tbuckley/cabot-search huggingface dataset:
Occurrence of injuries and illnesses during the 2009 IAAF World Athletics Championships
Authors: Juan-Manuel Alonso, Philippe M Tscholl, Lars Engebretsen, Margo Mountjoy, Jiri Dvorak, Astrid Junge
Journal: British Journal of Sports Medicine (2010)

To analyse the frequency and characteristics of sports injuries and illnesses incurred during the World Athletics Championships.Prospective recording of newly occurred injuries and illnesses.Twelfth International Association of Athletics Federations World Championships in Athletics 2009 in Berlin, Germany.National team physicians and physiotherapists and 1979 accredited athletes; Local Organising Committee physicians working in the Medical Centres.Incidence and characteristics of newly incurred injuries and illnesses.236 injury incidents with 262 injured body parts and 269 different injury types were reported, representing an incidence of 135.4 injuries per 1000 registered athletes. Eighty percent affected the lower extremity. Thigh strain (13.8%) was the main diagnosis. Overuse (44.1%) was the predominant cause. Most injuries were incurred during competition (85.9%). About 43.8% of all injury events were expected to result in time-loss. 135 illnesses were reported, signifying an incidence of 68.2 per 1000 registered athletes. Upper respiratory tract infection was the most common condition (30.4%) and infection was the most frequent cause (32.6%). The incidence of injury and illnesses varied substantially among the events.The risk of injury varied with each discipline. Preventive measures should be specific and focused on minimising the potential for overuse. Attention should be paid to ensure adequate rehabilitation of previous injuries. The addition of the illness part to the injury surveillance system proved to be feasible. As most illnesses were caused by infection of the respiratory tract or were environmentally related, preventive interventions should focus on decreasing the risk of transmission, appropriate event scheduling and heat acclimatisation.
Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice.
Authors: B E Rich, J Campos-Torres, R I Tepper, R W Moreadith, P Leder
Journal: The Journal of Experimental Medicine (1993)

To investigate the role of interleukin 7 (IL-7) in the development of the lymphoid system, we have generated two lines of transgenic mice carrying an IL-7 cDNA fused to an immunoglobulin heavy chain promoter and enhancer. This transgene is expressed in the bone marrow, lymph nodes, spleen, thymus, and skin provoking a perturbation of T cell development characterized by a marked reduction of CD4+ CD8+ (double-positive) thymocytes. Quite unexpectedly, however, both lines also develop a progressive cutaneous disorder involving a dermal lymphoid infiltrate that results in progressive alopecia, hyperkeratosis, and exfoliation. Although the infiltrate is primarily composed of T lineage cells, its development is not impeded in the athymic nu/nu background. Furthermore, the phenotype can be transmitted horizontally by transplanting lymphoid tissues or skin to syngeneic wild-type mice. Thus, the phenotype is conveyed by skin-homing, mobile cells (presumably the infiltrating lymphocytes) in a cell-autonomous fashion. In addition to the skin phenotype, this transgene also provokes the development of a lymphoproliferative disorder that induces B and T cell lymphomas within the first 4 mo of life. These findings suggest potential physiologic actions of IL-7 in T cell development and in cutaneous immunity. They also demonstrate that IL-7 can act as an oncogene in the living organism.
Ascorbyl free radical as a real-time marker of free radical generation in briefly ischemic and reperfused hearts. An electron paramagnetic resonance study.
Authors: M K Sharma, G R Buettner, K T Spencer, R E Kerber
Journal: Circulation Research (1994)

The role of free radicals in myocardial reperfusion injury remains controversial. We have developed a new method using ascorbyl free radical (AFR) as a real-time, quantitative marker of free radical generation during myocardial reperfusion. A total of 35 dogs were studied. Twelve open-chest dogs underwent either 5 minutes (n = 5) or 20 minutes (n = 7) of coronary artery occlusion and 30 minutes of reperfusion. Seven additional animals undergoing 20 minutes of coronary occlusion also received the antioxidant enzymes superoxide dismutase and catalase, beginning 10 minutes before occlusion through the end of reperfusion. Exogenous ascorbate was infused intravenously, and the concentration of AFR in the great cardiac vein was continuously measured by electron paramagnetic resonance spectroscopy. Preocclusion AFR concentration was similar in the three groups. Upon reperfusion, AFR rose significantly in each animal group (P &lt; .05). However, the AFR rise in the 20-minute-occlusion group, 38 +/- 17%, was significantly greater than in the 5-minute-occlusion group, 27 +/- 14% (P &lt; .002). In addition, in the animals that received superoxide dismutase and catalase, the rise in the AFR was markedly attenuated, 13 +/- 6% (P &lt; .002). Two dogs that received ascorbate but did not undergo coronary artery occlusion/reperfusion sequences showed no change in coronary venous AFR signal, indicating the stability of the signal over time. Five dogs received ascorbate while undergoing interventions to alter coronary venous flow: intravenous saline, dobutamine, dipyridamole, and nitroglycerin. Coronary venous AFR changes were minimal despite large coronary flow alterations, indicating that the AFR signal is independent of changes in coronary venous flow.(ABSTRACT TRUNCATED AT 250 WORDS)
The Heat Shock Protein 90 Inhibitor, 17-Allylamino-17-demethoxygeldanamycin, Enhances Osteoclast Formation and Potentiates Bone Metastasis of a Human Breast Cancer Cell Line
Authors: John T. Price, Julian M.W. Quinn, Natalie A. Sims, Jessica Vieusseux, Kelly Waldeck, Susan E. Docherty, Damian Myers, Akira Nakamura, Mark C. Waltham, Matthew T. Gillespie, Erik W. Thompson
Journal: Cancer Research (2005)

Abstract Breast cancer metastasis to the bone occurs frequently, causing numerous complications including severe pain, fracture, hypercalcemia, and paralysis. Despite its prevalence and severity, few effective therapies exist. To address this, we examined whether the heat shock protein 90 (Hsp90) inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), would be efficacious in inhibiting breast cancer metastasis to bone. Utilizing the human breast cancer subline, MDA-MB-231SA, previously in vivo selected for its enhanced ability to generate osteolytic bone lesions, we determined that 17-AAG potently inhibited its in vitro proliferation and migration. Moreover, 17-AAG significantly reduced MDA-MB-231SA tumor growth in the mammary-fat pad of nude mice. Despite these findings, 17-AAG enhanced the incidence of bone metastasis and osteolytic lesions following intracardiac inoculation in the nude mouse. Consistent with these findings, 17-AAG enhanced osteoclast formation 2- to 4-fold in mouse bone marrow/osteoblast cocultures, receptor activator of nuclear factor κB ligand (RANKL)–stimulated bone marrow, and RAW264.7 cell models of in vitro osteoclastogenesis. Moreover, the drug enhanced osteoclastogenesis in human cord blood progenitor cells, demonstrating that its effects were not limited to mouse models. In addition to 17-AAG, other Hsp90 inhibitors, such as radicicol and herbimycin A, also enhanced osteoclastogenesis. A pro-osteolytic action of 17-AAG independent of tumor presence was also determined in vivo, in which 17-AAG–treated tumor-naïve mice had reduced trabecular bone volume with an associated increase in osteoclast number. Thus, HSP90 inhibitors can stimulate osteoclast formation, which may underlie the increased incidence of osteolysis and skeletal tumor incidence caused by 17-AAG in vivo. These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial.
Prevention and treatment of renal allograft rejection
Authors: C Y Lu, S C Sicher, M A Vazquez
Journal: Journal of the American Society of Nephrology (1993)

Renal transplantation is the preferred treatment modality for patients with ESRD who are good surgical risks and able to comply with chronic immunosuppressive medications. Clinical transplantation has advanced significantly, with most transplant centers reporting 1-yr renal allograft survival rates of better than 80%. Nevertheless, rejection and a progressive loss of allografts over time continue to occur. The immunosuppressive agents currently used may lead to the development of life-threatening infections, malignancies, and advanced atherosclerosis as a consequence of some of their side effects. This review examines the mechanisms involved in allograft rejection as currently understood. The recent knowledge into the mechanism of action of cyclosporine, FK506, and rapamycin on T cell activation is presented. Information recently available on some of the established therapies such as steroids, antimetabolites and monoclonal antibodies as well as the newer agents is also discussed. The interaction between clinical transplantation and basic research in immunology continues to result in exciting advances in both fields.
Inhibition of gastric inhibitory polypeptide signaling prevents obesity
Authors: Kazumasa Miyawaki, Yuichiro Yamada, Nobuhiro Ban, Yu Ihara, Katsushi Tsukiyama, Heying Zhou, Shimpei Fujimoto, Akira Oku, Kinsuke Tsuda, Shinya Toyokuni, Hiroshi Hiai, Wataru Mizunoya, Tohru Fushiki, Jens Juul Holst, Mitsuhiro Makino, Akira Tashita, Yukari Kobara, Yoshiharu Tsubamoto, Takayoshi Jinnouchi, Takahito Jomori, Yutaka Seino
Journal: Nature Medicine (2002)
Very young women (&lt;35 years) with operable breast cancer: features of disease at presentation
Authors: M. Colleoni, N. Rotmensz, C. Robertson, L. Orlando, G. Viale, G. Renne, A. Luini, P. Veronesi, M. Intra, R. Orecchia, G. Catalano, V. Galimberti, F. Nolé, G. Martinelli, A. Goldhirsch
Journal: Annals of Oncology (2002)
Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study
Authors: Emanuel Christ, Damian Wild, Susanne Ederer, Martin Béhé, Guillaume Nicolas, Martyn E Caplin, Michael Brändle, Thomas Clerici, Stefan Fischli, Christoph Stettler, Peter J Ell, Jochen Seufert, Beat Gloor, Aurel Perren, Jean Claude Reubi, Flavio Forrer
Journal: The Lancet Diabetes & Endocrinology (2013)

BackgroundSmall benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques.MethodsIn our prospective imaging study, we enrolled adults aged 25–81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of 111In-[Lys40(Ahx-DTPA-111In)NH2]-exendin-4 (111In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically.FindingsBetween Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent 111In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. 111In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62–94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by 111In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of 111In-DTPA-exendin-4 imaging alone. For 23 assessable patients, 111In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% [95% CI 74–100]) than did CT/MRI (47% [27–68]; p=0·011).Interpretation111In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI.FundingOncosuisse, the Swiss National Science Foundation, and UK Department of Health.
Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials
Authors: Michelle L O'Donoghue, Eugene Braunwald, Elliott M Antman, Sabina A Murphy, Eric R Bates, Yoseph Rozenman, Alan D Michelson, Raymond W Hautvast, Peter N Ver Lee, Sandra L Close, Lei Shen, Jessica L Mega, Marc S Sabatine, Stephen D Wiviott
Journal: The Lancet (2009)
Systemic chemotherapy and surgical cytoreduction for poorly differentiated and signet ring cell adenocarcinomas of the appendix
Authors: C.H. Lieu, L.A. Lambert, R.A. Wolff, C. Eng, N. Zhang, S. Wen, S. Rafeeq, M. Taggart, K. Fournier, R. Royal, P. Mansfield, M.J. Overman
Journal: Annals of Oncology (2011)
Targeting Notch to Target Cancer Stem Cells
Authors: Antonio Pannuti, Kimberly Foreman, Paola Rizzo, Clodia Osipo, Todd Golde, Barbara Osborne, Lucio Miele
Journal: Clinical Cancer Research (2010)

The cellular heterogeneity of neoplasms has been at the center of considerable interest since the "cancer stem cell hypothesis", originally formulated for hematologic malignancies, was extended to solid tumors. The origins of cancer "stem" cells (CSC) or tumor-initiating cells (TIC; henceforth referred to as CSCs) and the methods to identify them are hotly debated topics. Nevertheless, the existence of subpopulations of tumor cells with stem-like characteristics has significant therapeutic implications. The stem-like phenotype includes indefinite self-replication, pluripotency, and, importantly, resistance to chemotherapeutics. Thus, it is plausible that CSCs, regardless of their origin, may escape standard therapies and cause disease recurrences and/or metastasis after apparently complete remissions. Consequently, the idea of selectively targeting CSCs with novel therapeutics is gaining considerable interest. The Notch pathway is one of the most intensively studied putative therapeutic targets in CSC, and several investigational Notch inhibitors are being developed. However, successful targeting of Notch signaling in CSC will require a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to prove safe and effective. Additionally, to determine which patients are most likely to benefit from treatment with Notch-targeting therapeutics, reliable biomarkers to measure pathway activity in CSC from specific tumors will have to be identified and validated. This article summarizes the most recent developments in the field of Notch-targeted cancer therapeutics, with emphasis on CSC.
Faustian bargains for minorities within group-based hierarchies
Authors: C. David Navarrete, Melissa M. McDonald
Journal: Behavioral and Brain Sciences (2012)

Abstract A dual-audience signaling problem framework provides a deeper understanding of the perpetuation of group-based inequality. We describe a model of underachievement among minority youth that posits a necessary trade-off between academic success and peer social support that creates a dilemma not typically encountered by nonminorities. Preliminary evidence consistent with the approach is discussed. Such strategic agent perspectives complement the psychological approach put forth by Dixon et al., but with minimal ancillary assumptions.
Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6)
Authors: Christopher R Ingraham, Akira Kinoshita, Shinji Kondo, Baoli Yang, Samin Sajan, Kurt J Trout, Margaret I Malik, Martine Dunnwald, Stephen L Goudy, Michael Lovett, Jeffrey C Murray, Brian C Schutte
Journal: Nature Genetics (2006)
Spread of artemisinin-resistant Plasmodium falciparum in Myanmar: a cross-sectional survey of the K13 molecular marker
Authors: Kyaw M Tun, Mallika Imwong, Khin M Lwin, Aye A Win, Tin M Hlaing, Thaung Hlaing, Khin Lin, Myat P Kyaw, Katherine Plewes, M Abul Faiz, Mehul Dhorda, Phaik Yeong Cheah, Sasithon Pukrittayakamee, Elizabeth A Ashley, Tim J C Anderson, Shalini Nair, Marina McDew-White, Jennifer A Flegg, Eric P M Grist, Philippe Guerin, Richard J Maude, Frank Smithuis, Arjen M Dondorp, Nicholas P J Day, François Nosten, Nicholas J White, Charles J Woodrow
Journal: The Lancet Infectious Diseases (2015)

BackgroundEmergence of artemisinin resistance in southeast Asia poses a serious threat to the global control of Plasmodium falciparum malaria. Discovery of the K13 marker has transformed approaches to the monitoring of artemisinin resistance, allowing introduction of molecular surveillance in remote areas through analysis of DNA. We aimed to assess the spread of artemisinin-resistant P falciparum in Myanmar by determining the relative prevalence of P falciparum parasites carrying K13-propeller mutations.MethodsWe did this cross-sectional survey at malaria treatment centres at 55 sites in ten administrative regions in Myanmar, and in relevant border regions in Thailand and Bangladesh, between January, 2013, and September, 2014. K13 sequences from P falciparum infections were obtained mainly by passive case detection. We entered data into two geostatistical models to produce predictive maps of the estimated prevalence of mutations of the K13 propeller region across Myanmar.FindingsOverall, 371 (39%) of 940 samples carried a K13-propeller mutation. We recorded 26 different mutations, including nine mutations not described previously in southeast Asia. In seven (70%) of the ten administrative regions of Myanmar, the combined K13-mutation prevalence was more than 20%. Geospatial mapping showed that the overall prevalence of K13 mutations exceeded 10% in much of the east and north of the country. In Homalin, Sagaing Region, 25 km from the Indian border, 21 (47%) of 45 parasite samples carried K13-propeller mutations.InterpretationArtemisinin resistance extends across much of Myanmar. We recorded P falciparum parasites carrying K13-propeller mutations at high prevalence next to the northwestern border with India. Appropriate therapeutic regimens should be tested urgently and implemented comprehensively if spread of artemisinin resistance to other regions is to be avoided.FundingWellcome Trust–Mahidol University–Oxford Tropical Medicine Research Programme and the Bill & Melinda Gates Foundation.
Proton Pump Inhibitor and Histamine 2 Receptor Antagonist Use and Vitamin B<sub>12</sub>Deficiency
Authors: Jameson R. Lam, Jennifer L. Schneider, Wei Zhao, Douglas A. Corley
Journal: JAMA (2013)

Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B12. However, few data exist regarding the associations between long-term exposure to these medications and vitamin B12 deficiency in large population-based studies.To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States.We evaluated the association between vitamin B12 deficiency and prior use of acid-suppressing medication using a case-control study within the Kaiser Permanente Northern California population. We compared 25,956 patients having incident diagnoses of vitamin B12 deficiency between January 1997 and June 2011 with 184,199 patients without B12 deficiency. Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and diagnostic databases.Risk of vitamin B12 deficiency was estimated using odds ratios (ORs) from conditional logistic regression.Among patients with incident diagnoses of vitamin B12 deficiency, 3120 (12.0%) were dispensed a 2 or more years' supply of PPIs, 1087 (4.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 21,749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13,210 (7.2%) were dispensed a 2 or more years' supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 165,092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Both a 2 or more years' supply of PPIs (OR, 1.65 [95% CI, 1.58-1.73]) and a 2 or more years' supply of H2RAs (OR, 1.25 [95% CI, 1.17-1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95% CI, 1.48-1.78]; P = .007 for interaction).Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.
Thrombogenic Effect of High-Dose Aspirin in Rabbits
Authors: J. G. Kelton, J. Hirsh, C. J. Carter, M. R. Buchanan
Journal: Journal of Clinical Investigation (1978)

Aspirin is a promising antithrombogenic agent. It inhibits the generation of thromboxane A(2) by acetylating platelet cyclo-oxygenase. Aspirin also inhibits vessel wall production of PGI(2) which is an inhibitor of platelet aggregation, and therefore is potentially thrombotic. To investigate these two opposing effects we studied the effects of aspirin upon fibrin accretion onto experimentally induced venous thrombi in rabbits and on the PGI(2)-like activity of vessel wall using the thrombin-induced [(14)C]serotonin release assay. A 200-mg/kg dose of aspirin significantly augmented thrombus size when compared to (a) sodium salicylate administered in equal doses, (b) aspirin in a 10-mg/kg dose or (c) controls (P < 0.001). A 200-mg/kg dose of aspirin totally inhibited vessel wall PGI(2)-like activity whereas aspirin in a 10-mg/kg dose produced less inhibition, and 200 mg/kg sodium salicylate had no effect. Local instillation of tranylcypromine, an inhibitor of PGI(2) formation, also significantly augmented thrombus size compared to saline-treated controls and totally inhibited the production of PGI(2)-like activity. The thrombogenic effect of high dose aspirin was lost if an interval of 2.5 h or longer elapsed between vessel damage and drug administration, indicating that in contrast to the platelet, the effect of aspirin on vessel wall prostaglandin synthesis is relatively short-lived. It is concluded that aspirin, in doses higher than those used clinically, can augment experimental thrombosis, presumably by inhibiting the synthesis of vessel wall PGI(2).