tbuckley/cabot-search huggingface dataset:
Apolipoprotein C-III and the Metabolic Basis for Hypertriglyceridemia and the Dense Low-Density Lipoprotein Phenotype
Authors: Chunyu Zheng, Christina Khoo, Jeremy Furtado, Frank M. Sacks
Journal: Circulation (2010)

Background— Here, we aim to identify defects of apolipoprotein (apo) B lipoprotein metabolism that characterize hypertriglyceridemia, focusing on apoC-III and apoE. Methods and Results— We studied the transport of plasma apoB within 21 distinct subfractions as separated by anti–apoC-III and anti–apoE immunoaffinity chromatography and ultracentrifugation in 9 patients with moderate hypertriglyceridemia and 12 normotriglyceridemic control subjects. Hypertriglyceridemia was characterized by a 3-fold higher liver secretion of very low-density lipoprotein (VLDL) that had apoC-III but not apoE and a 50% lower secretion of VLDL with both apoC-III and apoE (both P &lt;0.05). This shift in VLDL secretion pattern from apoE to apoC-III resulted in significantly reduced clearance of light VLDL (−39%; P &lt;0.05), compatible with the antagonizing effects of apoC-III on apoE-induced clearance of triglyceride-rich lipoproteins. In addition, rate constants for clearance were reduced for apoE-containing triglyceride-rich lipoproteins in hypertriglyceridemia, associated with increased apoC-III contents of these particles. LDL distribution shifted from light and medium LDL to dense LDL in hypertriglyceridemia through a quartet of kinetic perturbations: increased flux from apoC-III–containing triglyceride-rich lipoproteins, a shift in liver LDL secretion pattern from light to dense LDL, an increased conversion rate from light and medium LDL to dense LDL, and retarded catabolism of dense LDL. Conclusions— These results support a central role for apoC-III in metabolic defects leading to hypertriglyceridemia. Triglyceride-rich lipoprotein metabolism shifts from an apoE-dominated system in normotriglyceridemic participants characterized by rapid clearance from circulation of VLDL to an apoC-III–dominated system in hypertriglyceridemic patients characterized by reduced clearance of triglyceride-rich lipoproteins and the formation of the dense LDL phenotype.
Early Complication Rates in a Single-Surgeon Series of 2500 Robotic-Assisted Radical Prostatectomies: Report Applying a Standardized Grading System
Authors: Rafael F. Coelho, Kenneth J. Palmer, Bernardo Rocco, Ravendra R. Moniz, Sanket Chauhan, Marcelo A. Orvieto, Geoff Coughlin, Vipul R. Patel
Journal: European Urology (2010)
Collagen type Iα1 and vitamin D receptor gene polymorphisms and bone mass in primary biliary cirrhosis
Authors: A Parés
Journal: Hepatology (2001)

The potential influence of two gene polymorphisms, vitamin D receptor gene (VDR) and the gene encoding collagen type Ialpha1 (COLIA1) Sp1 polymorphisms, in the reduced bone mass observed in patients with primary biliary cirrhosis (PBC) was assessed in 61 women with PBC (age, 54.1 +/- 1.1 years) by restriction enzyme digestion of polymerase chain reaction (PCR)-amplified DNA extracted from whole blood. Bone mineral density (BMD) of the lumbar spine (L2-L4) and proximal femur were measured by X-ray absorptiometry. The severity of liver disease and cholestasis was also evaluated, and changes in BMD were calculated after a mean period of 2.9 +/- 0.3 years in 41 patients. Sixteen patients (26 %) had the BB, 20 the bb (33 %), and 25 Bb (41%) VDR genotypes. There were no significant baseline BMD differences among the 3 VDR genotypes. Forty-one patients (68%) had the SS, 16 the Ss (27%), and 3 the ss (5%) COLIA1 genotypes. The baseline lumbar BMD was significantly lower in patients having the s allele than in the homozygote SS patients (Z-score, -0.76 +/- 0.24 vs. -0.10 +/- 0.17, P =.02). The severity of cholestasis was not related to the VDR or COLIA1 1 polymorphisms. Lumbar bone loss was independent of VDR and COLIA1 genotypes, but it was associated with cholestasis. In conclusion, the COLIA1 but not VDR polymorphism is a genetic marker of peak bone mass in patients with PBC, although the severity of cholestasis is the main factor for osteoporosis since it is associated with the rate of bone loss.
Serum Apolipoprotein A-I and Large High-Density Lipoprotein Particles Are Positively Correlated with FEV<sub>1</sub> in Atopic Asthma
Authors: Amisha V. Barochia, Maryann Kaler, Rosemarie A. Cuento, Elizabeth M. Gordon, Nargues A. Weir, Maureen Sampson, Joseph R. Fontana, Sandra MacDonald, Joel Moss, Vincent Manganiello, Alan T. Remaley, Stewart J. Levine
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Although lipids, apolipoproteins, and lipoprotein particles are important modulators of inflammation, varying relationships exist between these parameters and asthma.To determine whether serum lipids and apolipoproteins correlate with the severity of airflow obstruction in subjects with atopy and asthma.Serum samples were obtained from 154 atopic and nonatopic subjects without asthma, and 159 subjects with atopy and asthma. Serum lipid and lipoprotein levels were quantified using standard diagnostic assays and nuclear magnetic resonance (NMR) spectroscopy. Airflow obstruction was assessed by FEV1% predicted.Serum lipid levels correlated with FEV1 only in the subjects with atopy and asthma. Serum levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) were positively correlated with FEV1 in subjects with atopy and asthma, whereas a negative correlation existed between FEV1 and serum levels of triglycerides, low-density lipoprotein (LDL) cholesterol, apolipoprotein B (apoB), and the apoB/apoA-I ratio. NMR spectroscopy identified a positive correlation between FEV1 and HDLNMR particle size, as well as the concentrations of large HDLNMR particles and total IDLNMR (intermediate-density lipoprotein) particles in subjects with atopy and asthma. In contrast, LDLNMR particle size and concentrations of LDLNMR and VLDLNMR (very-low-density lipoprotein) particles were negatively correlated with FEV1 in subjects with atopy and asthma.In subjects with atopy and asthma, serum levels of apoA-I and large HDLNMR particles are positively correlated with FEV1, whereas serum triglycerides, LDL cholesterol, and apoB are associated with more severe airflow obstruction. These results may facilitate future studies to assess whether apoA-I and large HDLNMR particles can reduce airflow obstruction and disease severity in asthma.
Randomized International Phase III Trial of ERCC1 and RRM1 Expression–Based Chemotherapy Versus Gemcitabine/Carboplatin in Advanced Non–Small-Cell Lung Cancer
Authors: Gerold Bepler, Charles Williams, Michael J. Schell, Wei Chen, Zhong Zheng, George Simon, Shirish Gadgeel, Xiuhua Zhao, Fred Schreiber, Julie Brahmer, Alberto Chiappori, Tawee Tanvetyanon, Mary Pinder-Schenck, Jhanelle Gray, Eric Haura, Scott Antonia, Juergen R. Fischer
Journal: Journal of Clinical Oncology (2013)

Purpose We assessed whether chemotherapy selection based on in situ ERCC1 and RRM1 protein levels would improve survival in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Eligible patients were randomly assigned 2:1 to the trial's experimental arm, which consisted of gemcitabine/carboplatin if RRM1 and ERCC1 were low, docetaxel/carboplatin if RRM1 was high and ERCC1 was low, gemcitabine/docetaxel if RRM1 was low and ERCC1 was high, and docetaxel/vinorelbine if both were high. In the control arm, patients received gemcitabine/carboplatin. The trial was powered for a 32% improvement in 6-month progression-free survival (PFS). Results Of 331 patients registered, 275 were eligible. The median number of cycles given was four in both arms. A tumor rebiopsy specifically for expression analysis was required in 17% of patients. The median time from informed consent to expression analysis was 11 days. We found no statistically significant differences between the experimental arm and the control arm in PFS (6.1 months v 6.9 months) or overall survival (11.0 months v 11.3 months). A subset analysis revealed that patients with low levels for both proteins who received the same treatment in both treatment arms had a statistically better PFS (P = .02) in the control arm (8.1 months) compared with the experimental arm (5.0 months). Conclusion This demonstrates that protein expression analysis for therapeutic decision making is feasible in newly diagnosed patients with advanced-stage NSCLC. A tumor rebiopsy is safe, required in 17%, and acceptable to 89% (47 of 53) of patients.
New drug pricing scheme could politicise decisions and reduce access, says think tank
Authors: A. O'Dowd
Journal: BMJ (2013)

The new proposed drug pricing scheme for the United Kingdom known as value based pricing could turn patients into “political pawns” and make it harder for them to get some drugs, an independent healthcare think tank has said.

The think tank, 2020health, published a report on 7 May in which it raises several concerns about the government’s plan to change the way that drugs are priced from next year.1 The report examines the implications of the new arrangements for patients.

Under the current system for pricing drugs, known as the Pharmaceutical Price Regulation Scheme (PPRS), the price of individual drugs is not controlled, but companies’ total revenue from the NHS is limited.

The new system of value based pricing, which is due to be …
Systolic blood pressure and mortality in patients with atrial fibrillation and heart failure: insights from the <scp>AFFIRM</scp> and <scp>AF‐CHF</scp> studies
Authors: Maxime Tremblay‐Gravel, Paul Khairy, Denis Roy, Hugues Leduc, D. George Wyse, Julia Cadrin‐Tourigny, Laurent Macle, Marc Dubuc, Jason Andrade, Lena Rivard, Peter G. Guerra, Bernard Thibault, Ali Ahmed, Mario Talajic, Marie‐Claude Guertin, Michel White
Journal: European Journal of Heart Failure (2014)
Integrative and comparative genomics analysis of early hepatocellular carcinoma differentiated from liver regeneration in young and old
Authors: Dilek Colak, Muhammad A Chishti, Al-Bandary Al-Bakheet, Ahmed Al-Qahtani, Mohamed M Shoukri, Malcolm H Goyns, Pinar T Ozand, John Quackenbush, Ben H Park, Namik Kaya
Journal: Molecular Cancer (2010)

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. To identify distinct molecular mechanisms for early HCC we developed a rat model of liver regeneration post-hepatectomy, as well as liver cells undergoing malignant transformation and compared them to normal liver using a microarray approach. Subsequently, we performed cross-species comparative analysis coupled with copy number alterations (CNA) of independent early human HCC microarray studies to facilitate the identification of critical regulatory modules conserved across species. We identified 35 signature genes conserved across species, and shared among different types of early human HCCs. Over 70% of signature genes were cancer-related, and more than 50% of the conserved genes were mapped to human genomic CNA regions. Functional annotation revealed genes already implicated in HCC, as well as novel genes which were not previously reported in liver tumors. A subset of differentially expressed genes was validated using quantitative RT-PCR. Concordance was also confirmed for a significant number of genes and pathways in five independent validation microarray datasets. Our results indicated alterations in a number of cancer related pathways, including p53, p38 MAPK, ERK/MAPK, PI3K/AKT, and TGF-β signaling pathways, and potential critical regulatory role of MYC, ERBB2, HNF4A, and SMAD3 for early HCC transformation. The integrative analysis of transcriptional deregulation, genomic CNA and comparative cross species analysis brings new insights into the molecular profile of early hepatoma formation. This approach may lead to robust biomarkers for the detection of early human HCC.
Sister chromatid exchange analysis in the lymphocytes of patients with ankylosing spondylitis
Authors: S. Sonmez
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> This study investigated whether any genomic change occurs in DNA level in ankylosing spondylitis (AS) by measuring sister chromatid exchange (SCE) frequency. <h3>METHODS</h3> SCE frequency was detected on metaphase chromosomes obtained from peripheral blood lymphocyte cultures in 15 patients diagnosed as having AS. SCE values were also obtained from 15 healthy subjects as a control group. SCE frequencies were detected from metaphases obtained from standard blood cultures by using bromodeoxyuridine and staining by Giemsa. <h3>RESULTS</h3> SCE frequencies of AS were statistically higher than those of the control group (p&lt;0.005). <h3>CONCLUSION</h3> These results suggest that genetic factors may play a more important part than realised in the aetiology of AS.
STUDIES ON THE SOLUBLE PRECIPITABLE SUBSTANCES OF VACCINIA
Authors: F. O. Wishart, James Craigie
Journal: The Journal of Experimental Medicine (1936)

Observations on antibody production in the rabbit in response to the injection of the LS antigen of vaccinia have shown that this antigen retains its ability to stimulate the production of L and S antibodies, not only when it is in a state of solution as found in lapine Seitz filtrates, but also after it has been partially purified. As reported in previous papers, both the L and S antibodies participate (a) in the true agglutination of washed elementary bodies, (b) in the precipitation of the soluble LS antigen found in fresh vaccine suspensions or dissociated in vitro from washed elementary bodies. The difference in the thermostability of the L and S components of the LS antigen as far as their reactivity in vitro is concerned, holds in respect of their capacity to stimulate antibody production. Heating at 70 degrees C. invariably abolishes the antigenicity of the L component while the S component remains antigenic after being heated to 90 degrees C.
Risk prediction and end-points in idiopathic pulmonary fibrosis: one step at a time
Authors: Christopher J. Ryerson
Journal: European Respiratory Journal (2014)

Predicting mortality in IPF: a commentary on new data showing the prognostic importance of 6-min walking distance http:// http://ow.ly/tCD0NIdiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a median survival of approximately 3 years from diagnosis.Accurate prediction of mortality is important in IPF, as it helps determine the urgency of lung transplantation, guides other management and end-of-life decisions, and facilitates enrichment of clinical trial populations.Although most patients with IPF die from progressive respiratory failure [1], predicting outcomes is challenging due to the heterogeneity of disease progression.In this issue of the European Respiratory Journal, DU BOIS et al. [2] use the INSPIRE (International Study of Survival Outcomes in Idiopathic Pulmonary Fibrosis with Interferon-c-1b) dataset to describe a new prediction model that estimates mortality in IPF.The INSPIRE study was a multicentre double-blind randomised trial comparing interferon-c-1b to placebo in 826 patients with mild to moderate IPF [3]. This trial did not meet its primary end-point but has generated high-quality data that continue to provide valuable insight into the progression of IPF.DU BOIS et al. [4] have previously used the INSPIRE data to show that age, baseline forced vital capacity (FVC), 24-week change in FVC, and recent respiratory hospitalisation independently predict 1-year mortality in patients with IPF [4].These authors have now extended their findings by showing that mortality prediction is improved by adding both baseline and 24-week change in 6-min walking distance (6MWD) to this multivariate model [2].This new study is a noteworthy addition to the literature, providing important data on the prediction of mortality in IPF and suggesting potential options for clinical trial end-points. Defining mortality risk in IPFThe model developed by DU BOIS et al. [2] accurately estimates 1-year mortality in patients with IPF with a C-statistic of 0.80.The C-statistic, or C-index, is a measure of how well a model predicts the risk of an outcome (e.g.1-year mortality) in any two individuals randomly selected from the cohort of interest.A Cstatistic of 1.0 indicates that the model appropriately identifies the individual at higher risk of the outcome in every paired comparison.A C-statistic above 0.70 is generally considered acceptable, and a C-statistic of 0.50 indicates that the prediction model performs no better than chance.The C-statistic of 0.80 in this study compares favourably with models that are in routine clinical use in other fields and other validated models in IPF [5].It is therefore tempting to use this new model in the clinical setting; however, there are some questions that require further study.
Effect of Intensive Handwashing Promotion on Childhood Diarrhea in High-Risk Communities in Pakistan
Authors: Stephen P Luby, Mubina Agboatwalla, John Painter, Arshad Altaf, Ward L Billhimer, Robert M Hoekstra
Journal: JAMA (2004)

Washing hands with soap prevents diarrhea, but children at the highest risk of death from diarrhea are younger than 1 year, too young to wash their own hands. Previous studies lacked sufficient power to assess the impact of household handwashing on diarrhea in infants.To evaluate the effect of promoting household handwashing with soap among children at the highest risk of death from diarrhea.A cluster randomized controlled trial of 36 low-income neighborhoods in urban squatter settlements in Karachi, Pakistan. Field workers visited participating households at least weekly from April 15, 2002, to April 5, 2003. Eligible households located in the study area had at least 2 children younger than 15 years, at least 1 of whom was younger than 5 years.Weekly visits in 25 neighborhoods to promote handwashing with soap after defecation and before preparing food, eating, and feeding a child. Within intervention neighborhoods, 300 households (1523 children) received a regular supply of antibacterial soap and 300 households (1640 children) received plain soap. Eleven neighborhoods (306 households and 1528 children) comprised the control group.Incidence density of diarrhea among children, defined as the number of diarrheal episodes per 100 person-weeks of observation.Children younger than 15 years living in households that received handwashing promotion and plain soap had a 53% lower incidence of diarrhea (95% confidence interval [CI], -65% to -41%) compared with children living in control neighborhoods. Infants living in households that received handwashing promotion and plain soap had 39% fewer days with diarrhea (95% CI, -61% to -16%) vs infants living in control neighborhoods. Severely malnourished children (weight for age z score, <-3.0) younger than 5 years living in households that received handwashing promotion and plain soap had 42% fewer days with diarrhea (95% CI, -69% to -16%) vs severely malnourished children in the control group. Similar reductions in diarrhea were observed among children living in households receiving antibacterial soap.In a setting in which diarrhea is a leading cause of child death, improvement in handwashing in the household reduced the incidence of diarrhea among children at high risk of death from diarrhea.
The Phylogenetic Positions of Three Basal-Hexapod Groups (Protura, Diplura, and Collembola) Based on Ribosomal RNA Gene Sequences
Authors: Yun-Xia Luan, Jon M Mallatt, Rong-Dong Xie, Yi-Ming Yang, Wen-Ying Yin
Journal: Molecular Biology and Evolution (2005)

This study combined complete 18S with partial 28S ribosomal RNA gene sequences ( approximately 2,000 nt in total) to investigate the relations of basal hexapods. Ten species of Protura, 12 of Diplura, and 10 of Collembola (representing all subgroups of these three clades) were sequenced, along with 5 true insects and 8 other arthropods, which served as out-groups. Trees were constructed with maximum parsimony, maximum likelihood, Bayesian analysis, and minimum-evolution analysis of LogDet-transformed distances. All methods yielded strong support for a clade of Protura plus Diplura, here named Nonoculata, and for monophyly of the Diplura. Parametric-bootstrapping analysis showed our data to be inconsistent with previous hypotheses (P < 0.01) that joined Protura with Collembola (Ellipura), that said Diplura are sister to true insects or are diphyletic, and that said Collembola are not hexapods. That is, our data are consistent with hexapod monophyly and Collembola grouped weakly with "Protura + Diplura" under most analytical conditions. As a caveat to the above conclusions, the sequences showed nonstationarity of nucleotide frequencies across taxa, so the CG-rich sequences of the diplurans and proturans may have grouped together artifactually; however, the fact that the LogDet method supported this group lessens this possibility. Within the basal hexapod groups, where nucleotide frequencies were stationary, traditional taxonomic subgroups generally were recovered: i.e., within Protura, the Eosentomata and Acerentomata (but Sinentomata was not monophyletic); within Collembola, the Arthropleona, Poduromorpha, and Entomobryomorpha (but Symphypleona was polyphyletic); and in Diplura, the most complete data set (> 2,100 nt) showed monophyly of Campodeoidea and of Japygoidea, and most methods united Projapygoidea with Japygoidea.
Reproducibility of the First-Phase Insulin Response to Intravenous Glucose Is Not Improved by Retrograde Cannulation and Arterialization or the Use of a Lower Glucose Dose
Authors: Peter D McNair, Peter G Colman, Frank P Alford, Leonard C Harrison
Journal: Diabetes Care (1995)

OBJECTIVE To determine whether the reproducibility of the first-phase insulin response (FPIR) measured during an intravenous glucose tolerance test is improved by the use of a lower glucose dose or retrograde sampling from an arterialized hand vein. RESEARCH DESIGN AND METHODS Previous studies have suggested that the high within-subject variation of FPIR measurement of up to 110% could be reduced by sampling from a retrograde cannulated and arterialized hand vein opposite to the cubital fossa vein through which the glucose was injected or by the use of a lower dose of glucose. Two low-dose (glucose, 5 g/m2 injected over 30 s) and two standard Islet Cell Antibody Registry Users Study (ICARUS) (glucose, 0.5 g/kg injected over 3 min) tests were performed on seven normal subjects at 2-week intervals. Samples were collected simultaneously from the cubital fossa vein, through which the glucose was injected, and from a retrograde cannulated, contralateral hand vein that was arterialized by heating. FPIR was expressed as the sum of the insulin measurements 1 and 3 min after the completion of the glucose injection and as the area under the insulin curve between 0 and 10 min. RESULTS Responses to the mean sum of serum insulin concentrations at 1 and 3 min after intravenous glucose were significantly lower for the low-dose test (mean 94 mU/l) than for the high-dose test (mean 184 mU/l) for samples taken from the arm (P &amp;lt; 0.05); mean 0- to 10-min insulin areas were 367 and 596 mU/l for low- and high-dose tests, respectively (P &amp;lt; 0.05). Within-subject coefficients of variation for samples from the hand or the arm ranged from 0.33 to 17.5% and 1.3 to 38% for successive ICARUS and low-dose tests, respectively. Reproducibility, measured by the coefficient of variation between successive tests for each protocol, was not significantly different using samples taken from the arm or the contralateral hand. CONCLUSIONS The intravenous glucose tolerance test is reproducible when performed by the same operator over a short time span. Reproducibility is not significantly improved by sampling from an arterialized, retrograde cannulated, contralateral hand vein. There is no case for changing the present ICARUS protocol to incorporate retrograde cannulation or low-dose (5 g/m2) glucose.