tbuckley/cabot-search huggingface dataset:
Toward the Cure of All Children With Cancer Through Collaborative Efforts: Pediatric Oncology As a Global Challenge
Authors: Carlos Rodriguez-Galindo, Paola Friedrich, Patricia Alcasabas, Federico Antillon, Shripad Banavali, Luis Castillo, Trijn Israels, Sima Jeha, Mhammed Harif, Michael J. Sullivan, Thuan Chong Quah, Catherine Patte, Ching-Hon Pui, Ronald Barr, Thomas Gross
Journal: Journal of Clinical Oncology (2015)

Advances in the treatment of childhood cancers have resulted in part from the development of national and international collaborative initiatives that have defined biologic determinants and generated risk-adapted therapies that maximize cure while minimizing acute and long-term effects. Currently, more than 80% of children with cancer who are treated with modern multidisciplinary treatments in developed countries are cured; however, of the approximately 160,000 children and adolescents who are diagnosed with cancer every year worldwide, 80% live in low- and middle-income countries (LMICs), where access to quality care is limited and chances of cure are low. In addition, the disease burden is not fully known because of the lack of population-based cancer registries in low-resource countries. Regional and ethnic variations in the incidence of the different childhood cancers suggest unique interactions between genetic and environmental factors that could provide opportunities for etiologic research. Regional collaborative initiatives have been developed in Central and South America and the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives integrate regional capacity building, education of health care providers, implementation of intensity-graduated treatments, and establishment of research programs that are adjusted to local capacity and local needs. Together, the existing consortia and regional networks operating in LMICs have the potential to reach out to almost 60% of all children with cancer worldwide. In summary, childhood cancer burden has been shifted toward LMICs and, for that reason, global initiatives directed at pediatric cancer care and control are needed. Regional networks aiming to build capacity while incorporating research on epidemiology, health services, and outcomes should be supported.
Nutritional Metabolomics: Progress in Addressing Complexity in Diet and Health
Authors: Dean P. Jones, Youngja Park, Thomas R. Ziegler
Journal: Annual Review of Nutrition (2012)

Nutritional metabolomics is rapidly maturing to use small-molecule chemical profiling to support integration of diet and nutrition in complex biosystems research. These developments are critical to facilitate transition of nutritional sciences from population-based to individual-based criteria for nutritional research, assessment, and management. This review addresses progress in making these approaches manageable for nutrition research. Important concept developments concerning the exposome, predictive health, and complex pathobiology serve to emphasize the central role of diet and nutrition in integrated biosystems models of health and disease. Improved analytic tools and databases for targeted and nontargeted metabolic profiling, along with bioinformatics, pathway mapping, and computational modeling, are now used for nutrition research on diet, metabolism, microbiome, and health associations. These new developments enable metabolome-wide association studies (MWAS) and provide a foundation for nutritional metabolomics, along with genomics, epigenomics, and health phenotyping, to support the integrated models required for personalized diet and nutrition forecasting.
Cutting a long story (too) short
Authors: Stefan Frisch, Douglas Saddy, Angela D. Friederici
Journal: Behavioral and Brain Sciences (2000)

Both linguistic and empirical evidence fail to support Grodzinsky's account of Broca's aphasics' comprehension problems. We address concerns regarding Grodzinsky's referring to the internal subject hypothesis, the importance of case information in thematic role assignment, the processing of passives, and the adequacy of Grodzinsky's linear strategy.
High frequency of autoantibodies in patients with primary sclerosing cholangitis that bind biliary epithelial cells and induce expression of CD44 and production of interleukin 6
Authors: B Xu, U Broome, B-G Ericzon, S Sumitran-Holgersson
Journal: Gut (2002)

Sera of patients with autoimmune liver diseases were investigated for the presence of autoantibodies binding to human biliary epithelial cells (BECs). Furthermore, their functional capacity was investigated by testing their capacity to fix complement as well as induce expression of various adhesion molecules and production of cytokines.Sera from patients with various stages of primary sclerosing cholangitis (PSC; n=30), primary biliary cirrhosis (PBC; n=29), autoimmune hepatitis (AIH; n=25), and normal controls (n=12) were investigated for the presence of antibodies that reacted with unstimulated and cytokine stimulated BECs isolated from a normal healthy liver. To demonstrate organ specificity, lung epithelial cells (LECs) were used as control cells. Antibodies were tested for their functional capacity.Compared with controls (8%), significantly higher numbers of PSC patients (63%, p=0.001), but not PBC (37%, NS) or AIH (16%, NS) patients, had anti-BEC antibodies. In 90% of PSC patients, the autoantibodies reacted only with cytokine stimulated target cells. Lower numbers of PSC (6%), PBC (10%), and AIH (0%) patients had LEC antibodies. Other significant findings were that anti-BEC antibodies were found in (i) PSC patients with either the HLA-DRB1*0301 or DR2 allele compared with those without (p=0.007); and (ii) in PBC patients with end stage disease compared with those without (p=0.018). Furthermore, anti-BEC antibodies from PSC and PBC but not AIH patients induced BECs to produce high levels of the cytokine interleukin 6. IgM and IgG fractions isolated from PSC but not PBC and AIH sera induced significantly increased expression of the cell adhesion molecule CD44. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis and western blot analysis of BEC membranes demonstrated a specific band of 40 kDa with PSC sera and 45, 42, 30, and 33 kDa bands with PBC sera, which were absent in control groups.Thus for the first time we have demonstrated the presence of functionally important autoantibodies to cell surface expressed antigens on the relevant target cells of destruction, namely BECs, in PSC and PBC. These finding have important implications for the pathogenesis of bile duct destruction in these patients.
Cardiac fatigue after prolonged exercise.
Authors: P S Douglas, M L O'Toole, W D Hiller, K Hackney, N Reichek
Journal: Circulation (1987)

To determine the effects of prolonged exercise on systolic and diastolic left ventricular function, we studied 21 athletes before, at the finish (within 11 +/- 5 min), and during recovery (28 +/- 9 hr) after the Hawaii Ironman Triathlon (2.4 mile swim, 112 mile bike, 26.2 mile run). Two-dimensionally guided M mode echocardiograms were digitized for wall thickness, cavity dimension, fractional shortening, and peak rates of cavity enlargement and wall thinning. Pulsed Doppler left ventricular inflow recordings were analyzed for peak early and late velocities and their ratio. Left ventricular diastolic dimension was reduced at race finish (5.4 +/- 0.6 to 5.1 +/- 0.6 cm) and remained reduced after 1 day of recovery (5.2 +/- 0.6 cm, p less than .05). Fractional shortening fell at race finish (39 +/- 5% to 35 +/- 5%), although systolic blood pressure was unchanged, and rose to 40 +/- 4% after recovery (p less than .05). The return to prerace shortening values after recovery occurred despite continued reduction in diastolic size. Peak circumferential shortening did not change significantly. Individual reductions in fractional shortening were correlated with increases in systolic cavity size (r = -.64, p less than .01), but not with decreases in diastolic size. The stress-shortening relationship was displaced downward at race finish, but returned toward baseline after 1 day of recovery, despite a persistent reduction in cavity size. This suggests that the decrease in shortening was due to impaired contractility as well as altered preload.(ABSTRACT TRUNCATED AT 250 WORDS)
Predicting early death in patients with traumatic bleeding: development and validation of prognostic model
Authors: P. Perel, D. Prieto-Merino, H. Shakur, T. Clayton, F. Lecky, O. Bouamra, R. Russell, M. Faulkner, E. W. Steyerberg, I. Roberts
Journal: BMJ (2012)

<b>Objective</b> To develop and validate a prognostic model for early death in patients with traumatic bleeding. <b>Design</b> Multivariable logistic regression of a large international cohort of trauma patients. <b>Setting</b> 274 hospitals in 40 high, medium, and low income countries <b>Participants</b> Prognostic model development: 20 127 trauma patients with, or at risk of, significant bleeding, within 8 hours of injury in the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) trial. External validation: 14 220 selected trauma patients from the Trauma Audit and Research Network (TARN), which included mainly patients from the UK. <b>Outcomes</b> In-hospital death within 4 weeks of injury. <b>Results</b> 3076 (15%) patients died in the CRASH-2 trial and 1765 (12%) in the TARN dataset. Glasgow coma score, age, and systolic blood pressure were the strongest predictors of mortality. Other predictors included in the final model were geographical region (low, middle, or high income country), heart rate, time since injury, and type of injury. Discrimination and calibration were satisfactory, with C statistics above 0.80 in both CRASH-2 and TARN. A simple chart was constructed to readily provide the probability of death at the point of care, and a web based calculator is available for a more detailed risk assessment (http://crash2.lshtm.ac.uk). <b>Conclusions</b> This prognostic model can be used to obtain valid predictions of mortality in patients with traumatic bleeding, assisting in triage and potentially shortening the time to diagnostic and lifesaving procedures (such as imaging, surgery, and tranexamic acid). Age is an important prognostic factor, and this is of particular relevance in high income countries with an aging trauma population.
Which threshold for ER positivity? a retrospective study based on 9639 patients
Authors: M. Yi, L. Huo, K.B. Koenig, E.A. Mittendorf, F. Meric-Bernstam, H.M. Kuerer, I. Bedrosian, A.U. Buzdar, W.F. Symmans, J.R. Crow, M. Bender, R.R. Shah, G.N. Hortobagyi, K.K. Hunt
Journal: Annals of Oncology (2014)
ΔNp63 transcriptionally regulates ATM to control p53 Serine-15 phosphorylation
Authors: Ashley L Craig, Jitka Holcakova, Lee E Finlan, Marta Nekulova, Roman Hrstka, Nuri Gueven, James DiRenzo, Graeme Smith, Ted R Hupp, Borivoj Vojtesek
Journal: Molecular Cancer (2010)

DeltaNp63alpha is an epithelial progenitor cell marker that maintains epidermal stem cell self-renewal capacity. Previous studies revealed that UV-damage induced p53 phosphorylation is confined to DeltaNp63alpha-positive cells in the basal layer of human epithelium.We now report that phosphorylation of the p53 tumour suppressor is positively regulated by DeltaNp63alpha in immortalised human keratinocytes. DeltaNp63alpha depletion by RNAi reduces steady-state ATM mRNA and protein levels, and attenuates p53 Serine-15 phosphorylation. Conversely, ectopic expression of DeltaNp63alpha in p63-null tumour cells stimulates ATM transcription and p53 Serine-15 phosphorylation. We show that ATM is a direct DeltaNp63alpha transcriptional target and that the DeltaNp63alpha response element localizes to the ATM promoter CCAAT sequence. Structure-function analysis revealed that the DeltaNp63-specific TA2 transactivation domain mediates ATM transcription in coordination with the DNA binding and SAM domains.Germline p63 point mutations are associated with a range of ectodermal developmental disorders, and targeted p63 deletion in the skin causes premature ageing. The DeltaNp63alpha-ATM-p53 damage-response pathway may therefore function in epithelial development, carcinogenesis and the ageing processes.
Short- and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes.
Authors: A Remuzzi, N Perico, C S Amuchastegui, B Malanchini, M Mazerska, C Battaglia, T Bertani, G Remuzzi
Journal: Journal of the American Society of Nephrology (1993)

The short- and long-term effects of specific angiotensin II (AII) receptor blockade on the evaluation of glomerular injury in moderately hyperglycemic diabetic rats were studied. Three groups of animals were used, a control group, a group of diabetic rats treated with insulin, and a group of insulin-treated diabetic rats receiving the AII receptor antagonist losartan in drinking water. After 4 to 6 wk of observation, diabetic rats showed higher systolic blood pressure and GFR than normal controls. Losartan treatment prevented both systolic blood pressure and GFR rise. Three other groups of rats, similarly treated for a 1-yr period, were used for renal functional and morphologic evaluation. Diabetic animals had higher urinary protein excretion and glomerulosclerosis incidence than did normal controls. Losartan significantly prevented proteinuria and glomerulosclerosis. Evaluation of the sieving properties of the glomerular membrane by Ficoll fractional clearance showed an important increase in the filtration of this marker in diabetic animals, as compared with that in controls, and almost complete prevention of this change in losartan-treated animals. Theoretical analysis of fractional clearance data with a heteroporous model of glomerular size-selectivity showed that in diabetic animals the size of membrane pores was increased uniformly, as compared with that in controls. These changes were completely prevented by the AII receptor antagonist. The results presented here strongly indicate that reduction of AII activity plays a crucial role in the preservation of glomerular structure and function and suggest that the favorable effects previously observed with angiotensin-converting enzyme inhibition in this model depend directly on the reduction of AII activity.
Distinction between arrhythmic and nonarrhythmic death after acute myocardial infarction based on heart rate variability, signal-averaged electrocardiogram, ventricular arrhythmias and left ventricular ejection fraction
Authors: Juha E.K. Hartikainen, Marek Malik, Anne Staunton, Jan Poloniecki, A. John Camm
Journal: Journal of the American College of Cardiology (1996)
FlyGEM, a full transcriptome array platform for the Drosophila community.
Authors: Rick Johnston, Bruce Wang, Rachel Nuttall, Michael Doctolero, Pamela Edwards, Jining Lü, Marina Vainer, Huibin Yue, Xinhao Wang, James Minor, Cathy Chan, Alex Lash, Thomas Goralski, Michael Parisi, Brian Oliver, Scott Eastman
Journal: Genome biology (2004)

We have constructed a DNA microarray to monitor expression of predicted genes in Drosophila. By using homotypic hybridizations, we show that the array performs reproducibly, that dye effects are minimal, and that array results agree with systematic northern blotting. The array gene list has been extensively annotated and linked-out to other databases. Incyte and the NIH have made the platform available to the community via academic microarray facilities selected by an NIH committee.
Keep PNUTS in Your Heart
Authors: Francesco S. Loffredo, James R. Pancoast, Richard T. Lee
Journal: Circulation Research (2013)

Aging is a major factor in many cardiovascular diseases. The molecular factors that regulate age-related changes in cardiac physiology and contribute to the increased cardiovascular risk in the elderly are not fully understood. A study recently published in Nature suggests a specific role for microRNAs (miRNAs) in regulating cardiac aging and function, challenging the concept that aging is an inevitable process in the heart.
Quantitative PCR Analysis for <i>Bcl-2/IgH</i> in a Phase III Study of Yttrium-90 Ibritumomab Tiuxetan As Consolidation of First Remission in Patients With Follicular Lymphoma
Authors: Lindsey Goff, Karin Summers, Sameena Iqbal, Jens Kuhlmann, Michael Kunz, Tom Louton, Anton Hagenbeek, Franck Morschhauser, Barbara Putz, Andrew Lister, Ama Rohatiner
Journal: Journal of Clinical Oncology (2009)

PURPOSE The randomized First-Line Indolent Trial (FIT) was conducted in patients with advanced follicular lymphoma (FL), to evaluate the safety and efficacy of yttrium-90 ((90)Y) ibritumomab tiuxetan given as consolidation of complete or partial remission. This study of minimal residual disease was undertaken in parallel, to determine the rate of conversion from bcl-2 polymerase chain reaction (PCR) -detectable to -undetectable status and the corresponding effect on progression-free survival (PFS). PATIENTS AND METHODS Blood samples from 414 patients ((90)Y-ibritumomab, n = 208; control, n = 206) were evaluated using real-time quantitative polymerase chain reaction (RQ-PCR); 186 were found to have the bcl-2 rearrangement and were thus eligible for inclusion in the RQ-PCR analysis. Results Overall, 90% of treated patients converted from bcl-2 PCR-detectable to -undetectable disease status, compared with 36% in the control group. Treatment significantly prolonged median PFS in patients converting to bcl-2 PCR-undetectable status (40.8 v 24.0 months in the control group; P < .01, hazard ratio [HR], 0.399). In patients who had bcl-2 PCR-detectable disease at random assignment, treatment significantly prolonged median PFS (38.4 v 8.2 months in the control group; P < .01, HR, 0.293). CONCLUSION Eradication of PCR-detectable disease occurred more frequently after treatment with (90)Y-ibritumomab tiuxetan and was associated with prolongation of PFS.
Significant Coronary Stenosis in Asymptomatic Chinese With Different Glycemic Status
Authors: Yu Xu, Yufang Bi, Mian Li, Tiange Wang, Kun Sun, Min Xu, Jieli Lu, Yi Yu, Xiaoying Li, Shenghan Lai, Weiqing Wang, Guang Ning
Journal: Diabetes Care (2013)

OBJECTIVE To evaluate coronary artery stenosis in early diabetes or prediabetes asymptomatic of myocardial ischemia in community-dwelling Chinese adults. RESEARCH DESIGN AND METHODS Age- and sex-matched participants with normal glucose regulation (NGR), prediabetes, or diabetes diagnosed within 5 years, asymptomatic of coronary artery disease (CAD), were randomly selected from a community-dwelling Chinese population aged 40–60 years. Dual-source computed tomography coronary angiography was used to evaluate the existence and extent of coronary stenosis, which was considered significant if &amp;gt;50% narrowing of vessel lumen was detected. RESULTS After excluding uninterpretable segments attributable to motion artifacts, a total of 135 participants with NGR, 132 with prediabetes, and 134 with diabetes participated in data analysis. Significant coronary stenosis was detected in 10 (7.4%), 10 (7.6%), and 22 (16.4%) individuals with NGR, prediabetes, and diabetes, respectively (P for trend = 0.029). Diabetes, rather than prediabetes, was associated with a significant 2.34-fold elevated risk [odds ratio (OR) 2.34 (95% CI 1.01–5.43); P = 0.047] of significant coronary stenosis as compared with that associated with NGR. Levels of glucose evaluation were independently and significantly associated with risks of significant coronary stenosis in diabetes. Each 1-SD increase in fasting plasma glucose, 2-h postload plasma glucose, and HbA1c conveyed 2.11-fold, 1.73-fold, and 1.81-fold higher risks of significant coronary stenosis, respectively, after adjustment for other conventional cardiovascular risk factors. CONCLUSIONS Using a noninvasive CAD diagnostic modality such as dual-source computed tomography coronary angiography, we detected a markedly elevated risk of significant coronary stenosis with early diabetes in asymptomatic Chinese adults.
The Deflation Limb of the Pressure–Volume Relationship in Infants during High-Frequency Ventilation
Authors: David G. Tingay, John F. Mills, Colin J. Morley, Anastasia Pellicano, Peter A. Dargaville
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: The importance of applying high-frequency oscillatory ventilation with a high lung volume strategy in infants is well established. Currently, a lack of reliable methods for assessing lung volume limits clinicians' ability to achieve the optimum volume range.Objectives: To map the pressure–volume relationship of the lung during high-frequency oscillatory ventilation in infants, to determine at what point ventilation is being applied clinically, and to describe the relationship between airway pressure, lung volume, and oxygenation.Methods: In 12 infants, a partial inflation limb and the deflation limb of the pressure–volume relationship were mapped using a quasi-static lung volume optimization maneuver. This involved stepwise airway pressure increments to total lung capacity, followed by decrements until the closing pressure of the lung was identified.Measurements and Main Results: Lung volume and oxygen saturation were recorded at each airway pressure. Lung volume was measured using respiratory inductive plethysmography. A distinct deflation limb could be mapped in each infant. Overall, oxygenation and lung volume were improved by applying ventilation on the deflation limb. Maximal lung volume and oxygenation occurred on the deflation limb at a mean airway pressure of 3 and 5 cm H2O below the airway pressure approximating total lung capacity, respectively.Conclusions: Using current ventilation strategies, all infants were being ventilated near the inflation limb. It is possible to delineate the deflation limb in infants receiving high-frequency oscillatory ventilation; in doing so, greater lung volume and oxygenation can be achieved, often at lower airway pressures.
Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation
Authors: Scott K. Fung, Pietro Andreone, Steve H. Han, K. Rajender Reddy, Arie Regev, Emmet B. Keeffe, Munira Hussain, Carmela Cursaro, Pamela Richtmyer, Jorge A. Marrero, Anna S.F. Lok
Journal: Journal of Hepatology (2005)
In this series we ask one or more experts to review a case. They are provided with information on which further management is to be based, and asked to explain their rationale, using the available evidence in the literature. What was actually done in the case is then revealed. A 68-year-old Man with Two Small Colon Polyps
Authors: J H Bond, J Baillie
Journal: Endoscopy (2000)

I am pleased to welcome Dr John Bond as our guest discussant. Dr Bond is Professor of Medicine at the University of Minnesota and Chief of the Gastroenterology Division at the Minneapolis Veterans' Administration Medical Center. His main claim to fame is, of course, having been a former teacher of mine. However, he is also recognized nationally and internationally as an expert in colon disorders, especially the management of colon polyps and screening for colon cancer. He brings a wealth of experience to the discussion of this case.