tbuckley/cabot-search huggingface dataset:
Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants
Authors: Salim Abdulla, Rolf Oberholzer, Omar Juma, Sulende Kubhoja, Francisca Machera, Christopher Membi, Said Omari, Alwisa Urassa, Hassan Mshinda, Ajuza Jumanne, Nahya Salim, Mwanjaa Shomari, Thomas Aebi, David M. Schellenberg, Terrell Carter, Tonya Villafana, Marie-Ange Demoitié, Marie-Claude Dubois, Amanda Leach, Marc Lievens, Johan Vekemans, Joe Cohen, W. Ripley Ballou, Marcel Tanner
Journal: New England Journal of Medicine (2008)

The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants.In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives.At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P=0.01).The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. (ClinicalTrials.gov number, NCT00289185.)
Risk of Pelvic Fractures in Older Women Following Pelvic Irradiation
Authors: Nancy N. Baxter, Elizabeth B. Habermann, Joel E. Tepper, Sara B. Durham, Beth A. Virnig
Journal: JAMA (2005)

Context Pelvic fractures, including hip fractures, are a major source of morbidity and mortality in older women.Although therapeutic pelvic irradiation could increase the risk of such fractures, this effect has not been studied. ObjectiveTo determine if women who undergo pelvic irradiation for pelvic malignancies (anal, cervical, or rectal cancers) have a higher rate of pelvic fracture than women with pelvic malignancies who do not undergo irradiation. Design, Setting, and ParticipantsWe conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims data.A total of 6428 women aged 65 years and older diagnosed with pelvic malignancies from 1986 through 1999 were included.We compared results for women who did (n = 2855) vs did not (n = 3573) undergo radiation therapy.To assess the influence of selection bias, we also evaluated the effect of irradiation on osteoporotic fractures in nonirradiated sites (arm and spine). Main Outcome MeasureWe evaluated the effect of irradiation on the incidence of pelvic fractures over time, and adjusted for potential confounders using a proportional hazards model. ResultsWomen who underwent radiation therapy were more likely to have a pelvic fracture than women who did not undergo radiation therapy (cumulative 5-year fracture rate, 14.0% vs 7.5% in women with anal cancer, 8.2% vs 5.9% in women with cervical cancer, and 11.2% vs 8.7% in women with rectal cancer); the difference was statistically significant and most fractures (90%) were hip fractures.We controlled for potential confounders including age, race, cancer stage, and geographic location.The impact of irradiation varied by cancer site: treatment for anal cancer was associated with a higher risk of pelvic fractures (hazard ratio, 3.16; 95% confidence interval, 1.48-6.73);than for cervical cancer (hazard ratio, 1.66; 95% confidence interval, 1.06-2.59);or rectal cancer (hazard ratio, 1.65; 95% confidence interval, 1.33-2.05).No statistically significant difference was found in the rate of arm or spine fractures between the irradiated and nonirradiated groups (hazard ratio, 1.15; 95% confidence interval, 0.89-1.48).Conclusions Pelvic irradiation substantially increases the risk of pelvic fractures in older women.Given the high baseline risk of pelvic fracture, this finding is of particular concern.
Thromboembolic risk among Danish children and adults with inflammatory bowel diseases: a population-based nationwide study
Authors: M. D. Kappelman, E. Horvath-Puho, R. S. Sandler, D. T. Rubin, T. A. Ullman, L. Pedersen, J. A. Baron, H. T. Sorensen
Journal: Gut (2011)

Clonidine and ICI 106270 are centrally acting antihypertensive agents which act through stimulation of medullary alpha-2 adrenoceptors. Both compounds are equipotent agonists at alpha-2 adrenoceptors as assessed in functional studies in isolated organs and in radioligand binding studies. In addition, clonidine and ICI 106270 possess the same degree of selectivity for alpha-2 adrenoceptors over alpha-1 adrenoceptors. Clonidine and ICI 106270 are equipotent antihypertensive agents after intracisternal administration to spontaneously hypertensive rats, consistent with the observations made in vitro that both compounds are equipotent alpha-2 adrenoceptor agonists. Both compounds were less potent in lowering blood pressure after i.v. administration than after intracisternal administration, thus confirming a central mechanism of action. Interestingly, clonidine was a more potent antihypertensive agent than ICI 106270 after i.v. administration, which, in view of the equal potencies observed after intracisternal administration, suggests that diffusion of ICI 106270 into the central nervous system is selectively retarded, relative to clonidine, by the blood-brain barrier. The differences observed in the rate of penetration of the blood-brain barrier are consistent with the higher pka and corresponding higher extent of ionization (at physiological pH) and lower lipophilicity of ICI 106270 relative to clonidine. A relatively large difference between the i.v. and p.o. antihypertensive potencies was observed for ICI 106270 which indicates poor p.o. absorption of ICI 106270 relative to clonidine, again likely resulting from the greater proportion of ICI 106270 existing in the ionized species.(ABSTRACT TRUNCATED AT 250 WORDS)
TYROSINE KINASE INHIBITORS AND THE DAWN OF MOLECULAR CANCER THERAPEUTICS
Authors: Raoul Tibes, Jonathan Trent, Razelle Kurzrock
Journal: The Annual Review of Pharmacology and Toxicology (2004)

▪ Abstract The clinical application of tyrosine kinase inhibitors for cancer treatment represents a therapeutic breakthrough. The rationale for developing these compounds rests on the observation that tyrosine kinase enzymes are critical components of the cellular signaling apparatus and are regularly mutated or otherwise deregulated in human malignancies. Novel tyrosine kinase inhibitors are designed to exploit the molecular differences between tumor cells and normal tissues. Herein, we will review the current state-of-the-art using agents that target as prototypes Bcr-Abl, platelet-derived growth factor receptor (PDGFR), KIT (stem cell factor receptor), and epidermal growth factor receptor (EGFR). These compounds are remarkably effective in treating diverse cancers that are highly resistant to conventional treatment, including various forms of leukemia, hypereosinophilic syndrome, mast cell disease, sarcomas, and lung cancer. It is now clear that the molecular defects underlying cancer can be targeted with designer drugs that yield striking salutary effects with minimal toxicity.
EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration
Authors: J. K. Field, T. Liloglou, A. Niaz, J. Bryan, J. R. Gosney, T. Giles, C. Brambilla, E. Brambilla, A. Vesin, J-F. Timsit, P. Hainaut, Y. Martinet, J. M. Vignaud, F. B. Thunnissen, C. Prinsen, P. J. Snijders, E. F. Smit, G. Sozzi, L. Roz, A. Risch, H. D. Becker, J. S. Elborn, N. D. Magee, L. M. Montuenga, M. J. Pajares, M. D. Lozano, K. J. O'Byrne, D. J. Harrison, J. Niklinski, A. Cassidy
Journal: European Respiratory Journal (2009)

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular–pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARβ genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes.
How accurate are the Swansea criteria to diagnose acute fatty liver of pregnancy in predicting hepatic microvesicular steatosis?
Authors: A. Goel, B. Ramakrishna, U. Zachariah, J. Ramachandran, C. E. Eapen, G. Kurian, G. Chandy
Journal: Gut (2010)

We noted that in two recent reports in Gut , none of 62 patients diagnosed by the Swansea criteria to have acute fatty liver of pregnancy (AFLP) underwent liver biopsy.1 2 We retrospectively assessed the accuracy of the Swansea criteria to predict hepatic microvesicular steatosis in 34 patients with suspected pregnancy-related liver disease who underwent liver biopsy at our centre between 1998 and 2006. These patients tested negative for other causes of acute liver dysfunction such as hepatitis viruses (hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) antibody, immunoglobulin (Ig) M hepatitis A virus (HAV) antibody, IgM hepatitis E virus (HEV) antibody), malarial parasite and sepsis (blood culture). No patient gave a history of ingestion of a potentially hepatotoxic drug. We excluded 10 patients (details in figure 1).



Figure 1 
Flowchart of patients with suspected pregnancy-related liver disease who underwent liver …
Cancer Biomarkers Defined by Autoantibody Signatures to Aberrant O-Glycopeptide Epitopes
Authors: Hans H. Wandall, Ola Blixt, Mads A. Tarp, Johannes W. Pedersen, Eric P. Bennett, Ulla Mandel, Govind Ragupathi, Phil O. Livingston, Michael A. Hollingsworth, Joyce Taylor-Papadimitriou, Joy Burchell, Henrik Clausen
Journal: Cancer Research (2010)

Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we evaluated whether autoantibodies generated to aberrant O-glycoforms of MUC1 might serve as sensitive diagnostic biomarkers for cancer. Using an antibody-based glycoprofiling ELISA assay, we documented that aberrant truncated glycoforms were not detected in sera of cancer patients. An O-glycopeptide microarray was developed that detected IgG antibodies to aberrant O-glycopeptide epitopes in patients vaccinated with a keyhole limpet hemocyanin-conjugated truncated MUC1 peptide. We detected cancer-associated IgG autoantibodies in sera from breast, ovarian, and prostate cancer patients against different aberrent O-glycopeptide epitopes derived from MUC1. These autoantibodies represent a previously unaddressed source of sensitive biomarkers for early detection of cancer. The methods we have developed for chemoenzymatic synthesis of O-glycopeptides on microarrays may allow for broader mining of the entire cancer O-glycopeptidome.
Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial
Authors: Anne-Marie Wills, Jane Hubbard, Eric A Macklin, Jonathan Glass, Rup Tandan, Ericka P Simpson, Benjamin Brooks, Deborah Gelinas, Hiroshi Mitsumoto, Tahseen Mozaffar, Gregory P Hanes, Shafeeq S Ladha, Terry Heiman-Patterson, Jonathan Katz, Jau-Shin Lou, Katy Mahoney, Daniela Grasso, Robert Lawson, Hong Yu, Merit Cudkowicz
Journal: The Lancet (2014)
PLA<sub>2</sub>R Autoantibodies and PLA<sub>2</sub>R Glomerular Deposits in Membranous Nephropathy
Authors: Hanna Debiec, Pierre Ronco
Journal: New England Journal of Medicine (2011)

To the Editor: Membranous nephropathy is a common cause of the nephrotic syndrome in adults. Treatment is controversial and challenging because of the heterogeneity of the disease and a lack of reliable biomarkers.1,2 M-type phospholipase A2 receptor (PLA2R) was recently identified as a major target antigen involved in idiopathic membranous nephropathy in adults.3 Circulating autoantibodies against PLA2R were found in 70 to 80% of patients with idiopathic membranous nephropathy but not in those with secondary membranous nephropathy or other renal diseases. It has been suggested that the serum level of PLA2R autoantibody . . .
Hart of Glyncorrwg
Authors: R. Moorhead
Journal: Journal of the Royal Society of Medicine (2004)

Born in 1927, Julian Tudor Hart (Figure 1) grew up in a home that served, among other things, as a transit camp for anti-fascist refugees from Continental Europe. His mother, Dr Alison Macbeth, was a member of the Labour Party. His father, Dr Alexander Tudor Hart, belonged to the Communist Party and represented the South Wales Miners' Federation in a dispute over medical care; later he volunteered as a surgeon for the International Brigades fighting against General Franco in the Spanish Civil War. Despite the efforts of his parents to discourage him from entering medicine, Julian's ambition was to be a general practitioner in a coal mining community; but as a medical student in Cambridge and London he recognized the dismal reputation of general practice as the least satisfying and most frustrating field of medicine. If serious-minded students were to be turned to this kind of work, the intolerable features of general practice had to modified.1 New recruits to medicine, he argued, should cultivate disciplined anger against the attitudes and circumstances that impeded effective delivery of medical science to sick people.2 These and subsequent opinions were doubtless coloured by his Marxist convictions. Later in life he expanded on his critique of the medical profession, declaring that medical education was `training the wrong people, at the wrong time, in the wrong skills and in the wrong place'.3



Figure 1

Julian Tudor Hart, 1995 [Photograph by Nick Sinclair from the photograph collection of the National Portrait Gallery]



Hart graduated in 1952 and after hospital posts and experience in urban general practice he became involved in epidemiological research, first with Richard Doll and later with Archie Cochrane. At that time, the late 1950s, there was a growing perception that each general practice should be regarded as a population at risk4 and that general practitioners needed to couple their traditional curative medicine with the methods and techniques of the epidemiologist and the medical officer of health (in conjunction with colleagues in allied health professions). At the same time, four large changes were underway in medicine. First, the bioethics movement was encouraging patients and their families to share the overall responsibility for healthcare. Secondly, the family practice movement was emphasizing the holistic dimensions of healthcare, including lifestyle factors. Thirdly, the preventive medicine movement was starting to develop guidelines for practice.5 And, fourthly, the advent of new diuretics and sympathetic blocking agents was making the treatment of hypertension easier and freer from side-effects.6 In 1961 he moved to Glyncorrwg, South Wales, and set up a research practice.7
Ovarian Cancer Spheroids Use Myosin-Generated Force to Clear the Mesothelium
Authors: Marcin P. Iwanicki, Rachel A. Davidowitz, Mei Rosa Ng, Achim Besser, Taru Muranen, Melissa Merritt, Gaudenz Danuser, Tan Ince, Joan S. Brugge
Journal: Cancer Discovery (2011)

Dissemination of ovarian tumors involves the implantation of cancer spheroids into the mesothelial monolayer on the walls of peritoneal and pleural cavity organs. Biopsies of tumors attached to peritoneal organs show that mesothelial cells are not present under tumor masses. We have developed a live, image-based in vitro model in which interactions between tumor spheroids and mesothelial cells can be monitored in real time to provide spatial and temporal understanding of mesothelial clearance. Here we provide evidence that ovarian cancer spheroids utilize integrin- and talin- dependent activation of myosin and traction force to promote mesothelial cells displacement from underneath a tumor cell spheroid. These results suggest that ovarian tumor cell clusters gain access to the sub-mesothelial environment by exerting force on the mesothelial cells lining target organs, driving migration and clearance of the mesothelial cells.
Hypoglycemia Detection Rate Differs Among Blood Glucose Monitoring Sites
Authors: Shu Meguro, Osamu Funae, Kazuhiro Hosokawa, Yoshihito Atsumi
Journal: Diabetes Care (2005)

To achieve better glycemic control, self-monitoring of blood glucose (SMBG) plays an important role in diabetes management. Although fingertip capillary blood has been used for SMBG, alternative-site blood glucose testing (i.e., from the forearm or the palm of the hand) has been developed because patients have requested less painful measurement techniques. However, there has been debate about blood glucose equivalence at alternative sites because some reports suggest that glucose monitoring at the forearm shows a delayed value if blood glucose changes rapidly (1,2). One study reported that blood glucose measurement at the palm is not delayed compared with fingertip measurement after a test meal and exercise load (3). Another study reported that palm blood glucose is comparable to fingertip blood glucose in acute hypoglycemia (4). Since there has been no research comparing blood glucose values simultaneously at the fingertip, forearm, and palm of the hand in …
Mannitol Bronchoprovocation in the Evaluation of Airway Reactivity in a High-Risk Pediatric Cohort
Authors: A.Y. Okupa, D.J. Jackson, C.A. Sorkness, V.P. Rajamanickam, T.J. Kang, I.A. Awoyinka, E.L. Anderson, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2012)
Microparticles
Authors: Sebastian F. Mause, Christian Weber
Journal: Circulation Research (2010)

Microparticles represent a heterogeneous population of vesicles with a diameter of 100 to 1000 nm that are released by budding of the plasma membrane and express antigens specific of their parental cells. Although microparticle formation represents a physiological phenomenon, a multitude of pathologies are associated with a considerable increase in circulating microparticles, including inflammatory and autoimmune diseases, atherosclerosis, and malignancies. Microparticles display an broad spectrum of bioactive substances and receptors on their surface and harbor a concentrated set of cytokines, signaling proteins, mRNA, and microRNA. Recent studies provided evidence for the concept of microparticles as veritable vectors for the intercellular exchange of biological signals and information. Indeed, microparticles may transfer part of their components and content to selected target cells, thus mediating cell activation, phenotypic modification, and reprogramming of cell function. Because microparticles readily circulate in the vasculature, they may serve as shuttle modules and signaling transducers not only in their local environment but also at remarkable distance from their site of origin. Altogether, this transcellular delivery system may extend the confines of the limited transcriptome and proteome of recipient cells and establishes a communication network in which specific properties and information among cells can be efficiently shared. At least in same cases, the sequential steps of the transfer process underlie complex regulatory mechanisms, including selective sorting ("packaging") of microparticle components and content, specificity of interactions with target cells determined by surface receptors, and ultimately finely tuned and signal-dependent release and delivery of microparticle content.
Incidence of Hepatocellular Carcinoma Among US Patients With Cirrhosis of Viral or Nonviral Etiologies
Authors: Robert D. Mair, Antonia Valenzuela, Nghiem B. Ha, Walid S. Ayoub, Tami Daugherty, Glen A. Lutchman, Gabriel Garcia, Aijaz Ahmed, Mindie H. Nguyen
Journal: Clinical Gastroenterology and Hepatology (2012)

We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence.We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of α-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6-99 mo).The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan-Meier analysis (P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child-Pugh-Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3-10.1; P = .02) but Asian ethnicity was not.In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.