tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Adding Granulocyte Colony-Stimulating Factor to Primary Prophylaxis With Antibiotics in Small-Cell Lung Cancer
Authors: Johanna N.H. Timmer-Bonte, Eddy M.M. Adang, Hans J.M. Smit, Bonne Biesma, Frank A. Wilschut, Gerben P. Bootsma, Theo M. de Boo, Vivianne C.G. Tjan-Heijnen
Journal: Journal of Clinical Oncology (2006)

Purpose Recently, a Dutch, randomized, phase III trial demonstrated that, in small-cell lung cancer patients at risk of chemotherapy-induced febrile neutropenia (FN), the addition of granulocyte colony-stimulating factor (GCSF) to prophylactic antibiotics significantly reduced the incidence of FN in cycle 1 (24% v 10%; P = .01). We hypothesized that selecting patients at risk of FN might increase the cost-effectiveness of GCSF prophylaxis. Methods Economic analysis was conducted alongside the clinical trial and was focused on the health care perspective. Primary outcome was the difference in mean total costs per patient in cycle 1 between both prophylactic strategies. Cost-effectiveness was expressed as costs per percent-FN-prevented. Results For the first cycle, the mean incremental costs of adding GCSF amounted to 681 euro (95% CI, −36 to 1,397 euro) per patient. For the entire treatment period, the mean incremental costs were substantial (5,123 euro; 95% CI, 3,908 to 6,337 euro), despite a significant reduction in the incidence of FN and related savings in medical care consumption. The incremental cost-effectiveness ratio was 50 euro per percent decrease of the probability of FN (95% CI, −2 to 433 euro) in cycle 1, and the acceptability for this willingness to pay was approximately 50%. Conclusion Despite the selection of patients at risk of FN, the addition of GCSF to primary antibiotic prophylaxis did not result in cost savings. If policy makers are willing to pay 240 euro for each percent gain in effect (ie, 3,360 euro for a 14% reduction in FN), the addition of GCSF can be considered cost effective.
Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex.
Authors: G M Shearer, T G Rehn, C A Garbarino
Journal: The Journal of Experimental Medicine (1975)

Splenic lymphocytes from four C57BL/10 congenic resistant mouse strains were sensitized in vitro with trinitrophenyl (TNP)-modified autologous spleen cellsmthe effector cells generated were incubated with 51-Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lympholysis determined. The results obtained using syngeneic-, congenic-, recombinante, and allogeneic-modified target cells indicated that TNP modification of the target cells was a necessary but insufficient requirement for lympholysis. Intra-H-2 homology either between modified stimulating cells and modified target cells or between responding lymphocytes and modified target cells was also important in the specificity for lysis. Homology at the K serological region or at K plus I-A in the B10.A and B10BR strains, and at either the D serological region or at some other region (possibly K) in the B10.D2 and C57BL/10 strains were shown to be necessary in order to detect lympholysis. Experiments using (B10itimes C57BL/10)F1 responding lymphocytes sensitized and assayed with TNP-modified parental cells indicated that the homology required for lympholysis was between modified stimulating and modified target cellsmthe possibility is raised that histocompatibility antigens may serve in the autologous system as cell surface components which are modified by viruses or autoimmune complexes to form cell-bound modified-self antigens, which are particularly suited for cell-mediated immune reactions. Evidence is presented suggesting that H-2-linked Ir genes are expressed in the TNP-modified autologous cytotoxic system. These findings imply that the major histocompatibility complex can be functionally involved both in the response potential to and in the formation of new antigenic determinants involving modified-self components.
Characterization and Regulation of Bv8 in Human Blood Cells
Authors: Cuiling Zhong, Xueping Qu, Martha Tan, Y. Gloria Meng, Napoleone Ferrara
Journal: Clinical Cancer Research (2009)

Bv8, also known as prokineticin 2, has been recently shown to be a mediator of myeloid cell-dependent tumor angiogenesis in mouse models. We wished to determine whether these findings might be potentially relevant to human disease.We characterized Bv8 expression in human blood cells in vitro and in vivo, and did Bv8 immunohistochemistry in human tumor sections. We also partially purified Bv8 from human neutrophils and tested its bioactivity.We found that Bv8 expression is regulated by several cytokines in a cell type-specific fashion. Both granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor induced Bv8 expression in neutrophils and bone marrow cells, whereas interleukin 10 up-regulated Bv8 expression in monocytes and lymphocytes. Bv8 potently promoted neutrophil chemotaxis. Bv8 protein isolated from human neutrophils was found to be biologically active. Of the two receptors for Bv8 [prokineticin receptor 1(PKR1)/endocrine gland-derived vascular endothelial growth factor receptor 1 (EG-VEGFR1) and PKR2/EG-VEGFR2], only PKR2/EG-VEGFR2 was detectable in human neutrophils. Also, we found a marked up-regulation of Bv8 mRNA and protein in peripheral blood mononuclear cells from G-CSF-treated donors compared with those from untreated individuals, verifying our in vitro observations. Finally, immunohistochemistry showed Bv8 expression in neutrophils infiltrating human tumors.These results provide the basis for further investigation of the pathophysiologic role of Bv8 in human tumors and inflammatory disorders and, potentially, for therapeutic application of Bv8 inhibitors.
Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity
Authors: Esti Yeger-Lotem, Laura Riva, Linhui Julie Su, Aaron D Gitler, Anil G Cashikar, Oliver D King, Pavan K Auluck, Melissa L Geddie, Julie S Valastyan, David R Karger, Susan Lindquist, Ernest Fraenkel
Journal: Nature Genetics (2009)
Weirdness is in the eye of the beholder
Authors: Will M. Bennis, Douglas L. Medin
Journal: Behavioral and Brain Sciences (2010)

Abstract Henrich et al.'s critical review demonstrating that psychology research is over-reliant on WEIRD samples is an important contribution to the field. Their stronger claim that “WEIRD subjects are particularly unusual” is less convincing, however. We argue that WEIRD people's apparent distinct weirdness is a methodological side-effect of psychology's over-reliance on WEIRD populations for developing its methods and theoretical constructs.
Bridging the gap: Dynamics as a unified view of cognition
Authors: Derek Harter, Arthur C. Graesser, Stan Franklin
Journal: Behavioral and Brain Sciences (2001)

Top-down dynamical models of cognitive processes, such as the one presented by Thelen et al., are important pieces in understanding the development of cognitive abilities in humans and biological organisms. Unlike standard symbolic computational approaches to cognition, such dynamical models offer the hope that they can be connected with more bottom-up, neurologically inspired dynamical models to provide a complete view of cognition at all levels. We raise some questions about the details of their simulation and about potential limitations of top-down dynamical models.
The Two Kidney to One Kidney Transition and Transplant Glomerulopathy
Authors: Yan Yang, Jeffrey B. Hodgin, Farsad Afshinnia, Su Q. Wang, Larysa Wickman, Mahboob Chowdhury, Ryuzoh Nishizono, Masao Kikuchi, Yihung Huang, Milagros Samaniego, Roger C. Wiggins
Journal: Journal of the American Society of Nephrology (2014)

The attrition rate of functioning allografts beyond the first year has not improved despite improved immunosuppression, suggesting that nonimmune mechanisms could be involved. Notably, glomerulopathies may account for about 40% of failed kidney allografts beyond the first year of engraftment, and glomerulosclerosis and progression to ESRD are caused by podocyte depletion. Model systems demonstrate that nephrectomy can precipitate hypertrophic podocyte stress that triggers progressive podocyte depletion leading to ESRD, and that this process is accompanied by accelerated podocyte detachment that can be measured in urine. Here, we show that kidney transplantation "reverse nephrectomy" is also associated with podocyte hypertrophy and increased podocyte detachment. Patients with stable normal allograft function and no proteinuria had levels of podocyte detachment similar to levels in two-kidney controls as measured by urine podocyte assay. By contrast, patients who developed transplant glomerulopathy had 10- to 20-fold increased levels of podocyte detachment. Morphometric studies showed that a subset of these patients developed reduced glomerular podocyte density within 2 years of transplantation due to reduced podocyte number per glomerulus. A second subset developed glomerulopathy by an average of 10 years after transplantation due to reduced glomerular podocyte number and glomerular tuft enlargement. Reduced podocyte density was associated with reduced eGFR, glomerulosclerosis, and proteinuria. These data are compatible with the hypothesis that podocyte depletion contributes to allograft failure and reduced allograft half-life. Mechanisms may include immune-driven processes affecting the podocyte or other cells and/or hypertrophy-induced podocyte stress causing accelerated podocyte detachment, which would be amenable to nonimmune therapeutic targeting.
Cytotoxic T-cell activation by polyribonucleotides: DNA synthesis is not required.
Authors: P H Bick, G Möller
Journal: The Journal of Experimental Medicine (1977)

We have shown that cytotoxic T cells can be polyclonally activated by a short exposure to complexes of polyadenylic:polyuridylic acid (poly A:U). Activation is optimal at a dose of 100 microgram/ml poly A:U and occurs during a 2 h incubation period in the absence of antigen. Killing of allogeneic, but not syngeneic, target cells can be observed after 12 h in culture and peaks after 21-24 h in the absence of any nonspecific binding ligand. The observed cytotoxicity is mediated by T lymphocytes and dose not require accessory macrophages or DNA synthesis for the activation or expression of effector functions. These results suggest that few requirements exist for the activation of cytotoxic T cells.
Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease
Authors: J. Bott, M.P. Carroll, J.H. Conway, S.E.J. Keilty, E.M. Ward, A.M. Brown, E.A. Paul, M.W. Elliott, R.C. Godfrey, J.A. Wedzicha, J. Moxham
Journal: The Lancet (1993)
Asian-American Variants of Human Papillomavirus 16 and Risk for Cervical Cancer: a Case-Control Study
Authors: J. Berumen, R. M. Ordonez, E. Lazcano, J. Salmeron, S. C. Galvan, R. A. Estrada, E. Yunes, A. Garcia-Carranca, G. Gonzalez-Lira, A. Madrigal-de la Campa
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Human papillomavirus 16 (HPV16) has a number of variants, each with a different geographic distribution and some that are associated more often with invasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants. Methods: Cervical samples were collected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV classes and subclasses were identified by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor characteristics were also collected. All statistical tests were two-sided. Results: HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically significantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects for either E or AA variants, χ2 test). However, the frequency of AA variants was 21 times higher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P = .006, χ2 test). The odds ratio (OR) for cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 ± 12.5 years [mean ± standard deviation]) were 7.7 years younger than E-positive case patients (53.9 ± 12.2 years) (P = .004, Student's t test). AA variants were associated with squamous cell carcinomas and adenocarcinomas, but E variants were associated with only squamous cell carcinomas (P = .014, Fisher's exact test). Conclusions: The high frequency of HPV16 AA variants, which appear to be more oncogenic than E variants, might contribute to the high incidence of cervical cancer in Mexico.
Oestrogens inhibit interleukin 1 -mediated nitric oxide synthase expression in articular chondrocytes through nuclear factor- B impairment
Authors: P. Richette, M.-F. Dumontier, K. Tahiri, M. Widerak, A. Torre, M. Benallaloua, F. Rannou, M.-T. Corvol, J.-F. Savouret
Journal: Annals of the Rheumatic Diseases (2006)

To investigate the presence and functionality of oestrogen receptor alpha (ERalpha) in interleukin (IL)1beta-treated rabbit articular chondrocytes in culture, and to determine the mechanisms of 17beta oestradiol (E2) effects on IL1beta-induced inducible nitric oxide synthase (iNOS) expression.The presence and functionality of ERalpha were investigated by immunocytochemistry and transient expression of an E2-responsive reporter construct. iNOS expression and production were determined by transient expression of a chimeric iNOS promoter-luciferase construct and protein immunoblotting. Nitric oxide (NO) production was determined by the Griess reaction. DNA-binding activities of nuclear factor-kappaB (NF-kappaB) and activated protein 1 were determined by electrophoretic mobility shift assay (EMSA)-ELISA assays. Nuclear translocation of p65 was studied by immunocytochemistry.ERalpha was identified in the nucleus of chondrocytes. ERalpha efficiently transactivated a transiently expressed E2-responsive construct. On IL1beta treatment, ERalpha partially diffused from its nuclear localisation into the cytoplasm and its transactivation ability was impaired. Nevertheless, E2, tamoxifen and raloxifene efficiently inhibited IL1beta-induced NO production (-34%, -31% and -36%, respectively). E2 decreased IL1beta-induced iNOS protein expression (-40%). Transient expression of an iNOS promoter construct strongly suggested that iNOS expression was inhibited at the transcriptional level, and EMSA-ELISA assays showed that E2 reduced (-60%) the IL1beta-induced p65 DNA-binding capacity. Finally, the p65 nuclear translocation induced by IL1beta was also strongly decreased by E2.Our data support a reciprocal antagonism between oestrogens and IL1beta, ultimately resulting in the decrease of cytokine-dependent NO production through transcriptional inhibition of iNOS expression. This effect was associated with selective inhibition of p65 DNA binding and nuclear translocation.
Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement
Authors: George D. Dangas, Thierry Lefèvre, Christian Kupatt, Didier Tchetche, Ulrich Schäfer, Nicolas Dumonteil, John G. Webb, Antonio Colombo, Stephan Windecker, Jurriën M. ten Berg, David Hildick-Smith, Roxana Mehran, Peter Boekstegers, Axel Linke, Christophe Tron, Eric Van Belle, Anita W. Asgar, Andreas Fach, Raban Jeger, Gennaro Sardella, Hans Ulrich Hink, Oliver Husser, Eberhard Grube, Efthymios N. Deliargyris, Ilknur Lechthaler, Debra Bernstein, Peter Wijngaard, Prodromos Anthopoulos, Christian Hengstenberg
Journal: Journal of the American College of Cardiology (2015)
Vitamin E Regulatory Mechanisms
Authors: Maret G. Traber
Journal: Annual Review of Nutrition (2007)

Dietary and supplemental vitamin E is absorbed and delivered to the liver, but of the various antioxidants with vitamin E activity, only alpha-tocopherol is preferentially recognized by the alpha-tocopherol transfer protein (alpha-TTP) and is transferred to plasma, while the other vitamin E forms (e.g., gamma-tocopherol or tocotrienols) are removed from the circulation. Hepatic alpha-TTP is required to maintain plasma and tissue alpha-tocopherol concentrations. The liver is the master regulator of the body's vitamin E levels in that it not only controls alpha-tocopherol concentrations, but also appears to be the major site of vitamin E metabolism and excretion. Vitamin Es are metabolized similarly to xenobiotics; they are initially omega-oxidized by cytochrome P450s, undergo several rounds of beta-oxidation, and then are conjugated and excreted. As a result of these various mechanisms, liver alpha-tocopherol and other vitamin E concentrations are closely regulated; thus, any potential adverse vitamin E effects are limited.
Role of Age and Health in Treatment Recommendations for Older Adults With Breast Cancer: The Perspective of Oncologists and Primary Care Providers
Authors: Arti Hurria, F. Lennie Wong, Doojduen Villaluna, Smita Bhatia, Cathie T. Chung, Joanne Mortimer, Sara Hurvitz, Arash Naeim
Journal: Journal of Clinical Oncology (2008)

To determine the impact of age and health status on adjuvant treatment recommendations for older patients with breast cancer from the perspective of medical oncologists and primary care physicians with geriatric expertise.One hundred fifty-one oncologists and 158 primary care physicians with geriatric expertise participated in an online survey. The survey described hypothetical patients of varying ages (70, 75, 80, and 85 years) and health status (good, average, and poor) who had node-positive, hormone receptor-positive, human epidermal growth factor receptor 2 (HER-2)/neu-negative; and hormone receptor-negative, HER-2/neu-positive breast cancers. The effects of patient age and health status on the survey participants' adjuvant treatment recommendations were examined using generalized estimation equation methods.The majority of both oncologists and primary care physicians recommended some form of adjuvant therapy for patients of all ages (70, 75, 80, and 85 years) and health status. Both oncologists and primary care providers were less likely to recommend adjuvant treatment as a patient's age increased or health status declined (P < .0001). There were no significant differences in treatment recommendations among primary care physicians and oncologists for patients with hormone receptor-negative, HER-2/neu-positive tumors (P = .54). However, primary care providers were more likely than oncologists to recommend no adjuvant treatment for patients age 75 years or older with hormone receptor-positive, HER-2/neu-negative tumors (P < .01).Age and health status influence oncologists' and primary care providers' adjuvant treatment recommendations. Evidence-based guidelines for breast cancer treatment in older adults taking into account age and health status are needed.
Severity of Nonalcoholic Fatty Liver Disease and Progression to Cirrhosis Are Associated With Atherogenic Lipoprotein Profile
Authors: Mohammad S. Siddiqui, Michael Fuchs, Michael O. Idowu, Velimir A. Luketic, Sherry Boyett, Carol Sargeant, Richard T. Stravitz, Puneet Puri, Scott Matherly, Richard K. Sterling, Melissa Contos, Arun J. Sanyal
Journal: Clinical Gastroenterology and Hepatology (2014)
Testing the Neutral Fixation of Hetero-Oligomerism in the Archaeal Chaperonin CCT
Authors: Valentin Ruano-Rubio, Mario A. Fares
Journal: Molecular Biology and Evolution (2007)

The evolutionary transition from homo-oligomerism to hetero-oligomerism in multimeric proteins and its contribution to function innovation and organism complexity remain to be investigated. Here, we undertake the challenge of contributing to this theoretical ground by investigating the hetero-oligomerism in the molecular chaperonin cytosolic chaperonin containing tailless complex polypeptide 1 (CCT) from archaea. CCT is amenable to this study because, in contrast to eukaryotic CCTs where sub-functionalization after gene duplication has been taken to completion, archaeal CCTs present no evidence for subunit functional specialization. Our analyses yield additional information to previous reports on archaeal CCT paralogy by identifying new duplication events. Analyses of selective constraints show that amino acid sites from 1 subunit have fixed slightly deleterious mutations at inter-subunit interfaces after gene duplication. These mutations have been followed by compensatory mutations in nearby regions of the same subunit and in the interface contact regions of its paralogous subunit. The strong selective constraints in these regions after speciation support the evolutionary entrapment of CCTs as hetero-oligomers. In addition, our results unveil different evolutionary dynamics depending on the degree of CCT hetero-oligomerism. Archaeal CCT protein complexes comprising 3 distinct classes of subunits present 2 evolutionary processes. First, slightly deleterious and compensatory mutations were fixed neutrally at inter-subunit regions. Second, sub-functionalization may have occurred at substrate-binding and adenosine triphosphate–binding regions after the 2nd gene duplication event took place. CCTs with 2 distinct types of subunits did not present evidence of sub-functionalization. Our results provide the 1st in silico evidence for the neutral fixation of hetero-oligomerism in archaeal CCTs and provide information on the evolution of hetero-oligomerism toward sub-functionalization in archaeal CCTs.
The Genetic Revolution: Despite Perfection of Elegant Techniques, Ethical Answers Still Elusive
Authors: Rebecca Voelker
Journal: JAMA (1993)

AFTER DECADES of perfecting ways to locate genes on the chromosomes, determine their functions, and screen for their deleterious or beneficial effects, the nation's biomedical elite want to ensure that they really know how to use these elegant techniques. Many of the questions they grapple with have little to do with whether a five-gene therapy protocol will yield optimum treatment for patients with cystic fibrosis or if the study of gene sequences in yeast, worms, and flies eventually will fill in all the knowledge gaps about our own. Pure science is producing many of those answers. Less clear-cut are the implications of informed consent if newborn multiplex testing—which can detect hundreds of genetic diseases—becomes widespread. Or the ethical impact and emotional toll of screening for diseases for which there is no effective cure. Experts say few physicians have the know-how to begin screening and counseling for genetic illnesses, and the
In-Depth Proteomics to Define the Cell Surface and Secretome of Ovarian Cancer Cells and Processes of Protein Shedding
Authors: Vitor M. Faça, Samir M. Hanash
Journal: Cancer Research (2009)

Current proteomics technologies allow substantial depth of analysis of cellular and subcellular proteomes as shown in the proteomic profiling of ovarian cancer cells. This in-depth analysis has elucidated the repertoire of proteins expressed on the cell surface and proteins released into the extracellular milieu, uncovering extensive shedding of extracellular domains of cell adhesion proteins and a highly dynamic protein secretion process. The protein sets identified provide a rich resource of potential circulating markers and targets for imaging and therapeutics for ovarian cancer.