tbuckley/cabot-search huggingface dataset:
Globalization of the Radiation Therapy Oncology Group: Implementation of a Model for Service Expansion and Public Health Improvement
Authors: Benjamin W. Corn, Isaiah D. Wexler, Mohan Suntharalingam, Moshe Inbar, Walter J. Curran
Journal: Journal of Clinical Oncology (2008)

The Radiation Therapy Oncology Group (RTOG) is part of the cooperative group network that is overseen by the National Cancer Institute (NCI). Although the NCI is a US-based group, it has empowered the cooperative groups to recruit foreign institutions to participate in collaborative clinical trials. The RTOG undertook the challenge of globalizing its efforts in 2004. This article describes the rationale for this decision and the tactics adopted by the first hospital outside of North America to enroll patients onto RTOG trials. The challenges confronted by foreign institutions seeking admission to the RTOG and the mechanism by which Tel Aviv Medical Center (TAMC) met these challenges are described. Shortly after its acceptance, TAMC emerged as one of the leading accruers of patients to RTOG studies. The public health implications of this accomplishment are discussed.
Complement Receptor 1 Gene Polymorphisms Are Associated with Idiopathic Pulmonary Fibrosis
Authors: Michele Zorzetto, Ilaria Ferrarotti, Rocco Trisolini, Luigi Lazzari Agli, Roberta Scabini, Monique Novo, Annalisa De Silvestri, Marco Patelli, Miryam Martinetti, MariaClara Cuccia, Venerino Poletti, Ernesto Pozzi, Maurizio Luisetti
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrotic disorder underlain by aberrant wound healing of repeated lung injury. Environmental triggers and genetic background are likely to act as modifiers of the fibrotic response. Erythrocyte complement receptor 1 is a membrane protein mediating the transport of immune complexes to phagocytes. Three gene polymorphisms are related to the erythrocyte surface density of complement receptor 1 molecules, which in turn are related to the rate of immune complexes' clearance. There is evidence of association between sarcoidosis and the complement receptor 1 gene. We wondered whether IPF is associated with the complement receptor 1 gene alleles coding for a reduced molecule/erythrocyte ratio. We studied 74 patients and 166 control subjects. Three polymorphic sites of the gene, A3650G exon 22, HindIII RFLP intron 27, and C5507G exon 33, were analyzed and found to be in linkage disequilibrium. The GG genotype for the C5507G exon 33 polymorphism was significantly more common in patients with IPF than in control subjects (odds ratio = 6.232, 95% confidence interval = 2.198–18.419, p = 0.00023). The significant difference was found in both sexes. These findings agree with speculations on the role of the complement receptor 1 gene in idiopathic pulmonary fibrosis.
National Survey of US Oncologists' Knowledge, Attitudes, and Practice Patterns Regarding Herb and Supplement Use by Patients With Cancer
Authors: Richard T. Lee, Andrea Barbo, Gabriel Lopez, Amal Melhem-Bertrandt, Heather Lin, Olufunmilayo I. Olopade, Farr A. Curlin
Journal: Journal of Clinical Oncology (2014)

Patients with cancer commonly use complementary and alternative medicine, including herbs and supplements (HS), during cancer treatment. This national survey explored oncologists' knowledge, attitudes, and practice patterns regarding HS use by their patients.A survey was sent by mail and e-mail to a random sample of 1,000 members of the American Society for Clinical Oncology. The questions covered several topics: communication patterns, attitudes about HS, education about HS, response to HS use among hypothetical patients with cancer, knowledge of HS adverse effects, and demographic information.Among eligible oncologists, 392 (42%) responded to the questionnaire. Most were white (75%) men (71%), with a mean age of 48 years (standard deviation, 9.8 years). On average, oncologists discussed use of HS with 41% of their patients; only 26% of discussions were initiated by the oncologist. Two of three oncologists indicated they did not have enough knowledge to answer questions from patients regarding HS, and 59% had not received any education about the topic. Physician factors associated with having initiated discussions with patients about the use of HS included female sex, higher self-reported knowledge, prior education about HS, increased knowledge about HS adverse effects and interactions, and estimating that > 40% of one's patients with cancer use HS.Fewer than one half of oncologists are initiating discussions with patients about HS use, and many indicate that lack of knowledge and education is a barrier to such discussions. Improving physician education about HS may facilitate more physician-patient communication about this important topic.
Transplantation of Mesenchymal Stem Cells Improves Cardiac Function in a Rat Model of Dilated Cardiomyopathy
Authors: Noritoshi Nagaya, Kenji Kangawa, Takefumi Itoh, Takashi Iwase, Shinsuke Murakami, Yoshinori Miyahara, Takafumi Fujii, Masaaki Uematsu, Hajime Ohgushi, Masakazu Yamagishi, Takeshi Tokudome, Hidezo Mori, Kunio Miyatake, Soichiro Kitamura
Journal: Circulation (2005)

Background— Pluripotent mesenchymal stem cells (MSCs) differentiate into a variety of cells, including cardiomyocytes and vascular endothelial cells. However, little information is available about the therapeutic potency of MSC transplantation in cases of dilated cardiomyopathy (DCM), an important cause of heart failure. Methods and Results— We investigated whether transplanted MSCs induce myogenesis and angiogenesis and improve cardiac function in a rat model of DCM. MSCs were isolated from bone marrow aspirates of isogenic adult rats and expanded ex vivo. Cultured MSCs secreted large amounts of the angiogenic, antiapoptotic, and mitogenic factors vascular endothelial growth factor, hepatocyte growth factor, adrenomedullin, and insulin-like growth factor-1. Five weeks after immunization, MSCs or vehicle was injected into the myocardium. Some engrafted MSCs were positive for the cardiac markers desmin, cardiac troponin T, and connexin-43, whereas others formed vascular structures and were positive for von Willebrand factor or smooth muscle actin. Compared with vehicle injection, MSC transplantation significantly increased capillary density and decreased the collagen volume fraction in the myocardium, resulting in decreased left ventricular end-diastolic pressure (11±1 versus 16±1 mm Hg, P &lt;0.05) and increased left ventricular maximum dP / dt (6767±323 versus 5138±280 mm Hg/s, P &lt;0.05). Conclusions— MSC transplantation improved cardiac function in a rat model of DCM, possibly through induction of myogenesis and angiogenesis, as well as by inhibition of myocardial fibrosis. The beneficial effects of MSCs might be mediated not only by their differentiation into cardiomyocytes and vascular cells but also by their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic factors.
Estimation of lung growth using computed tomography
Authors: P.A. de Jong, Y. Nakano, M.H. Lequin, P.J. Merkus, H.A. Tiddens, J.C. Hogg, H.O. Coxson
Journal: European Respiratory Journal (2003)

Anatomical studies suggest that normal lungs grow by rapid alveolar addition until about 2 yrs of age followed by a gradual increase in alveolar dimensions. The aim of this study was to examine the hypothesis that normal lung growth can be monitored by computed tomography (CT). Therefore, the gas volume per gram of lung tissue was estimated from measurements of lung density obtained from CT scans performed on children throughout the growth period. CT scans were performed on 17 males and 18 females, ranging in age from 15 days–17.6 yrs. CT-measured lung weight was correlated with predicted <i>post mortem</i> values and CT measured gas volume with predicted values of functional residual capacity. The median value for lung expansion was 1.86 mL·g<sup>−1</sup> at 15 days, decreased to 0.79 mL·g<sup>−1</sup> by 2 yrs and then increased steadily to 5.07 mL·g<sup>−1</sup> at 17 yrs. Computed tomography scans can be used to estimate lung weight, gas volume and expansion of normal lungs during the growth period. The increase in the lung expansion after the age of 2 yrs suggests progressive alveolar expansion with increasing lung volume.
Rationally Designed Pharmacogenomic Treatment Using Concurrent Capecitabine and Radiotherapy for Glioblastoma; Gene Expression Profiles Associated with Outcome
Authors: Jessica M. Grunda, John Fiveash, Cheryl A. Palmer, Alan Cantor, Hassan M. Fathallah-Shaykh, L. Burt Nabors, Martin R. Johnson
Journal: Clinical Cancer Research (2010)

Previous preclinical studies suggested that concurrent capecitabine and radiation could be an effective new treatment modality for glioblastoma (GBM). In the current study, we investigate toxicity and response to this regimen and explore associations between gene expression and patient outcome.
The role of body mass index in survival outcome for lymphoma patients: US intergroup experience
Authors: F. Hong, T.M. Habermann, L.I. Gordon, H. Hochster, R.D. Gascoyne, V.A. Morrison, R.I. Fisher, N.L. Bartlett, P.J. Stiff, B.D. Cheson, M. Crump, S.J. Horning, B.S. Kahl
Journal: Annals of Oncology (2014)
Sequence variants at the TERT-CLPTM1L locus associate with many cancer types
Authors: Thorunn Rafnar, Patrick Sulem, Simon N Stacey, Frank Geller, Julius Gudmundsson, Asgeir Sigurdsson, Margret Jakobsdottir, Hafdis Helgadottir, Steinunn Thorlacius, Katja K H Aben, Thorarinn Blöndal, Thorgeir E Thorgeirsson, Gudmar Thorleifsson, Kristleifur Kristjansson, Kristin Thorisdottir, Rafn Ragnarsson, Bardur Sigurgeirsson, Halla Skuladottir, Tomas Gudbjartsson, Helgi J Isaksson, Gudmundur V Einarsson, Kristrun R Benediktsdottir, Bjarni A Agnarsson, Karl Olafsson, Anna Salvarsdottir, Hjordis Bjarnason, Margret Asgeirsdottir, Kari T Kristinsson, Sigurborg Matthiasdottir, Steinunn G Sveinsdottir, Silvia Polidoro, Veronica Höiom, Rafael Botella-Estrada, Kari Hemminki, Peter Rudnai, D Timothy Bishop, Marcello Campagna, Eliane Kellen, Maurice P Zeegers, Petra de Verdier, Ana Ferrer, Dolores Isla, Maria Jesus Vidal, Raquel Andres, Berta Saez, Pablo Juberias, Javier Banzo, Sebastian Navarrete, Alejandro Tres, Donghui Kan, Annika Lindblom, Eugene Gurzau, Kvetoslava Koppova, Femmie de Vegt, Jack A Schalken, Henricus F M van der Heijden, Hans J Smit, René A Termeer, Egbert Oosterwijk, Onno van Hooij, Eduardo Nagore, Stefano Porru, Gunnar Steineck, Johan Hansson, Frank Buntinx, William J Catalona, Giuseppe Matullo, Paolo Vineis, Anne E Kiltie, José I Mayordomo, Rajiv Kumar, Lambertus A Kiemeney, Michael L Frigge, Thorvaldur Jonsson, Hafsteinn Saemundsson, Rosa B Barkardottir, Eirikur Jonsson, Steinn Jonsson, Jon H Olafsson, Jeffrey R Gulcher, Gisli Masson, Daniel F Gudbjartsson, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2009)
P127 Copd And The Workplace; Attitudes Of Those With And Without The Condition In A Population Based Study
Authors: D. Fishwick, L. Lewis, A. Darby, J. Waterhouse, R. Wiggans, L. Bradshaw
Journal: Thorax (2014)

<h3>Background</h3> Current estimates support 15% of the total population burden of chronic obstructive pulmonary disease (COPD) to be associated with harmful inhaled occupational exposures. Despite a now substantial body of evidence relating to causation, remarkably little is known about the consequences of these inhaled exposures at an individual level, and the attitudes of workers with and without COPD to these issues. <h3>Aim</h3> The aim of this work was to explore attitudes to workplaces, and to other aspects of the management of long-term respiratory problems, from individuals within a large population study with and without COPD. <h3>Methods</h3> The primary aim of this population-based study was to assess the contribution made by inhaled occupational exposures to the development of COPD. The study was based in Sheffield, historically an industrialised part of the UK. A sub sample of cases of self reported COPD (n = 66) and non cases of COPD (n = 224) were asked to rate their views to a set of 36 pre defined statements, each rated between “don’t agree” and “completely agree” on a five point scale. Statements included enquiry about attitudes to chronic respiratory ill health, smoking, general health issues and the influences of the workplace on health. <h3>Results</h3> 290 individuals, all 55 years old or greater, participated, 172 (59%) of whom were male. The majority of participants generally agreed or completely agreed with most statements, although various differences emerged between those with and without COPD. For example, those with self reported COPD were more likely, as anticipated, to identify this condition as a longer term health problem, but less likely to agree that workers with possible breathing problems should talk to their employer about these or undergo regular spirometry to identify these. <h3>Conclusions</h3> This study has identified a set of attitudes and beliefs from those with and without COPD relating to chronic respiratory problems at work. Knowledge of these semi-quantitative data will assist the development of better workplace interventions to reduce the burden of this condition.
Sex Differences in Amphetamine-Induced Displacement of [<sup>18</sup>F]Fallypride in Striatal and Extrastriatal Regions: A PET Study
Authors: Patrizia Riccardi, David Zald, Rui Li, Sohee Park, M. Sib Ansari, Benoit Dawant, Sharlet Anderson, Neil Woodward, Dennis Schmidt, Ronald Baldwin, Robert Kessler
Journal: American Journal of Psychiatry (2006)

Objective: The authors examined gender differences in d -amphetamine-induced displacements of [ 18 F]fallypride in the striatal and extrastriatal brain regions and the correlations of these displacements with cognition and sensation seeking. Method: Six women and seven men underwent positron emission tomography (PET) with [ 18 F]fallypride before and after an oral dose of d -amphetamine. Percent displacements were calculated using regions of interest and parametric images of dopamine 2 (D 2 ) receptor binding potential. Results: Parametric images of dopamine release suggest that the female subjects had greater dopamine release than the male subjects in the right globus pallidus and right inferior frontal gyrus. Gender differences were observed in correlations of changes in cognition and sensation seeking with regional dopamine release. Conclusion: Findings revealed a greater dopamine release in women as well as gender differences in the relationship between regional dopamine release and sensation seeking and cognition.
Ethnic minorities and their perceptions of the quality of primary care
Authors: A. Sheikh
Journal: BMJ (2009)

Greater tailoring of services to local populations and personalisation of care are needed 

Societies are becoming more culturally diverse and this trend—which is driven by a combination of political and economic forces, globalisation, and improved access to travel—is set to continue. More than two decades of research, mainly from English language speaking countries, shows that ethnic minority people tend to have poorer outcomes than the white majority population for a range of diseases.1 Research from the UK has, for example, shown that the risk of an emergency admission among South Asians with asthma is three times higher than the risk in white people, and is twice as high in black individuals.2 Similar inequalities have also been noted with respect to risk of developing diabetes, ischaemic heart disease, and stroke.3 4 5 6 In the linked study (doi:10.1136/bmj.b3450), Mead and Roland assess why patients from ethnic minorities also tend to give lower evaluations of primary health care than white patients.7 

The factors underpinning inequalities …
Does Childhood Treatment of ADHD With Stimulant Medication Affect Substance Abuse in Adulthood?
Authors: Nora D. Volkow, James M. Swanson
Journal: American Journal of Psychiatry (2008)

One of the most controversial issues in childhood psychiatry is whether the wide-spread use of stimulant medications to treat children with attention deficit hyperactivity disorder (ADHD) increases the risk of substance abuse in adulthood.Part of the rationale for this concern is that stimulant medications (methylphenidate and amphetamine) share with drugs of abuse the ability to increase dopamine concentration in the nucleus accumbens, which is the neural mechanism considered crucial for their reinforcing effects (1).Indeed, methylphenidate and amphetamine are sometimes abused in some settings (2).This misuse can produce dependence.Another reason for concern is the timing of exposure.Human epidemiological studies have shown that the earlier an individual is exposed to substances with abuse potential, such as alcohol and nicotine, the greater the risk of drug abuse and dependence in adulthood (3).However, the opposite perspective has also been proposed-that stimulant treatment of children and adolescents with ADHD may reduce the risk of later substance abuse (4).Considering that individuals with ADHD are at higher-than-normal risk for substance abuse (5), it is urgent that these two perspectives be addressed properly, yet relatively few clinical studies have done so.
Prospective, Randomized, Multinational Study of Prostatic Urethral Lift Versus Transurethral Resection of the Prostate: 12-month Results from the BPH6 Study
Authors: Jens Sønksen, Neil J. Barber, Mark J. Speakman, Richard Berges, Ulrich Wetterauer, Damien Greene, Karl-Dietrich Sievert, Christopher R. Chapple, Francesco Montorsi, Jacob M. Patterson, Lasse Fahrenkrug, Martin Schoenthaler, Christian Gratzke
Journal: European Urology (2015)

Transurethral resection of the prostate (TURP) is considered the gold standard for male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, TURP may lead to sexual dysfunction and incontinence, and has a long recovery period. Prostatic urethral lift (PUL) is a treatment option that may overcome these limitations. To compare PUL to TURP with regard to LUTS improvement, recovery, worsening of erectile and ejaculatory function, continence and safety (BPH6). Prospective, randomized, controlled trial at 10 European centers involving 80 men with BPH LUTS. PUL or TURP. The BPH6 responder endpoint assesses symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation, and safety. Noninferiority was evaluated using a one-sided lower 95% confidence limit for the difference between PUL and TURP performance. Preservation of ejaculation and quality of recovery were superior with PUL (p < 0.01). Significant symptom relief was achieved in both treatment arms. The study demonstrated not only noninferiority but also superiority of PUL over TURP on the BPH6 endpoint. Study limitations were the small sample size and the inability to blind participants to enrollment arm. Assessment of individual BPH6 elements revealed that PUL was superior to TURP with respect to quality of recovery and preservation of ejaculatory function. PUL was superior to TURP according to the novel BPH6 responder endpoint, which needs to be validated in future studies. In this study, participants who underwent prostatic urethral lift responded significantly better than those who underwent transurethral resection of the prostate as therapy for benign prostatic hyperplasia with regard to important aspects of quality of life. ClinicalTrials.gov NCT01533038.
British Thoracic Society Pleural Disease Guidelines - 2010 update
Authors: N. Maskell
Journal: Thorax (2010)

context of severe asthma.Identifying the neutrophil survival factor(s) present in this patient group is clearly an important next step and, if targetable, may form the basis of a new therapeutic approach for this difficult-to-treat patient group.While this study provides further evidence that neutrophil apoptosis may be deregulated in severe asthma, a number of key questions remain.We need to understand the dynamics of cell migration into and out of the airway wall and determine the true residency times and the relative contribution of apoptosis and, indeed, other non-apoptotic death mechanisms such as autophagy, NETosis 28 and cytolysis in granulocyte clearance.We also need to understand the signals that block apoptosis in the airway wall (yet seemingly not in the airway lumen) and to determine what drives the switch from eosinophil-to neutrophildominated inflammation.Drugs which target the removal rather than the arrival of granulocytes in tissues are now emerging, 29 and such agents may offer an important adjunct to current asthma treatments.
Structural biology of presenilin 1 complexes
Authors: Yi Li, Christopher Bohm, Roger Dodd, Fusheng Chen, Seema Qamar, Gerold Schmitt-Ulms, Paul E Fraser, Peter H St George-Hyslop
Journal: Molecular Neurodegeneration (2014)

The presenilin genes were first identified as the site of missense mutations causing early onset autosomal dominant familial Alzheimer's disease. Subsequent work has shown that the presenilin proteins are the catalytic subunits of a hetero-tetrameric complex containing APH1, nicastrin and PEN-2. This complex (variously termed presenilin complex or gamma-secretase complex) performs an unusual type of proteolysis in which the transmembrane domains of Type I proteins are cleaved within the hydrophobic compartment of the membrane. This review describes some of the molecular and structural biology of this unusual enzyme complex. The presenilin complex is a bilobed structure. The head domain contains the ectodomain of nicastrin. The base domain contains a central cavity with a lateral cleft that likely provides the route for access of the substrate to the catalytic cavity within the centre of the base domain. There are reciprocal allosteric interactions between various sites in the complex that affect its function. For instance, binding of Compound E, a peptidomimetic inhibitor to the PS1 N-terminus, induces significant conformational changes that reduces substrate binding at the initial substrate docking site, and thus inhibits substrate cleavage. However, there is a reciprocal allosteric interaction between these sites such that prior binding of the substrate to the initial docking site paradoxically increases the binding of the Compound E peptidomimetic inhibitor. Such reciprocal interactions are likely to form the basis of a gating mechanism that underlies access of substrate to the catalytic site. An increasingly detailed understanding of the structural biology of the presenilin complex is an essential step towards rational design of substrate- and/or cleavage site-specific modulators of presenilin complex function.