tbuckley/cabot-search huggingface dataset:
Anti-perinuclear factor compared with the so called "antikeratin" antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritides
Authors: C. Vincent, F. de Keyser, C. Masson-Bessiere, M. Sebbag, E. M Veys, G. Serre
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Antiperinuclear factor (APF), "antikeratin antibodies" ("AKA"), and antibodies to human epidermis filaggrin (AFA), are highly specific serological markers of rheumatoid arthritis (RA), which recognise epitopes on various isoforms of (pro)filaggrin. It was proposed that these antibodies are globally named antifilaggrin autoantibodies. Here the diagnostic value of the detection of each one is compared and the overlap between the three tests evaluated. <h3>METHODS</h3> 492 serum samples were tested, including 279 RA serum samples, taken from patients in France and Belgium. APF and "AKA" titres were estimated by indirect immunofluorescence, and AFA titres by immunoblotting on filaggrin enriched human epidermis extracts. <h3>RESULTS</h3> By a convenient choice of the positivity thresholds, the diagnostic sensitivity and specificity of the tests were shown to be similar (0.52 and 0.97, respectively). Although the antibody titres were strongly correlated, the associations APF-AFA or AFA-"AKA" permitted more than 52% or 55% of RA to be diagnosed, with a specificity of 0.99. <h3>CONCLUSION</h3> APF, "AKA", and AFA detection have a similar diagnostic value. However, because the three tests do not totally overlap, associating APF with "AKA" or AFA with "AKA" can improve diagnostic sensitivity. None of the three antigens used bear all the epitopes recognised by anti-filaggrin autoantibodies.
NHS doesn't know how many managers were made redundant and rehired after coalition's changes
Authors: A. O'Dowd
Journal: BMJ (2013)

The NHS has no way of knowing how many managers have been made redundant and rehired, because the figures are not collected, NHS England’s chief executive told MPs this week when he appeared before the parliamentary health committee.

The MPs asked David Nicholson what the cost had been of making people redundant and then rehiring them as a result of the government’s reorganisation of the NHS.

Nicholson said, “In terms of NHS England, as far as we know—and we employ over 5000 people—no one has been rehired after taking a redundancy package by NHS England.”

However, he admitted that no one would know exactly how many people had been made redundant and then rehired somewhere in the NHS as a result of the reorganisation instigated by the …
Oxidative modifications, mitochondrial dysfunction, and impaired protein degradation in Parkinson's disease: how neurons are lost in the Bermuda triangle
Authors: Kristen A Malkus, Elpida Tsika, Harry Ischiropoulos
Journal: Molecular Neurodegeneration (2009)

While numerous hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of neurodegenerative diseases, the theory of oxidative stress has received considerable support. Although many correlations have been established and encouraging evidence has been obtained, conclusive proof of causation for the oxidative stress hypothesis is lacking and potential cures have not emerged. Therefore it is likely that other factors, possibly in coordination with oxidative stress, contribute to neuron death. Using Parkinson's disease (PD) as the paradigm, this review explores the hypothesis that oxidative modifications, mitochondrial functional disruption, and impairment of protein degradation constitute three interrelated molecular pathways that execute neuron death. These intertwined events are the consequence of environmental exposure, genetic factors, and endogenous risks and constitute a "Bermuda triangle" that may be considered the underlying cause of neurodegenerative pathogenesis.
Properties of reticulum cell sarcomas in SJL/J mice. V. Nature of reticulum cell sarcoma surface antigen which induces proliferation of normal SJL/J T cells.
Authors: N M Ponzio, C S David, D C Shreffler, G J Thorbecke
Journal: The Journal of Experimental Medicine (1977)

The results of studies on the reticulum cell sarcoma (RCS) tumors of SJL/J mice presented here, indicate that spontaneous tumors, which arise in older mice, also possess the capacity to induce the vigorous proliferative response in syngenetic T lymphocytes that are characteristic of the transplantable RCS lines. Analysis of cell surface antigens revealed the presence of Ia determinats on gradient-purified transplantable RCS tumor cells; however, these cells did not express Thy 1.2, nIg, or, any of the viral proteins that were tested for by specific antisera. Pretreatment of RCS cells with anti-Ia sera and complement-deleted cells that were stimulatory for syngenetic T lymphocytes, and addition of anti-Ia sera directly to cultures blocked the proliferative response at the stimulator (RCS) cell level. Lymph node cells from H-2(8) strains other than SJL/J, including A.SW and B10.S also gave proliferative responses to RCS cells, although lower in magnitude. A requirement on the part of responding cells for identity with RCS cells at the Ir region was indicated by the finding that A.TH but not A.TL lymph node cells responded to RCS. It is concluded that RCS cells stimulate Ir-region identical T cells (without evidence of presensitization) through a modification in the expression of Ia antigens on the surface of the tumor cells.
C3H-&lt;italic&gt;A&lt;/italic&gt;&lt;sup&gt;&lt;italic&gt;uv&lt;/italic&gt;&lt;/sup&gt;—A High Hepatoma and High Mammary Tumor Strain of Mice
Authors: W. E. Heston, G. Vlahakis
Journal: JNCI Journal of the National Cancer Institute (1968)

The C3H-Auv is the highest mammary tumor and highest hepatoma strain of mice we have had. All breeding and virgin C3H-Auv females with the mammary tumor virus (MTV) developed mammary tumors at an average age of between 6 and 7 months. Of the C3H-AuvfB females, presumably free of MTV but with nodule-inducing virus (NIV), 90% of the breeders and 20% of the virgins developed mammary tumors at an average age of 15 months. All C3H-Auvmales can be expected to have hepatomas by about 12 months of age or soon thereafter, and nearly all C3H-AuvfB females, since they do not die early with mammary tumors, will also develop hepatomas. The hepatomas arose about 4 months later in the females than in the males. The Auvgene by which this strain is characterized, and that, as we reported earlier, increases occurrence of mammary tumors, increased the incidence of hepatomas, caused them to arise earlier, and caused more hepatomas in each animal. The effect of this gene on increasing occurrence of tumors is correlated with its effect on increasing body weight.
Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir
Authors: Stefan Mauss, Dietrich Hueppe, Ulrich Alshuth
Journal: Hepatology (2013)

In clinical trials with telaprevir (TLV) and boceprevir (BOC) renal impairment was not reported as a relevant adverse event. The PAN study is a noninterventional study enrolling patients treated with peginterferon alfa-2a/ribavirin (PEG/RBV) with or without TVL or BOC. Here we restrict the analysis to hepatitis C virus genotype 1 patients having completed 12 (n = 895) or 24 weeks (n = 591) of treatment. For estimation of glomerular filtration rate (eGFR) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was chosen. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) more frequently experienced a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (P < 0.05). Risk factors associated with eGFR <60 mL/min in multiple logistic regression analysis were age (P < 0.001), arterial hypertension (P < 0.05), higher serum creatinine at baseline (P < 0.001), and being on triple therapy with TLV or BOC (P < 0.01). Patients with an eGFR of <60 mL/min had a lower absolute mean hemoglobin at week 12 compared to patients with an eGFR >60 mL/min (9.7 g/dL ± 1.4 g/dL versus 11.0 g/dL ± 1.7 g/dL) (P < 0.001). Most patients on TLV with a decrease of eGFR <60 mL/min showed a marked improvement in renal function after discontinuation of TLV. Conclusion: Renal impairment has not been reported as a safety signal in clinical trials with TVL or BOC. However, in this large cohort including patients with risk factors for renal impairment a marked decline in renal function was observed in about 5% of patients on triple therapy. In addition to being a safety concern, substantial ribavirin dose reductions have to be considered in these patients, as anemia was more pronounced in patients with impaired renal function. (Hepatology 2014;58:46–48)
Quality of Reporting of Serious Adverse Drug Events to an Institutional Review Board: A Case Study with the Novel Cancer Agent, Imatinib Mesylate
Authors: David A. Dorr, Rachel Burdon, Dennis P. West, Jennifer Lagman, Christina Georgopoulos, Steven M. Belknap, June M. McKoy, Benjamin Djulbegovic, Beatrice J. Edwards, Sigmund A. Weitzman, Simone Boyle, Martin S. Tallman, Moshe Talpaz, Oliver Sartor, Charles L. Bennett
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Serious adverse drug event (sADE) reporting to Institutional Review Boards (IRB) is essential to ensure pharmaceutical safety. However, the quality of these reports has not been studied. Safety reports are especially important for cancer drugs that receive accelerated Food and Drug Administration approval, like imatinib, as preapproval experience with these drugs is limited. We evaluated the quality, accuracy, and completeness of sADE reports submitted to an IRB. Experimental Design: sADE reports submitted to an IRB from 14 clinical trials with imatinib were reviewed. Structured case report forms, containing detailed clinical data fields and a validated causality assessment instrument, were developed. Two forms were generated for each ADE, the first populated with data abstracted from the IRB reports, and the second populated with data from the corresponding clinical record. Completeness and causality assessments were evaluated for each of the two sources, and then compared. Accuracy (concordance between sources) was also assessed. Results: Of 115 sADEs reported for 177 cancer patients to the IRB, overall completeness of adverse event descriptions was 2.4-fold greater for structured case report forms populated with information from the clinical record versus the corresponding forms from IRB reports (95.0% versus 40.3%, P &amp;lt; 0.05). Information supporting causality assessments was recorded 3.5-fold more often in primary data sources versus IRB adverse event descriptions (93% versus 26%, P &amp;lt; 0.05). Some key clinical information was discrepant between the two sources. Conclusions: The use of structured syndrome-specific case report forms could enhance the quality of reporting to IRBs, thereby improving the safety of pharmaceuticals administered to cancer patients.
Statins and progressive renal disease
Authors: Michele Buemi, Massimino Senatore, Francesco Corica, Carmela Aloisi, Adolfo Romeo, Emanuela Cavallaro, Fulvio Floccari, Domenico Tramontana, Nicola Frisina
Journal: Medicinal Research Reviews (2001)

Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans.
Costs of Health Care Administration in the United States and Canada
Authors: Steffie Woolhandler, Terry Campbell, David U. Himmelstein
Journal: New England Journal of Medicine (2003)

A decade ago, the administrative costs of health care in the United States greatly exceeded those in Canada. We investigated whether the ascendancy of computerization, managed care, and the adoption of more businesslike approaches to health care have decreased administrative costs.For the United States and Canada, we calculated the administrative costs of health insurers, employers' health benefit programs, hospitals, practitioners' offices, nursing homes, and home care agencies in 1999. We analyzed published data, surveys of physicians, employment data, and detailed cost reports filed by hospitals, nursing homes, and home care agencies. In calculating the administrative share of health care spending, we excluded retail pharmacy sales and a few other categories for which data on administrative costs were unavailable. We used census surveys to explore trends over time in administrative employment in health care settings. Costs are reported in U.S. dollars.In 1999, health administration costs totaled at least 294.3 billion dollars in the United States, or 1,059 dollars per capita, as compared with 307 dollars per capita in Canada. After exclusions, administration accounted for 31.0 percent of health care expenditures in the United States and 16.7 percent of health care expenditures in Canada. Canada's national health insurance program had overhead of 1.3 percent; the overhead among Canada's private insurers was higher than that in the United States (13.2 percent vs. 11.7 percent). Providers' administrative costs were far lower in Canada. Between 1969 and 1999, the share of the U.S. health care labor force accounted for by administrative workers grew from 18.2 percent to 27.3 percent. In Canada, it grew from 16.0 percent in 1971 to 19.1 percent in 1996. (Both nations' figures exclude insurance-industry personnel.)The gap between U.S. and Canadian spending on health care administration has grown to 752 dollars per capita. A large sum might be saved in the United States if administrative costs could be trimmed by implementing a Canadian-style health care system.
Kinetic Analysis of Dynamic <sup>11</sup>C-Acetate PET/CT Imaging as a Potential Method for Differentiation of Hepatocellular Carcinoma and Benign Liver Lesions
Authors: Li Huo, Jinxia Guo, Yonghong Dang, Jinqiao Lv, Youjing Zheng, Fang Li, Qingguo Xie, Xiaoyuan Chen
Journal: Theranostics (2015)

Objective:The kinetic analysis of 11 C-acetate PET provides more information than routine one time-point static imaging.This study aims to investigate the potential of dynamic 11 C-acetate hepatic PET imaging to improve the diagnosis of hepatocellular carcinoma (HCC) and benign liver lesions by using compartmental kinetic modeling and discriminant analysis.Methods: Twenty-two patients were enrolled in this study, 6 cases were with well-differentiated HCCs, 7 with poorly-differentiated HCCs and 9 with benign pathologies.Following the CT scan, all patients underwent 11 C-acetate dynamic PET imaging.A three-compartment irreversible dual-input model was applied to the lesion time activity curves (TACs) to estimate the kinetic rate constants K 1 -k 3 , vascular fraction (VB) and the coefficient α representing the relative hepatic artery (HA) contribution to the hepatic blood supply on lesions and non-lesion liver tissue.The parameter Ki (=K 1 ×k 3 /(k 2 + k 3 )) was calculated to evaluate the local hepatic metabolic rate of acetate (LHMAct).The lesions were further classified by discriminant analysis with all the above parameters.Results: K 1 and lesion to non-lesion standardized uptake value (SUV) ratio (T/L) were found to be the parameters best characterizing the differences among well-differentiated HCC, poorly-differentiated HCC and benign lesions in stepwise discriminant analysis.With discriminant functions consisting of these two parameters, the accuracy of lesion prediction was 87.5% for well-differentiated HCC, 50% for poorly-differentiated HCC and 66.7% for benign lesions.The classification was much better than that with SUV and T/L, where the corresponding classification accuracy of the three kinds of lesions was 57.1%, 33.3% and 44.4%.Conclusion: 11 C-acetate kinetic parameter K 1 could improve the identification of HCC from benign lesions in combination with T/L in discriminant analysis.The discriminant analysis using static and kinetic parameters appears to be a very helpful method for clinical liver masses diagnosis and staging.
SWEETS IN CHILDHOOD
Authors: J. S. Wallace
Journal: BMJ (1911)

<h3>Abstract</h3> The amount of mental effort we invest in a task is influenced by the reward we can expect if we perform that task well. However, some of the rewards that have the greatest potential for driving these efforts (e.g., jobs, grants) are partly determined by factors beyond one’s control. In such cases, effort has more limited <i>efficacy</i> for obtaining rewards. We have proposed that people integrate information about the expected reward and efficacy for effort to determine the expected value of control, and then adjust their control allocation (i.e. mental effort) accordingly. Here we test this theory’s key behavioral and neural predictions. We show that participants invest more control when this control is more rewarding and more efficacious, and that these incentive components separately modulate EEG signatures of incentive evaluation and proactive control allocation. Our findings support the prediction that people combine worth and worthwhileness to determine how much effort to invest.
Maternal and child undernutrition and overweight in low-income and middle-income countries
Authors: Robert E Black, Cesar G Victora, Susan P Walker, Zulfiqar A Bhutta, Parul Christian, Mercedes de Onis, Majid Ezzati, Sally Grantham-McGregor, Joanne Katz, Reynaldo Martorell, Ricardo Uauy
Journal: The Lancet (2013)
Hypoxia Regulates Bone Morphogenetic Protein Signaling Through C-Terminal–Binding Protein 1
Authors: Xinqi Wu, Mun Seog Chang, S. Alex Mitsialis, Stella Kourembanas
Journal: Circulation Research (2006)

Bone morphogenetic protein receptor 2 (BMPR2) mutations have been linked to familial pulmonary arterial hypertension (PAH), but the molecular pathways leading to this severe pathology remain poorly characterized. We report that hypoxia, a paramount stimulus for the development of pulmonary hypertension, suppresses the expression of inhibitor of differentiation 1 (Id1), a downstream target of the BMPR2 pathway, in human pulmonary artery smooth muscle cells (HPASMC). This attenuation of BMP signaling by hypoxia is conveyed through a repression of the transcriptional activity of the BMP responsive element (BRE) through mechanisms involving the transcriptional corepressor C-terminal-binding protein 1 (CtBP-1) and histone deacetylases (HDACs). Concordantly, overexpression of CtBP-1 suppressed BMP signaling, whereas small interfering RNA against CtBP-1 efficiently enhanced BMP stimulation of Id1 gene expression. Scavengers of reactive oxygen species had no effect on the hypoxic regulation of Id1, but, significantly, enhancement of the intracellular NADH/NAD(+) ratio mimicked the effects of hypoxia. These results indicate that attenuation of BMP signaling can occur through modulation of CtBP-1 activity by hypoxia-induced changes in the NADH/NAD(+) ratio. Our findings, taken in context with the observed prevalence of pulmonary arterial hypertension associated with BMPR2 mutations, define converging molecular pathways that lead to the development of pulmonary hypertension, through either genetic or epigenetic loss of function of components of the BMP signaling pathway.
MADS-Box Genes in Ginkgo biloba and the Evolution of the AGAMOUS Family
Authors: Muriel Jager, Alexandre Hassanin, Michael Manuel, Hervé Le Guyader, Jean Deutsch
Journal: Molecular Biology and Evolution (2003)

MADS-box proteins are a large family of transcription factors. In plants, many genes belonging to this family are involved in the homeosis of the floral system. Up to now, they have mainly been studied in angiosperms, especially in the model species Arabidopsis thaliana and Antirrhinum majus. We undertook a study of MADS-box genes in Ginkgo biloba, the unique extant representative of a whole branch of the phylogenetic tree of the seed plants. A polymerase chain reaction (PCR) survey reveals the diversity of MADS-box genes present in the genome of the Ginkgo. Duplications probably occurred specifically in the ginkgophyte lineage. Phylogenetic analyses revealed that one of these genes, GBM5, is an orthologue of the AGAMOUS gene of A. thaliana. We cloned and sequenced the entire cDNA of the GBM5 gene and studied its intron/exon structure. We showed by reverse transcriptase-PCR that it is expressed in both floral and vegetative tissues. We discuss the molecular evolution of the AGAMOUS family of genes.
Idiosyncratic Drug Reactions: Current Understanding
Authors: Jack Uetrecht
Journal: The Annual Review of Pharmacology and Toxicology (2006)

Clinical characteristics and circumstantial evidence suggest that idiosyncratic drug reactions are caused by reactive metabolites and are immune-mediated; however, there are few definitive data and there are likely exceptions. There are three principal hypotheses for how reactive metabolites might induce an immune-mediated idiosyncratic reaction: the hapten hypothesis, the danger hypothesis, and the PI hypothesis. It has been proposed that some idiosyncratic reactions, especially those involving the liver, represent metabolic idiosyncrasy; however, there are even less data to support this hypothesis. The unpredictable nature of these reactions makes mechanistic studies difficult. There is a very strong association with specific human leukocyte antigen (HLA) genes for certain reactions, but this has only been demonstrated for very few drugs. Animal models represent a very powerful tool for mechanistic studies, but the number of valid models is also limited. There may be biomarkers of risk; however, much more work needs to be done.
An Outbreak of Paratyphoid B Infection
Authors: S. C. Parry
Journal: BMJ (1942)

MEBIJOURNAL 661chance it seems possible that vasodilatation was more likely to occur in an individual with a small blood volume.The cases with a venous-pressure rise either had no clinical evidence of peripheral vasodilatation or only developed signs and symptoms of this after the rise was already considerable.The peripheral vasocilatation was not accompanied by the fall in venous pressure described by Murphy.Venous Pressure During the Transfusion of Cases of Pulmonary Disease
1178 A NANOBODY RECOGNIZING A NOVEL EPITOPE IN HEPATITIS C VIRUS GLYCOPROTEIN E2 BROADLY NEUTRALIZES VIRUS ENTRY AND INHIBITS CELL–CELL TRANSMISSION
Authors: A.W. Tarr, P. Lafaye, L. Damier-Piolle, L. Meredith, R.A. Urbanowicz, A. Meola, J.-L. Jestin, R.J.P. Brown, J.A. McKeating, F.A. Rey, J.K. Ball, T. Krey
Journal: Journal of Hepatology (2013)