tbuckley/cabot-search huggingface dataset:
Processing Speed, Attention, and Working Memory After Treatment for Medulloblastoma: An International, Prospective, and Longitudinal Study
Authors: Shawna L. Palmer, Carol Armstrong, Arzu Onar-Thomas, Shengjie Wu, Dana Wallace, Melanie J. Bonner, Jane Schreiber, Michelle Swain, Lynn Chapieski, Donald Mabbott, Sarah Knight, Robyn Boyle, Amar Gajjar
Journal: Journal of Clinical Oncology (2013)

The current study prospectively examined processing speed (PS), broad attention (BA), and working memory (WM) ability of patients diagnosed with medulloblastoma over a 5-year period.The study included 126 patients, ages 3 to 21 years at diagnosis, enrolled onto a collaborative protocol for medulloblastoma. Patients were treated with postsurgical risk-adapted craniospinal irradiation (n = 36 high risk [HR]; n = 90 average risk) followed by four cycles of high-dose chemotherapy with stem-cell support. Patients completed 509 neuropsychological evaluations using the Woodcock-Johnson Tests of Cognitive Abilities Third Edition (median of three observations per patient).Linear mixed effects models revealed that younger age at diagnosis, HR classification, and higher baseline scores were significantly associated with poorer outcomes in PS. Patients treated as HR and those with higher baseline scores are estimated to have less favorable outcomes in WM and BA over time. Parent education and marital status were significantly associated with BA and WM baseline scores but not change over time.Of the three key domains, PS was estimated to have the lowest scores at 5 years after diagnosis. Identifying cognitive domains most vulnerable to decline should guide researchers who are aiming to develop efficacious cognitive intervention and rehabilitation programs, thereby improving the quality of survivorship for the pediatric medulloblastoma population.
On the Proliferation of Bioethics Sub-Disciplines: Do We Really Need “Genethics” and “Neuroethics”?
Authors: Benjamin S. Wilfond, Vardit Ravitsky
Journal: The American Journal of Bioethics (2005)

Click to increase image sizeClick to decrease image size Acknowledgments The opinions expressed in this article are those of the authors and do not reflect the opinions or policies of the National Human Genome Research Institute, the National Institutes of Health, or the Department of Health and Human Services.
Upper and lower airway microbiology in cystic fibrosis
Authors: T Daniels
Journal: Thorax (2010)

with regard to disclosure of serious or risks which was tailored in the majority if the patient underwent transbronchial biopsy (figure 1).Particular risks were represented in terms of an exact percentage in 15 and in 6 by means of words (eg, occasional, common).Fifteen respondents tailored their consent in the presence of significant co-morbidity.Risk of death was communicated always by 3 respondents, often by 1, sometimes by 15 and never by 14.The current British Thoracic Society guidance on consent for bronchoscopy from 2001 2 reflected the legal and ethical standard at that time where doctors were "entitled to withhold information" if it was thought to be detrimental to patient health and were under "no duty .to point out remote risks".The ethicolegal landscape has been changed dramatically by rulings such as Chester v Afshar, 3 and this is reflected in the recent General Medical Council publication on consent 4 which states that a doctor "must tell patients if an investigation or treatment might result in a serious adverse outcome, even if the likelihood is very small".We feel that all patients with capacity undergoing bronchoscopy should be offered detailed risk disclosure with documentation of the decision in those patients wishing to "opt out", and that this risk information should become standardised and individually tailored where possible.
A New Design and Application of Bioelastomers for Better Control of Intraocular Pressure in a Glaucoma Drainage Device
Authors: Quang Minh Luong, Lei Shang, Marcus Ang, Jen Fong Kong, Yan Peng, Tina T. Wong, Subbu S. Venkatraman
Journal: Advanced Healthcare Materials (2013)

Glaucoma drainage device (GDD) implantation is an effective method of lowering the intraocular pressure (IOP). Commonly used GDDs can be classified into nonvalved and valved. Although a stable IOP is critical, currently available devices often cause extreme IOP fluctuations: nonvalved GDDs suffer from a risk of hypotony (IOP<5 mmHg), whereas valved GDDs have a higher risk ocular hypertensive (IOP>22 mmHg). It is hypothesized that a GDD with a valve designed to open around the time of onset of the hypertensive phase, would minimize IOP fluctuation. Accordingly, a valve fabricated from a biodegradable polymer poly(L-lactide-co-ϵ-caprolactone) (PLC 70/30) is evaluated in vitro and in vivo. The pressure response is compared with its non-degradable counterpart in in vitro studies of IOP. It is also established that in vitro, the biodegradability of the valve is programmed to occur over 12 weeks. In vivo, a steady and low IOP is achieved with the biodegradable valve and the hypertensive phase is significantly attenuated compared with the commercial device. Fibrotic encapsulation of the device is also minimized with the biodegradable valve in vivo.
Normalizing Metabolism in Diabetic Pregnancy: Is It Time to Target Lipids?
Authors: Helen L. Barrett, Marloes Dekker Nitert, H. David McIntyre, Leonie K. Callaway
Journal: Diabetes Care (2014)

Outcomes in pregnancies complicated by preexisting diabetes (type 1 and type 2) and gestational diabetes mellitus have improved, but there is still excess morbidity compared with normal pregnancy. Management strategies appropriately focus on maternal glycemia, which demonstrably improves pregnancy outcomes for mother and infant. However, we may be reaching the boundaries of obtainable glycemic control for many women. It has been acknowledged that maternal lipids are important in pregnancies complicated by diabetes. Elevated maternal lipids are associated with preeclampsia, preterm delivery, and large-for-gestational-age infants. Despite this understanding, assessment of management strategies targeting maternal lipids has been neglected to date. Consideration needs to be given to whether normalizing maternal lipids would further improve pregnancy outcomes. This review examines the dyslipidemia associated with pregnancy complicated by diabetes, reviews possible therapies, and considers whether it is time to start actively managing this aspect of maternal metabolism.
Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metabolomics (SIRM)
Authors: Teresa WM Fan, Andrew N Lane, Richard M Higashi, Mohamed A Farag, Hong Gao, Michael Bousamra, Donald M Miller
Journal: Molecular Cancer (2009)

Metabolic perturbations arising from malignant transformation have not been systematically characterized in human lung cancers in situ. Stable isotope resolved metabolomic analysis (SIRM) enables functional analysis of gene dysregulations in lung cancer. To this purpose, metabolic changes were investigated by infusing uniformly labeled 13C-glucose into human lung cancer patients, followed by resection and processing of paired non-cancerous lung and non small cell carcinoma tissues. NMR and GC-MS were used for 13C-isotopomer-based metabolomic analysis of the extracts of tissues and blood plasma. Many primary metabolites were consistently found at higher levels in lung cancer tissues than their surrounding non-cancerous tissues. 13C-enrichment in lactate, Ala, succinate, Glu, Asp, and citrate was also higher in the tumors, suggesting more active glycolysis and Krebs cycle in the tumor tissues. Particularly notable were the enhanced production of the Asp isotopomer with three 13C-labeled carbons and the buildup of 13C-2,3-Glu isotopomer in lung tumor tissues. This is consistent with the transformations of glucose into Asp or Glu via glycolysis, anaplerotic pyruvate carboxylation (PC), and the Krebs cycle. PC activation in tumor tissues was also shown by an increased level of pyruvate carboxylase mRNA and protein. PC activation – revealed here for the first time in human subjects – may be important for replenishing the Krebs cycle intermediates which can be diverted to lipid, protein, and nucleic acid biosynthesis to fulfill the high anabolic demands for growth in lung tumor tissues. We hypothesize that this is an important event in non-small cell lung cancer and possibly in other tumor development.
Microarray-based characterisation of a Panton–Valentine leukocidin-positive community-acquired strain of methicillin-resistant Staphylococcus aureus
Authors: S. Monecke, P. Slickers, H. Hotzel, G. Richter-Huhn, M. Pohle, S. Weber, W. Witte, R. Ehricht
Journal: Clinical Microbiology and Infection (2006)
Conventional testing methods produce submaximal values of maximum oxygen consumption
Authors: Fernando G Beltrami, Christian Froyd, Alexis R Mauger, Alan J Metcalfe, Frank Marino, Timothy D Noakes
Journal: British Journal of Sports Medicine (2011)

Background This study used a novel protocol to test the hypothesis that a plateau in oxygen consumption (VO 2max ) during incremental exercise testing to exhaustion represents the maximal capacity of the cardiovascular system to transport oxygen. Methods Twenty-six subjects were randomly divided into two groups matched by their initial VO 2max . On separate days, the reverse group performed (i) an incremental uphill running test on a treadmill (INC 1 ) plus verification test (VER) at a constant workload 1 km h −1 higher than the last completed stage in INC 1 ; (ii) a decremental test (DEC) in which speed started as same as the VER but was reduced progressively and (iii) a final incremental test (INC F ). The control group performed only INC on the same days that the reverse group was tested. Results VO 2max remained within 0.6 ml kg −1 min −1 across the three trials for the control group (p=0.93) but was 4.4% higher during DEC compared with INC 1 (63.9±3.8 vs 61.2±4.8 ml kg −1 min −1 , respectively, p=0.004) in the reverse group, even though speed at VO 2max was lower (14.3±1.1 vs 16.2±0.7 km h −1 for DEC and INC 1 , respectively, p=0.0001). VO 2max remained significantly higher during INC F (63.6±3.68 ml kg −1 min −1 , p=0.01), despite an unchanged exercise time between INC 1 and INC F . Conclusion These findings go against the concept that a plateau in oxygen consumption measured during the classically described INC and VER represents a systemic limitation to oxygen use. The reasons for a higher VO 2 during INC F following the DEC test are unclear.
Abstract 862: Purified recombinant Maspin is processed through the endosomal pathway in breast cancer cells.
Authors: Thomas M. Bodenstine, Richard E. B. Seftor, Elisabeth A. Seftor, Zhila Khalkhali-Ellis, Nicole A. Samii, J. Cesar Monarrez, Philip A. Pemberton, Mary J. C. Hendrix
Journal: Cancer Research (2013)

Abstract Maspin (Mammary Serine Protease Inhibitor), a gene involved in mammary gland development and morphogenesis, has been shown to act as a tumor suppressor in multiple cancers by inhibiting the aggressive cancer cell phenotype. Recombinant Maspin (rMas) added to cell culture media is internalized by cancer cells and capable of recapitulating many of the effects of endogenously re-expressed Maspin in Maspin-null cancer cells, including the inhibition of cell invasion, migration and induction of angiogenesis. Importantly, these effects are mediated by purified rMas without the need for post-translational modifications prior to application, increasing the future therapeutic potential for utilizing rMas as an adjuvant therapy. However, the therapeutic use of rMas is limited by its rapid clearance from cancer cells, and many of the molecular mechanisms regarding rMas internalization and processing remain to be determined. Building on preliminary data, we hypothesized that rMas is processed by the endosomal pathway. We demonstrate localization of rMas in Rab9 late-endosomes and Lamp-1 positive lysosomes following treatment of 10 μg/ml rMas in BT549, Hs578T and MDA-MB-231 human breast cancer cell lines. rMas internalization was reduced when incubated at 4oC, and increased at temperatures of 20oC and 37oC, with the highest rates of internalization at 37oC, indicative of endocytosis. Furthermore, depletion of K+ decreased rMas internalization in Hs578T and MDA-MB-231, suggestive of clarthrin-mediated endocytosis. Our data show that rMas is capable of acting at the membrane to mediate effects on invasion and migration, but may not be functional once internalized due to rapid degradation by the lysosome. Interestingly, this may provide a plausible explanation for previously reported data in which rMas was not able to reproduce the effects of endogenous Maspin re-expression on cancer cell apoptosis sensitivity, which require cytosolic and mitochondrial mechanisms. Our data provide evidence that strategies which induce endosomal escape of rMas will intensify its anti-tumor effects on cancer cells, and further enhance its potential therapeutic applications. Citation Format: Thomas M. Bodenstine, Richard E. B. Seftor, Elisabeth A. Seftor, Zhila Khalkhali-Ellis, Nicole A. Samii, J. Cesar Monarrez, Philip A. Pemberton, Mary J. C. Hendrix. Purified recombinant Maspin is processed through the endosomal pathway in breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 862. doi:10.1158/1538-7445.AM2013-862
Environmental organochlorines and semen quality: results of a pilot study.
Authors: Russ Hauser, Larisa Altshul, Zuying Chen, Louise Ryan, James Overstreet, Isaac Schiff, David C Christiani
Journal: Environmental Health Perspectives (2002)

There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress.
Advanced epithelial ovarian cancer: 1993 consensus statements
Authors: D.G. Allen, J. Baak, D. Belpomme, J.S. Berek, K. Bertelsen, W.W. ten Bokkel Huinink, M.E.L. van der Burg, A.H. Calvert, P.F. Conte, J. Dauplat, E.A. Eisenhauer, G. Favalli, N.F. Hacker, T.C. Hamilton, H.H. Hansen, M. Hansen, H.C. van Houwelingen, S.B. Kaye, L. Levin, B. Lund, J.P. Neijt, R .F. Ozols, M.J. Piccart, G.J.S. Rustin, C. Sessa, W.P. Soutter, J.T. Thigpen, C. Tropé, J.B. Vermorken, E.G.E. de Vries
Journal: Annals of Oncology (1993)
First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway
Authors: Margit Hagel, Chandra Miduturu, Michael Sheets, Nooreen Rubin, Weifan Weng, Nicolas Stransky, Neil Bifulco, Joseph L. Kim, Brian Hodous, Natasja Brooijmans, Adam Shutes, Christopher Winter, Christoph Lengauer, Nancy E. Kohl, Timothy Guzi
Journal: Cancer Discovery (2015)

Aberrant signaling through the fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR 4) signaling complex has been shown to cause hepatocellular carcinoma (HCC) in mice and has been implicated to play a similar role in humans. We have developed BLU9931, a potent and irreversible small-molecule inhibitor of FGFR4, as a targeted therapy to treat patients with HCC whose tumors have an activated FGFR4 signaling pathway. BLU9931 is exquisitely selective for FGFR4 versus other FGFR family members and all other kinases. BLU9931 shows remarkable antitumor activity in mice bearing an HCC tumor xenograft that overexpresses FGF19 due to amplification as well as a liver tumor xenograft that overexpresses FGF19 mRNA but lacks FGF19 amplification. Approximately one third of patients with HCC whose tumors express FGF19 together with FGFR4 and its coreceptor klotho β (KLB) could potentially respond to treatment with an FGFR4 inhibitor. These findings are the first demonstration of a therapeutic strategy that targets a subset of patients with HCC.This article documents the discovery of BLU9931, a novel irreversible kinase inhibitor that specifically targets FGFR4 while sparing all other FGFR paralogs and demonstrates exquisite kinome selectivity. BLU9931 is efficacious in tumors with an intact FGFR4 signaling pathway that includes FGF19, FGFR4, and KLB. BLU9931 is the first FGFR4-selective molecule for the treatment of patients with HCC with aberrant FGFR4 signaling.
Detection of Methylated Apoptosis-Associated Genes in Urine Sediments of Bladder Cancer Patients
Authors: Martin G. Friedrich, Daniel J. Weisenberger, Jonathan C. Cheng, Shahin Chandrasoma, Kimberly D. Siegmund, Mark L. Gonzalgo, Marieta I. Toma, Hartwig Huland, Christine Yoo, Yvonne C. Tsai, Peter W. Nichols, Bernard H. Bochner, Peter A. Jones, Gangning Liang
Journal: Clinical Cancer Research (2004)

There is increasing evidence for a fundamental role for epigenetic silencing of apoptotic pathways in cancer. Changes in DNA methylation can be detected with a high degree of sensitivity, so we used the MethyLight assay to determine how methylation patterns of apoptosis-associated genes change during bladder carcinogenesis and whether DNA methylation could be detected in urine sediments.We analyzed the methylation status of the 5' regions of 12 apoptosis-associated genes (ARF, FADD, TNFRSF21, BAX, LITAF, DAPK, TMS-1, BCL2, RASSF1A, TERT, TNFRSF25, and EDNRB) in 18 bladder cancer cell lines, 127 bladder cancer samples, and 37 samples of adjacent normal bladder mucosa using the quantitative MethyLight assay. We also analyzed the methylation status in urine sediments of 20 cancer-free volunteers and 37 bladder cancer patients.The 5' regions of DAPK, BCL2, TERT, RASSFIA, and TNFRSF25 showed significant increases in methylation levels when compared with nonmalignant adjacent tissue (P < or = 0.01). Methylation levels of BCL2 were significantly associated with tumor staging and grading (P < or = 0.01), whereas methylation levels of RASSF1A and ARF were only associated with tumor stage (P < or = 0.04), and TERT methylation and EDNRB methylation were predictors of tumor grade (P < or = 0.02). To investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status of the markers in urine samples of patients with bladder cancer. Methylation of DAPK, BCL2, and TERT in urine sediment DNA from bladder cancer patients was detected in the majority of samples (78%), whereas they were unmethylated in the urine sediment DNA from age-matched cancer-free individuals.Our results indicate that methylation of the 5' region of apoptosis-associated genes is a common finding in patients with bladder carcinoma. The ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancers. Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues.
Effect of Moderate Alcohol Consumption on Adiponectin, Tumor Necrosis Factor-α, and Insulin Sensitivity
Authors: Aafje Sierksma, Hamina Patel, Noriyuki Ouchi, Shinji Kihara, Tohru Funahashi, Robert J. Heine, Diederick E. Grobbee, Cornelis Kluft, Henk F.J. Hendriks
Journal: Diabetes Care (2004)

Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin, an adipocyte-derived plasma protein, has been found to be negatively associated with adiposity and positively associated with insulin sensitivity. Moderate alcohol consumption may increase adiponectin, which in turn causes a decrease of tumor necrosis factor (TNF)-alpha. A decreased TNF-alpha level may consequently increase insulin sensitivity.To test this hypothesis, we performed a randomized crossover partially diet-controlled study. A total of 23 healthy middle-aged male subjects consumed daily four glasses of whisky (40 g ethanol) or tap water with dinner during two successive periods of 17 days.Moderate alcohol consumption increased plasma adiponectin level (11%; P = 0.0002) but did not affect plasma TNF-alpha level. An increase in insulin sensitivity index was observed in an insulin-resistant subgroup (21%; P = 0.11), which positively correlated with the relative alcohol-induced increase in plasma adiponectin level (r = 0.73, P = 0.02).The experimental results are in agreement with observational data. Moderate alcohol consumption improved insulin sensitivity in relatively insulin-resistant middle-aged men, an effect that may be mediated through alcohol-induced increases in adiponectin.
THE STERILIZATION OF BACTERIOLOGICAL MEDIA AND OTHER FLUIDS WITH ETHYLENE OXIDE
Authors: Armine T. Wilson, Pauline Bruno
Journal: The Journal of Experimental Medicine (1950)

Ethylene oxide is an effective sterilizing agent for bacteriological broths, milk, and serum. A short time after it has exerted its sterilizing effect, the treated fluids again become capable of supporting bacterial growth. Ethylene oxide has been shown to destroy a number of aerobic Gram-positive and Gram-negative organisms, aerobic and anaerobic spore-forming bacilli, fungi, and vaccinia virus. No organisms have been encountered which withstand its action. The quantity of ethylene oxide necessary for sterilization depends to some degree on the character of the medium sterilized. None of the materials tested required more than 1 volume per cent of liquid ethylene oxide. Ethylene oxide is highly reactive chemically, and its reactions with many of the components of complex biological fluids cannot be fully anticipated. Regardless of the chemical changes produced, ethylene oxide did not permanently alter the essential qualities of the growth factors in broth and milk which are required by fastidious organisms such as group A streptococci and others. However, its effect on the biological activity of any particular organic compound should be assayed before it can be assumed not to have a deleterious effect. The sterilization of media by ethylene oxide is accompanied by a rise in pH. Fluids which have a relatively high initial pH may require adjustment with sterile acid to return them to the optimal pH for bacterial growth. A mixture of ethylene oxide and broth was toxic to mice for 6 hours after admixture. Toxicity disappeared on incubating the mixture longer, and no residual toxicity could be demonstrated after 6 hours, even on repeated intraperitoneal inoculations. As a means of sterilizing bacteriological media and other biological fluids, ethylene oxide deserves consideration when heat and filtration cannot be used.