stories on the Same Topic
Authors: Vladimir de Semir
Journal: JAMA (1998)

Context.—Scientific journals issue press releases to disseminate scientific news about articles they publish.Objective.—To assess whether press releases about journal articles were associated with publication of subsequent newspaper stories.Design.—Retrospective content analysis of newspaper stories, journal press releases, and journal tables of contents. From December 1, 1996, to February 28, 1997, press releases and tables of contents were collected from BMJ, Nature, Science, and The Lancet, along with newspaper stories on scientific research published in The New York Times (United States), Le Figaro and Le Monde (France), El País and La Vanguardia (Spain), La Repubblica (Italy), and the International Herald Tribune.Main Outcome Measurements.—Number of newspaper stories that contained reference to articles appearing in the 4 scientific journals, number of newspaper stories that referred to journal articles described in press releases, and the order in which journal articles were mentioned in press releases.Results.—Of the 1060 newspaper stories analyzed, 142 referred to journal articles; of these, 119 (84%) referred to articles mentioned in press releases and 23 (16%) referred to journal articles not mentioned in press releases (comparison of proportions, P =.03). Articles described first or second were referenced in more newspapers than articles described later in the press release (P=.01 by χ2 analysis).Conclusions.—Journal articles described in press releases, in particular those described first or second in the press release, are associated with the subsequent publication of newspaper stories on the same topic.
An Evaluation of an Integrative Care Approach for End-Stage Renal Disease Patients
Authors: WIM VAN BIESEN, RAYMOND C. VANHOLDER, NIC VEYS, ANNEMIEKE DHONDT, NORBERT H. LAMEIRE
Journal: Journal of the American Society of Nephrology (2000)

Studies analyzing the outcome of integrative care of end-stage renal disease (ESRD) patients, whereby patients are transferred from one renal replacement modality to another according to individual needs, are scant. In this study, we analyzed 417 files of 223 hemodialysis (HD) and 194 peritoneal dialysis (PD) patients starting renal replacement therapy between 1979 and 1996, to evaluate the effect of such an approach. Analysis was done for survival of patients on their first modality, for intention-to-treat survival (counting total time on renal replacement therapy, but with exclusion of time on transplantation), and for total survival. Log rank analysis was used and correction for risk factors was performed by Cox proportional hazards regression. Intention-to-treat survival and total survival were not different between PD and HD patients (log rank, P > 0.05). Technique success was higher in HD patients compared to PD patients (log rank, P = 0.01), with a success rate after 3 yr of 61 and 48%, respectively. Thirty-five patients were transferred from HD to PD and 32 from PD to HD. Transfer of PD patients to HD was accompanied by an increase in survival compared to those remaining on PD (log rank, P = 0.001), whereas, in contrast, transfer of patients from HD to PD was not (log rank, P = 0.17). Survival of patients remaining more than 48 mo on their initial modality was lower for PD patients (log rank, P < 0.01). A matched-pair analysis between patients who started on PD and who were transferred to HD later (by definition called integrative care patients), and patients who started and remained on HD, showed a survival advantage for the integrative care patients. These results indicate that patient outcome is not jeopardized by starting patients on PD, at least if patients are transferred in a timely manner to HD when PD-related problems arise.
Import of norovirus infections in the Netherlands and Ireland following pilgrimages to Lourdes, 2008 – preliminary report
Authors: L Verhoef, E Duizer, H Vennema, J Siebenga, C Swaan, L Isken, M Koopmans, K Balay, P Pothier, P McKeown, G van Dijk, P Capdepon, G Delmas
Journal: Eurosurveillance (2008)

Between mid-September and 19 October 2008, nine clusters of norovirus infection involving around 90 primary cases and over a hundred secondary cases were identified in patients from the Netherlands, Ireland, Italy and France, linked to pilgrimage to Lourdes, France.
Relationships of active smoking to asthma and asthma severity in the EGEA study
Authors: V Siroux, I Pin, M.p Oryszczyn, N Le Moual, F Kauffmann
Journal: European Respiratory Journal (2000)

The role of smoking as potential risk factor, selection factor ("healthy smoker" effect) and modifying factor (severity) of asthma was studied in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The analysis involved 200 adult asthmatic cases recruited in chest clinics, 265 nonasthmatic controls and 586 relatives of asthmatics (147 with asthma). Asthma in childhood was not associated with a reduced take-up of smoking (odds ratio (OR)=1.06 in males and 0.98 in females), but smoker asthmatic cases quit more often than controls (OR = 2.20 (95% confidence interval (95% CI) 1.11-4.34) in males and 2.76 (1.19-6.42) in females). Adult onset asthma was unrelated to ever smoking (OR 1.07 in males and 1.02 in females). In asthmatic cases, active smoking was associated with asthma severity. Current smokers, compared to never and exsmokers, had more asthma symptoms, more frequent (&gt; or =1 attack x day(-1)) asthma attacks (OR 2.39 (95% CI 1.06-5.36)) and higher asthma severity scores. No clear pattern regarding the relationships of smoking habits with asthma was observed in first degree relatives. It is concluded that active smoking is not a risk factor for asthma in adulthood, but that smoking increases asthma severity.
Patient's device preference in study of new inhaler. Do patients find the new device user-friendly?
Authors: Tadeusz Plusa, Pawel Bijos
Journal: European Respiratory Journal (2014)

Backgrounds: Dry powder inhalers are used in the treatment of respiratory diseases. Ease use of the inhaler device means better control of the disease and it provides great benefit to the patient. The aim of the study was to gain what do asthma/COPD patients think on the new device [Spiromax]. Material and methods: It was conducted semi-quantitative market research with qualitative face to face interviews(each 60 minutes). Patients tried out the device – interviewers noted down their observations. There were 80 patients interviews in 8 European countries. Results:  The majority of patients regard the new device as being user-friendly.  80% of the patients using the current device [Symbicort Turbohaler] find the new device more intuitive. The main reason for considering new device by patients as being better than current device was: automatic priming mechanism in one step by simply opening the cover, better loading mechanism and better dose counter. Conclusions: Asthma/COPD patients find the new device [Spiromax] to be preferred device than actual inhaler and they also recognize that the new device is user-friendly.