tbuckley/cabot-search huggingface dataset:
Cancer and Leukemia Group B Clinical Research Associates Committee
Authors: Kandie C. Price, Barbara K. Barrett, Jean M. Roark
Journal: Clinical Cancer Research (2006)

Abstract The Cancer and Leukemia Group B is dedicated to developing and implementing training programs that will enhance the skills and abilities of Clinical Research Associates (CRA) involved in all aspects of data collection and research. Training programs not only improve overall knowledge and professionalism but also improve the integrity of study data. The CRA roles and responsibilities include the following: collect, analyze, and monitor data; collaborate with other members of the health care team; insure regulatory mandates are followed; manage the care of research participants; assist in the recruitment and enrollment of human subjects; protect subjects rights by adhering to Institutional Review Board guidelines, the Code of Federal Regulations; prepare and submit timely adverse event experience reports; maintain case report forms and drug accountability records; educate other health care professionals, patients, and families regarding clinical trials; participate in research audits; and function as a team member with the research team. In addition, CRAs may also be responsible for writing reports, grant, and budget development and the development of protocols, forms, and informed consent documents.
Speech segmentation and word discovery: a computational perspective
Authors: MR Brent
Journal: Trends in Cognitive Sciences (1999)

The segmentation and word discovery problem arises because speech does not contain any reliable acoustic analog of the blank spaces between words of printed English. As a result, children must segment the utterances they hear in order to discover the sound patterns of individual words in their language. A number of computational models have been proposed to explain how children segment speech and discover words, including ten new models in the last five years. This paper reviews all proposed models and organizes them according to their fundamental segmentation strategies, their processing characteristics, and the ways in which they use memory. All proposed models are found to use one of three fundamental strategies: the utterance-boundary strategy, the predictability strategy, or the word-recognition strategy. Selected predictions of the models are explained, their performance in computer simulations is summarized, and behavioral evidence bearing on them is discussed. Finally, ideas about how these diverse models might be synthesized into one comprehensive model are offered.
The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study
Authors: Ted Cohen, Megan Murray, Kristina Wallengren, Gonzalo G. Alvarez, Elizabeth Y. Samuel, Douglas Wilson
Journal: PLoS Medicine (2010)

Background Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis. Methods and Findings We studied a representative sample of 240 adult inpatients (aged 20–45 years) dying after admission to Edendale Hospital. Limited autopsies included collection of respiratory tract secretions and tissue by needle core biopsies of lung, liver, and spleen. Specimens were examined by fluorescent microscopy for acid-fast bacilli and cultured in liquid media; cultures positive for M. tuberculosis were tested for drug susceptibility to first- and second-line antibiotics. Ninety-four percent of our study cohort was HIV seropositive and 50% of decedents had culture-positive tuberculosis at the time of death. Fifty percent of the participants were on treatment for tuberculosis at the time of death and 58% of these treated individuals remained culture positive at the time of death. Of the 50% not receiving tuberculosis treatment, 42% were culture positive. Seventeen percent of all positive cultures were resistant to both isoniazid and rifampin (i.e., multidrug resistant); 16% of patients dying during the initiation phase of their first ever course of tuberculosis treatment were infected with multidrug-resistant bacilli. Conclusions Our findings reveal the immense toll of tuberculosis among HIV-positive individuals in KwaZulu-Natal. The majority of decedents who remained culture positive despite receiving tuberculosis treatment were infected with pan-susceptible M. tuberculosis, suggesting that the diagnosis of tuberculosis was made too late to alter the fatal course of the infection. There is also a significant burden of undetected multidrug-resistant tuberculosis among HIV-coinfected individuals dying in this setting. New public health approaches that improve early diagnosis of tuberculosis and accelerate the initiation of treatment are urgently needed in this setting. Please see later in the article for the Editors' Summary
Systematic review of endometriosis pain assessment: how to choose a scale?
Authors: Nicolas Bourdel, João Alves, Gisele Pickering, Irina Ramilo, Horace Roman, Michel Canis
Journal: Human Reproduction Update (2014)

Numerous studies concerning endometriosis and pain have been reported. However, there is no consensus on the best method to evaluate pain in endometriosis and many scales have been used. Moreover, there are only a few descriptions of minimal clinically important differences after treatment (MCID) to evaluate variations in pain. In our study, we aim to identify pain scales used in endometriosis pain treatment, to address their strong and weak points and to define which would be the ideal scale to help clinicians and researchers to evaluate endometriosis-related pain.A search of the MEDLINE and EMBASE databases was carried out for publications in English, French or Portuguese from 1980 to December 2012, for the words: endometriosis, treatment, pain. Studies were selected if they studied an endometriosis treatment and a pain scale was specified. A quantitative and a qualitative analysis of each scale was performed to define strong and weak points of each scale (systematic registration number: CRD42013005336).A total of 736 publications were identified. After excluding duplications and applying inclusion criteria 258 studies remained. We found that the visual analog scale (VAS) is the most frequently used scale. Both VAS and the numerical rating scale (NRS) show a good balance between strong and weak points in comparison with others such as the Biberoglu and Behrman scale. Concerning MCID, only VAS, NRS and Brief Pain Inventory scales have reported MCID and, among these, only VAS MCID has been studied in endometriosis patients (VAS MCID = 10 mm). Adding the Clinical Global Impression score (CGI) to the pain scale allows calculation of the MCID.When using pain scales their strengths and weaknesses must be known and included in the analysis. VAS is the most frequently used pain scale and, together with NRS, seems the best adapted for endometriosis pain measurement. The use of VAS or NRS for each type of typical pain related to endometriosis (dysmenorrhea, deep dyspareunia and non-menstrual chronic pelvic pain), combined with the CGI and a quality-of-life scale will provide both clinicians and researchers with tools to evaluate treatment response.
Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study)
Authors: A. Guermazi, J. Niu, D. Hayashi, F. W. Roemer, M. Englund, T. Neogi, P. Aliabadi, C. E. McLennan, D. T. Felson
Journal: BMJ (2012)

To examine use of magnetic resonance imaging (MRI) of knees with no radiographic evidence of osteoarthritis to determine the prevalence of structural lesions associated with osteoarthritis and their relation to age, sex, and obesity.Population based observational study.Community cohort in Framingham, MA, United States (Framingham osteoarthritis study).710 people aged >50 who had no radiographic evidence of knee osteoarthritis (Kellgren-Lawrence grade 0) and who underwent MRI of the knee.Prevalence of MRI findings that are suggestive of knee osteoarthritis (osteophytes, cartilage damage, bone marrow lesions, subchondral cysts, meniscal lesions, synovitis, attrition, and ligamentous lesions) in all participants and after stratification by age, sex, body mass index (BMI), and the presence or absence of knee pain. Pain was assessed by three different questions and also by WOMAC questionnaire.Of the 710 participants, 393 (55%) were women, 660 (93%) were white, and 206 (29%) had knee pain in the past month. The mean age was 62.3 years and mean BMI was 27.9. Prevalence of "any abnormality" was 89% (631/710) overall. Osteophytes were the most common abnormality among all participants (74%, 524/710), followed by cartilage damage (69%, 492/710) and bone marrow lesions (52%, 371/710). The higher the age, the higher the prevalence of all types of abnormalities detectable by MRI. There were no significant differences in the prevalence of any of the features between BMI groups. The prevalence of at least one type of pathology ("any abnormality") was high in both painful (90-97%, depending on pain definition) and painless (86-88%) knees.MRI shows lesions in the tibiofemoral joint in most middle aged and elderly people in whom knee radiographs do not show any features of osteoarthritis, regardless of pain.
Impact of Tacrolimus and Mycophenolate Mofetil Combination on Cardiovascular Risk Profile after Kidney Transplantation
Authors: Jose María Morales, Beatriz Domínguez-Gil
Journal: Journal of the American Society of Nephrology (2006)

Cardiovascular risk factors after kidney transplantation are enhanced as a result of the chronic use of immunosuppressants. Tacrolimus with mycophenolate mofetil has become the most commonly used combination after kidney transplantation. Cardiovascular risk factors that are related to the use of this combined therapy have been analyzed in various clinical trials in comparison with other immunosuppressive therapies. This review summarizes the main results of these studies regarding arterial hypertension, lipid profile, posttransplantation diabetes, renal function, and even acute rejection rate. The aim is to characterize the cardiovascular risk profile of tacrolimus and mycophenolate mofetil association when compared with older and newer immunosuppressive associations.
The early phase of psoriatic arthritis
Authors: D. McGonagle, Z. Ash, L. Dickie, M. McDermott, S. Z. Aydin
Journal: Annals of the Rheumatic Diseases (2011)

Evaluation of the preclinical phases of the classic autoimmune diseases including rheumatoid arthritis has been facilitated by the availability of autoantibody and genetic markers that point firmly towards the early dysregulation of the adaptive immune responses. The association of psoriatic disease with the human leucocyte antigen—Cw0602 (HLA-Cw0602) gene has likewise led to the perception that autoimmunity has a pivotal role in early psoriatic arthritis (PsA). However, this HLA-Cw0602 genetic association does not appear to hold for PsA or associated nail, scalp and intergluteal skin involvement. Of note, these three sites of psoriasis are predictive of PsA evolution. For initiation of both skin and nail disease there is a link with Koebnerisation, or site-specific trauma. Nail disease is most common in the dominant hand thumbnail, pointing towards local tissue factors as disease initiators Likewise, for PsA, there is also good evidence for a history of previous joint trauma and histological studies showing microdamage in normal entheses which are typical locations where PsA frequently occurs. Furthermore, subclinical enthesopathy including osteitis is common in subjects with psoriasis but without arthritis. Collectively, these findings indicate that the classic model of adaptive immune dysregulation does not generally hold for the early stages of PsA. The way in which knowledge pertaining to tissue-specific factors in PsA, combined with the emerging data relating to monogenic disorders and animal models, points towards perturbation in the healing response and dysregulation of innate immune responses in early PsA is discussed. The way in which this model explains the clinical disconnect between skin and joint disease and the emerging human data that support it are demonstrated.
A Familial Pattern of Thyroglossal Duct Cysts
Authors: J. Scott Millikan
Journal: JAMA (1980)

CONGENITAL lesions make up about 6% of all masses found within the neck. 1 Approximately two thirds of these congenital abnormalities involve the thyroglossal duct in the form of cysts or sinuses. Despite the frequent occurrence of thyroglossal duct malformations, a familial pattern, to our knowledge, has not been described.  Report of a Case  A healthy 1-year-old girl was admitted to the Denver General Hospital with a painless, midline cervical mass over the hyoid bone. There was no history of airway or feeding problems and no symptoms of any endocrine disorder. The family history was remarkable for hypothyroidism, thyroid carcinoma, and thyroglossal duct defects (Figure).  Physical examination disclosed a 1×1-cm, nontender cervical mass located in the midline at the level of the hyoid bone. No cutaneous fistulous tract was noted.  These findings were suggestive of a thyroglossal duct cyst. Surgical excision, using the Sistrunk technique, 2 demonstrated a squamous cell-lined
Statins in the Treatment of Chronic Heart Failure: A Systematic Review
Authors: Pim van der Harst, Adriaan A Voors, Wiek H van Gilst, Michael Böhm, Dirk J van Veldhuisen
Journal: PLoS Medicine (2006)

Background The efficacy of statin therapy in patients with established chronic heart failure (CHF) is a subject of much debate. Methods and Findings We conducted three systematic literature searches to assess the evidence supporting the prescription of statins in CHF. First, we investigated the participation of CHF patients in randomized placebo-controlled clinical trials designed to evaluate the efficacy of statins in reducing major cardiovascular events and mortality. Second, we assessed the association between serum cholesterol and outcome in CHF. Finally, we evaluated the ability of statin treatment to modify surrogate endpoint parameters in CHF. Using validated search strategies, we systematically searched PubMed for our three queries. In addition, we searched the reference lists from eligible studies, used the "see related articles" feature for key publications in PubMed, consulted the Cochrane Library, and searched the ISI Web of Knowledge for papers citing key publications. Search 1 resulted in the retrieval of 47 placebo-controlled clinical statin trials involving more than 100,000 patients. CHF patients had, however, been systematically excluded from these trials. Search 2 resulted in the retrieval of eight studies assessing the relationship between cholesterol levels and outcome in CHF patients. Lower serum cholesterol was consistently associated with increased mortality. Search 3 resulted in the retrieval of 18 studies on the efficacy of statin treatment in CHF. On the whole, these studies reported favorable outcomes for almost all surrogate endpoints. Conclusions Since CHF patients have been systematically excluded from randomized, controlled clinical cholesterol-lowering trials, the effect of statin therapy in these patients remains to be established. Currently, two large, randomized, placebo-controlled statin trials are under way to evaluate the efficacy of statin treatment in terms of reducing clinical endpoints in CHF patients in particular.
Toward Fulfilling the Promise of Molecular Medicine in Fragile X Syndrome
Authors: Dilja D. Krueger, Mark F. Bear
Journal: Annual Review of Medicine (2010)

Fragile X syndrome (FXS) is the most common inherited form of mental retardation and a leading known cause of autism. It is caused by loss of expression of the fragile X mental retardation protein (FMRP), an RNA-binding protein that negatively regulates protein synthesis. In neurons, multiple lines of evidence suggest that protein synthesis at synapses is triggered by activation of group 1 metabotropic glutamate receptors (Gp1 mGluRs) and that many functional consequences of activating these receptors are altered in the absence of FMRP. These observations have led to the theory that exaggerated protein synthesis downstream of Gp1 mGluRs is a core pathogenic mechanism in FXS. This excess can be corrected by reducing signaling by Gp1 mGluRs, and numerous studies have shown that inhibition of mGluR5, in particular, can ameliorate multiple mutant phenotypes in animal models of FXS. Clinical trials based on this therapeutic strategy are currently under way. FXS is therefore poised to be the first neurobehavioral disorder in which corrective treatments have been developed from the bottom up: from gene identification to pathophysiology in animals to novel therapeutics in humans. The insights gained from FXS and other autism-related single-gene disorders may also assist in identifying molecular mechanisms and potential treatment approaches for idiopathic autism.
Pharmacogenetic Assessment of Toxicity and Outcome After Platinum Plus Taxane Chemotherapy in Ovarian Cancer: The Scottish Randomised Trial in Ovarian Cancer
Authors: Sharon Marsh, Jim Paul, Cristi R. King, Gillian Gifford, Howard L. McLeod, Robert Brown
Journal: Journal of Clinical Oncology (2007)

Purpose Standard therapy for advanced ovarian cancer consists of a platinum agent in combination with a taxane, which has a 5-year survival rate of approximately 45%. The large individual variability for ovarian cancer patients in both outcome and toxicity risk from chemotherapy makes the identification of pharmacogenetic markers that can be used to screen patients before therapy selection an attractive prospect. Patients and Methods We assessed 27 selected polymorphisms based on previously described associations or putative functional effects in 16 key genes from pathways that may influence cellular sensitivity to taxanes (ABCB1, ABCC1, ABCC2, ABCG2, CDKN1A, CYP1B1, CYP2C8, CYP3A4, CYP3A5, MAPT, and TP53) and platinum (ABCC2, ABCG2, ERCC1, ERCC2, GSTP1, MPO, and XRCC1) using polymerase chain reaction and Pyrosequencing in 914 ovarian cancer patients from the Scottish Randomised Trial in Ovarian Cancer phase III trial who were treated at presentation with carboplatin and taxane regimens after cytoreductive surgery. Results No reproducible significant associations between genotype and outcome or toxicity were found for any of the genes analyzed. Previously reported genotype associations could not be replicated in this large study of a well-defined patient population within one specific clinical trial. Conclusion There are no clear candidates for taxane/platinum pharmacogenetic markers. This study highlights the need for validation of putative genetic markers in large, well-defined clinical sample sets.
PPARα inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia by inducing the tumor suppressor p16INK4a
Authors: Florence Gizard, Carole Amant, Olivier Barbier, Stefano Bellosta, Romain Robillard, Frédéric Percevault, Henry Sevestre, Paul Krimpenfort, Alberto Corsini, Jacques Rochette, Corine Glineur, Jean-Charles Fruchart, Gérard Torpier, Bart Staels
Journal: Journal of Clinical Investigation (2005)

Vascular SMC proliferation is a crucial event in occlusive cardiovascular diseases. PPARα is a nuclear receptor controlling lipid metabolism and inflammation, but its role in the regulation of SMC growth remains to be established. Here, we show that PPARα controls SMC cell-cycle progression at the G1/S transition by targeting the cyclin-dependent kinase inhibitor and tumor suppressor p16INK4a (p16), resulting in an inhibition of retinoblastoma protein phosphorylation. PPARα activates p16 gene transcription by both binding to a canonical PPAR-response element and interacting with the transcription factor Sp1 at specific proximal Sp1-binding sites of the p16 promoter. In a carotid arterial–injury mouse model, p16 deficiency results in an enhanced SMC proliferation underlying intimal hyperplasia. Moreover, PPARα activation inhibits SMC growth in vivo, and this effect requires p16 expression. These results identify an unexpected role for p16 in SMC cell-cycle control and demonstrate that PPARα inhibits SMC proliferation through p16. Thus, the PPARα/p16 pathway may be a potential pharmacological target for the prevention of cardiovascular occlusive complications of atherosclerosis.
A constructionist account of emotional disorders
Authors: Angélique O. J. Cramer, Kenneth S. Kendler, Denny Borsboom
Journal: Behavioral and Brain Sciences (2012)

Abstract Lindquist et al. present a strong case for a constructionist account of emotion. First, we elaborate on the ramifications that a constructionist account of emotions might have for psychiatric disorders with emotional disturbances as core elements. Second, we reflect on similarities between Lindquist et al.'s model and recent attempts at formulating psychiatric disorders as networks of causally related symptoms.
Targeting diphtheria toxin to growth factor receptors
Authors: John R. Murphy, Johanna C. vanderSpek
Journal: Seminars in Cancer Biology (1995)

Biochemical, genetic and X-ray crystallographic analysis of diphtheria toxin have demonstrated that the native toxin is composed of three structural domains that function in an ordered fashion to intoxicate a eukaryotic cell. With the knowledge that, if delivered to the cytosol, a single molecule of the catalytic domain is lethal for the cell, we have used recombinant DNA methods to genetically replace the native toxin receptor binding domain with a series of growth factors. The resulting diphtheria toxin-related cytokine fusion proteins, or fusion toxins bind to their respective receptors, are internalized by receptor-mediated endocytosis, and efficiently eliminate target cell populations by the adenosine diphosphate ribosylation of elongation factor 2. Based upon the results of preclinical studies, DAB486IL-2, DAB389IL-2 and DAB389EGF have, or are in the process of being evaluated in Phase I/II clinical trials. To date, administration of the diphtheria toxin-based fusion proteins targeted toward the high affinity IL-2 receptor have been found to be safe, well tolerated, and capable of inducing remission in refractory hematologic malignancies.