tbuckley/cabot-search huggingface dataset:
REACTIVITIES OF ANTIBODIES TO HIV AND SIV IN HUMAN SERA IN KENYA, GABON, AND GHANA
Authors: T Masuda, H Tsujimoto, Y Ohta, K Ishikawa, M Hayami, E.M Ocheng, B.K Johnson, P.M Tukei, E Delaporte, R.W Cooper, E Frost, J.A.A Mingle, M Osei-Kwasi
Journal: The Lancet (1988)
Wrestling With the High Price of Cancer Care: Should We Control Costs by Individuals' Ability to Pay or Society's Willingness to Pay?
Authors: Jennifer L. Malin
Journal: Journal of Clinical Oncology (2010)

microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 20:1043-1048, 2002 8. Lanza G, Gafa R, Santini A, et al: Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol 24:2359-2367, 2006 9. Kakar S, Aksoy S, Burgart LJ, et al: Mucinous carcinoma of the colon: Correlation of loss of mismatch repair enzymes with clinicopathologic features and survival. Mod Pathol 17:696-700, 2004 10. Popat S, Hubner R, Houlston RS: Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 23:609-618, 2005 11. Elsaleh H, Joseph D, Grieu F, et al: Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355: 1745-1750, 2000 12. Sargent D, Marsoni S, Monges G, et al: Defective mismatch repair as a predictive marker for lack of efficacy of FU-based adjuvant therapy in colon cancer. J Clin Oncol 28:3219-3227, 2010 13. Ribic CM, Sargent DJ, Moore MJ, et al: Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247-257, 2003 14. QUASAR Collaborative Group, Gray R, Barnwell J, et al: Adjuvant chemotherapy versus observation in patients with colorectal cancer: A randomised study. Lancet 370:2020-2029, 2007 15. Roth AD, Tejpar S, Yan P, et al: Correlation of molecular markers in colon cancer with stage-specific prognosis: Results of the translational study on the PETACC3 – EORTC 40993-SAKK 60-00 trial. Presented at the ASCO GI Cancer Symposium, San Francisco, CA, January 15-17, 2009 (abstr 288) 16. Kerr D, Gray R, Quirke P, et al: A quantitative multigene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in four large studies and results of the independent, prospectively designed QUASAR validation study. J Clin Oncol 27:15s, 2009 (suppl; abstr 4000)
Orphan Worm Finds a Home: Buddenbrockia is a Myxozoan
Authors: Ana Sara Monteiro, Beth Okamura, Peter W. H. Holland
Journal: Molecular Biology and Evolution (2002)

The strange wormlike Buddenbrockia plumatellae and the spore-forming myxozoans are among the most enigmatic animals known to science. Dumortier and van Beneden (1850) first noted worm-shaped parasites inside freshwater bryozoan colonies; these animals were later described by Schroder (1910, 1912) and named B. plumatellae (fig. 1). This species is almost unique in never having been confidently assigned to an animal phylum, nor has a monotypic phylum been erected for it. Indeed, Nielsen (1995, p. 437) lists Buddenbrockia as one of the last ‘‘five enigmatic taxa.’’ The vermiform shape and the presence of four longitudinal muscle blocks clearly suggest a placement within the Bilateria, perhaps related to nematodes, although it should be noted that Buddenbrockia has neither a gut nor a clear central nervous system. Myxozoans, in contrast, form plasmodia or hollow sacs in which infective spores are produced. The spores attach to new hosts using penetrative filaments everted from characteristic polar capsules. Because of their anatomical simplicity, myxozoans were long placed within the protists, but rDNA and Hox gene sequences now indicate they are metazoans (Smothers et al. 1994; Anderson, Canning, and Okamura 1998). The precise phylogenetic placement of Myxozoa within the Metazoa is controversial. If polar capsules are homologues of nematocysts, this character argues for common ancestry with Cnidaria. Such a placement was supported by a combined analysis of rDNA and morphological data (Siddall et al. 1995), although several other rDNA analyses have not supported this phylogenetic position (Smothers et al. 1994; Schlegel et al. 1996; Kim, Kim, and Cunningham 1999). In addition, myxozoans have been shown to possess central class Hox genes which is thought to be a uniquely bilaterian character (Anderson, Canning, and Okamura 1998; Ferrier and Holland 2001). Here, we report 18S rDNA sequences of B. plumatellae from three widely separate geographical locations and demonstrate near identity with the previously reported 18S rDNA of the myxozoan Tetracapsula bryozoides. We conclude that Buddenbrockia is a myxozoan, a contention also made recently from ultrastructural studies (Okamura et al. 2002). We suggest that some species of Myxozoa have two alternative morphological forms, occurring as motile worms and as sporeforming sacs. Furthermore, the anatomy of Buddenbrockia provides strong support for the bilaterian affinities of the Myxozoa.
Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism
Authors: Erin E. McClelland, André M. Nicola, Rafael Prados-Rosales, Arturo Casadevall
Journal: Journal of Clinical Investigation (2010)

Abs facilitate humoral immunity via the classical mechanisms of opsonization, complement activation, Ab-dependent cellular cytotoxicity, and toxin/viral neutralization. There is also evidence that some Abs mediate direct antimicrobial effects. For example, Ab binding to the polysaccharide capsule of the human pathogenic fungus Cryptococcus neoformans promotes opsonization but also inhibits polysaccharide release and biofilm formation. To investigate whether Ab binding affects C. neoformans directly, we analyzed fungal gene expression after binding of protective and nonprotective mAbs. The 2 IgM Abs and 1 IgG1 Ab tested each induced different changes in gene expression. The protective IgG1 mAb upregulated genes encoding proteins involved in fatty acid synthesis, the protective IgM mAb downregulated genes encoding proteins required for protein translation, and the nonprotective IgM mAb had modest effects on gene expression. Differences in gene expression correlated with mAb binding to different locations of the capsule. Of the 3 Abs tested, the protective IgG1 mAb bound to C. neoformans closest to the cell wall, produced specific differences in the pattern of phosphorylated proteins, caused changes in lipid metabolism, and resulted in increased susceptibility to the antifungal drug amphotericin B. These results suggest what we believe to be a new mode of action for Ab-mediated immunity and raise the possibility that immunoglobulins mediate cross talk between microbes and hosts through their effects on microbial metabolism.
Why rational norms are indispensable
Authors: Ulrike Hahn
Journal: Behavioral and Brain Sciences (2011)

Abstract Normative theories provide essential tools for understanding behaviour, not just for reasoning, judgement, and decision-making, but many other areas of cognition as well; and their utility extends to the development of process theories. Furthermore, the way these tools are used has nothing to do with the is-ought fallacy. There therefore seems no basis for the claim that research would be better off without them.
Significance of increased `splenic uptake' on liver scintiscanning
Authors: A. L. W. F. Eddleston, L. M. Blendis, S. B. Osborn, R. Williams
Journal: Gut (1969)

Peak activity over the spleen as a percentage of peak activity over the liver was measured in 265 <sup>99m</sup>Technetium sulphur colloid liver scintiscans. The value exceeded 70% in 50 cases. In 32 of these cirrhosis was present; the other 18 scans were from patients with a wide variety of conditions, including secondary deposits, hepatitis, and diseases involving the reticuloendothelial system. A measure of the total activity in the spleen was derived from the peak activity and the length of the spleen. In cirrhosis this was closely related to the finding of oesophageal varices thus showing the importance of a collateral circulation (which allows colloid to bypass the liver) in the increased uptake of colloid by the spleen. In eight patients with hepatosplenomegaly due to blood dyscrasia or disease involving the reticuloendothelial system, total activities in the liver and spleen were estimated from the anteroposterior colour dot scan, and both liver and spleen blood flow were measured by methods independent of reticuloendothelial cell function. The results showed that the main factor causing increased uptake of colloid by the spleen in these diseases was an increased blood flow in the spleen relative to that in the liver.
ADALIMUMAB IN THE MAINTENANCE OF REMISSION FOR INFLAMMATORY BOWEL DISEASE: NEED FOR WEIGHT-BASED DOSING?
Authors: G Chan, H Martin, R Farrell
Journal: Gut (2013)

<h3>Introduction</h3> In inflammatory bowel disease (IBD), administration of adalimumab (ADA), unlike infliximab, is not weight based. Historically, patients with severe IBD, particularly CD are emaciated and typically have low body weight. Since the advent of biologic therapy, patients are started with aggressive therapy at an earlier stage of disease and most IBD patients are now of a normal or high body mass index (BMI). Epidemiological studies have demonstrated that the BMI of IBD patients have gradually increased over time. However, the impact of patient9s weight on response to ADA is not known. <h3>Aims/Background</h3> To evaluate the impact of patient9s weight on the efficacy of ADA in maintaining remission in IBD. <h3>Method</h3> All patients with IBD who received ADA were recruited retrospectively. Patients9 weights prior to onset of ADA therapy were retrieved from file. Patients who did not achieve induction of remission with ADA were excluded. Remission was defined as a consistent Harvey Bradshaw score &lt;5 for CD and Mayo score &lt;/=2 for UC. Treatment failure was defined as requiring escalation of therapy or surgical intervention. <h3>Results</h3> 7.4% of patients (43/585) with IBD (31 CD, 12 UC) received ADA. Of these, 6/43 (14.0%) patients were primary non responders while 3/43 (7.0%) patients discontinued therapy due to side effects. Both these groups were excluded. In the 34 patients who responded to ADA, there were equal numbers of male and female patients, with a mean age at diagnosis of 29.7±12.1 years. The mean duration of ADA therapy was 25.4 months. Of those who initially responded to ADA, 11/34 (32.4%) subsequently required escalation of therapy in the form of reduced dosing interval (7/11), short term corticosteroid therapy (3/11) or surgical intervention (1/11). These patients who failed standard ADA therapy had a higher mean body weight of 79.6 kg compared to 70.7kg in those who were successfully maintained in remission with fortnightly ADA, p=0.126. <h3>Conclusion</h3> Despite the higher mean body weight in IBD patients who fail ADA therapy compared to those who respond, the result did not achieve statistical significance. However, the study did demonstrate a trend towards treatment failure in patients with a higher mean body weight and would indicate that we should consider weight based adalimumab dosing. Other similar factors that may influence the need for weight based dosing include patients9 BMI and abdominal girth.
Dose-Modified Oral Chemotherapy in the Treatment of AIDS-Related Non-Hodgkin's Lymphoma in East Africa
Authors: Walter O. Mwanda, Jackson Orem, Pingfu Fu, Cecilia Banura, Joweria Kakembo, Caren Auma Onyango, Anne Ness, Sherrie Reynolds, John L. Johnson, Vivek Subbiah, Jacob Bako, Henry Wabinga, Fatuma K. Abdallah, Howard J. Meyerson, Christopher C. Whalen, Michael M. Lederman, Jodi Black, Leona W. Ayers, Edward Katongole-Mbidde, Scot C. Remick
Journal: Journal of Clinical Oncology (2009)

PURPOSE Africa is burdened by the AIDS epidemic and attendant increase in HIV/AIDS-related malignancies. Pragmatic approaches to therapeutic intervention could be of great value. Dose-modified oral chemotherapy for AIDS-related non-Hodgkin's lymphoma is one such approach. PATIENTS AND METHODS The oral regimen consisted of lomustine 50 mg/m(2) on day 1 (cycle 1 only), etoposide 100 mg/m(2) on days 1 to 3, and cyclophosphamide/procarbazine 50 mg/m(2) each on days 22 to 26 at 6-week intervals (one cycle) for two total cycles in HIV-infected patients with biopsy-proven non-Hodgkin's lymphoma. Results Forty-nine patients (21 in Uganda and 28 in Kenya) were treated. The majority of patients were female (59%) and had a poor performance status (63%); 69% of patients had advanced-stage disease; and 18 patients (37%) had access to antiretroviral therapy. In total, 79.5 cycles of therapy were administered. The regimen was well tolerated, had modest effects (decline) on CD4(+) lymphocyte counts (P = .077), and had negligible effects on HIV-1 viral replication. Four febrile neutropenia episodes and three treatment-related deaths (6% mortality rate) occurred. The overall objective response rate was 78% (95% CI, 62% to 88%); median follow-up time was 8.2 months (range, 0.1 to 71 months); median event-free and overall survival times were 7.9 months (95% CI, 3.3 to 13.0 months) and 12.3 months (95% CI, 4.9 to 32.4 months), respectively; and 33% of patients survived 5 years. CONCLUSION Dose-modified oral chemotherapy is efficacious, has comparable outcome to that in the United States in the pre-highly active antiretroviral therapy setting, has an acceptable safety profile, and is pragmatic in sub-Saharan Africa. The international collaboration has been highly successful, and subsequent projects should focus on strategies to optimize combination antiretroviral therapy and chemotherapy and follow-up tissue correlative studies.
Targeting the vascular endothelial growth factor system to prevent ovarian hyperstimulation syndrome
Authors: S. R. Soares, R. Gomez, C. Simon, J. A. Garcia-Velasco, A. Pellicer
Journal: Human Reproduction Update (2008)

Ovarian hyperstimulation syndrome (OHSS) typically occurs when ovaries are primed with FSH/LH and subsequently exposed to hCG. The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). A search of the literature was carried out using PubMed and the authors' files. In rodents and humans, the expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases during ovarian stimulation. With the administration of hCG, the expression of each rises to a maximum. Expression of VEGF/VEGFR-2 mRNAs correlates with enhanced VP, with both peaking 48 h following an injection of hCG. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. Increased VP may be mediated through adhesion molecules such as VE-cadherin, which is involved in the loosening of endothelial intercellular junctions. These findings regarding the pathophysiology of OHSS suggest that the syndrome can be prevented by inducing ovulation with LH or GnRH analogues, which prevent VEGF overexpression. Also, co-administration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo (P = 0.04). The pathophysiological mechanisms involved in OHSS suggest potential preventive approaches, but larger trials are necessary for evaluating the efficacy and safety of the pharmaco-prevention of OHSS.
Complications of Evans' syndrome in an infant with hereditary spherocytosis: a case report
Authors: Hideki Yoshida, Hiroyuki Ishida, Takao Yoshihara, Takashi Oyamada, Masataka Kuwana, Toshihiko Imamura, Akira Morimoto
Journal: Journal of Hematology & Oncology (2009)

Hereditary spherocytosis (HS) is a genetic disorder of the red blood cell membrane clinically characterized by anemia, jaundice and splenomegaly. Evans' syndrome is a clinical syndrome characterized by autoimmune hemolytic anemia (AIHA) accompanied by immune thrombocytopenic purpura (ITP). It results from a malfunction of the immune system that produces multiple autoantibodies targeting at least red blood cells and platelets. HS and Evans' syndrome have different mechanisms of pathophysiology one another. We reported the quite rare case of an infant who had these diseases concurrently. Possible explanations of the unexpected complication are discussed.
Logic in medicine: an economic perspective.
Authors: A Maynard
Journal: BMJ (1987)

The Concise Oxford Dictionary defines logic as   of thinking or a chain of reasoning or thought defensible on  grounds of consistency. Economics, at its best, is a logical way of analysing  costs and benefits of alternative ways of achieving competing objectives: it is   of deciding how to allocate scarce means among competing ends. Thomas Carlyle argued that economics was not a gay science but the dismal science. Carlyle reached this conclusion because  basic assumptions of economics are scarcity and  ubiquitous necessity to make choices. In health care these factors require  allocators of resources to decide who will die and who will live in what degree of pain and discomfort.
Relationship Between Instantaneous Aortic Flow and the Pressure Gradient
Authors: JOSEPH C. GREENFIELD, DONALD L. FRY
Journal: Circulation Research (1965)

The relationship between the pressure gradient and the instantaneous blood flow in the descending thoracic aorta was studied in six dogs. Instantaneous flow was calculated from the pressure gradient using the simple analog approach of Fry and the more elaborate calculations of Womersley. The flows computed by either of these techniques were essentially indistinguishable from one another and compared favorably with the "true" flow. The "true" flow at the point of pressure gradient measurement was determined indirectly from the flow signals of two electromagnetic flowmetering systems, one placed upstream and the other downstream from the point of pressure gradient measurement. The probes were placed sufficient distances from the site at which pressure gradients were measured so that the pulsations of the vessel at that site were unaffected by application and removal of the probes. Thus, the vessel was presumed to be in its normal pulsating state. It is concluded, first, that the simpler approach of Fry is the method of choice in large vessels such as the aorta because the results do not differ appreciably from those using the Womersley approach. Second, the favorable comparison of either of the pressure gradient techniques with the "true" flow is strong evidence for the validity of this method and places the theoretical considerations of Womersley and others on a firmer experimental footing than previously.
Three cases of childhood nocturnal asthma due to buckwheat allergy
Authors: S. Y. Lee, K. S. Lee, C. H. Hong, K. Y. Lee
Journal: Allergy (2001)

Background: Buckwheat flour (BF) is known as a potent food allergen. Sensitization to it usually occurs by ingestion but also by inhalation in occupational or domestic exposure. Buckwheat chaff‐stuffed pillows (BCP) can be contaminated with BF during the process of pilling, and many Korean children and adults use BCP for health reasons. Methods and Results: We here present three cases of BF allergy in children using BCP, who had been treated as nonatopic asthmatics after undergoing the routine allergy skin tests and serologic tests. We took careful clinical histories, and performed skin prick tests (SPT), the radioimmunoassay (RIA) for specific IgE, the BCP‐elimination test, the BF bronchial provocation test, and IgE Western blot. All three children showed positive skin reactions to BF, but none of them had positive reactions to house‐dust mites. Nocturnal asthmatic symptoms were improved during 7 days of BCP elimination, and asthmatic responses were observed by bronchial provocation tests with homemade BF extract. Serum BF‐specific IgE antibodies and several IgE‐binding proteins were detected by RIA and Western blot analysis, respectively. Conclusions: Thus, a small amount of BF attached to BCP can induce BF sensitization, and BCP should be considered a main cause of childhood nocturnal asthma in those asthmatics exposed to these pillows.
Phase II Study of the Cyclin-Dependent Kinase Inhibitor Flavopiridol Administered to Patients With Advanced Gastric Carcinoma
Authors: Gary K. Schwartz, David Ilson, Leonard Saltz, Eileen O’Reilly, William Tong, Peter Maslak, Jeanine Werner, Pam Perkins, Maxine Stoltz, David Kelsen
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Flavopiridol is the first cyclin-dependent kinase inhibitor to enter clinical trials. Activity in gastric cancer xenografts and in a patient with gastric cancer on the phase I trial led to this phase II study of flavopiridol in patients with metastatic gastric cancer. PATIENTS AND METHODS: Sixteen patients were entered onto the study, and 14 were assessable for response. Flavopiridol was administered initially at a dose of 50 mg/m 2 /d by continuous infusion for 72 hours every 2 weeks. Assessment of plasma pharmacokinetics was performed in all patients. Peripheral mononuclear cells were collected throughout the 72-hour infusion for determinants of apoptosis. RESULTS: There were no major objective responses (exact confidence interval 0% to 23%). One patient achieved a minor response in his liver metastases, though the primary progressed. Other patients exhibited histologic and radiographic evidence of tumor necrosis. Common toxicities included fatigue in 93% of patients (grade 3 or 4 in 27%) and diarrhea in 73% of patients (grade 3 or 4 in 20%). Five patients (33%) developed venous thromboses at the central catheter tip. The studies performed on peripheral mononuclear cells indicated no induction of apoptosis. CONCLUSION: Flavopiridol administered as a single agent for 72 hours every 14 days is inactive in the treatment of gastric cancer. The drug also induced an unexpected higher incidence of vascular thrombosis and fatigue than was anticipated from the phase I trials. Future development of flavopiridolwill depend on other doses and schedules in combination with chemotherapy.
The XYY Genotype
Authors: S Walzer, P S Gerald, S A Shah
Journal: Annual Review of Medicine (1978)

The epidemiological data pertaining to the XYY genotype suggest that there is a three- to fourfold overrepresentation of XYY individuals in mental and penal settings and a twentyfold overrepresentation of mental-penal (special security) settings. The reasons behind the risk for behavioral disability are not known at this time. Tallness and ondulocystic acne are reported frequently to be associated with the genotype. Since much of the available information about the XYY sex chromosome complement is biased, more data is required before definitive statements can be made about the personality characteristics or intelligence of the vast majority of XYY men not appearing in social settings oriented towards behavioral deviancy.