tbuckley/cabot-search huggingface dataset:
The Complement Component 5 Gene and Age-Related Macular Degeneration
Authors: Dominique C. Baas, Lintje Ho, Sarah Ennis, Joanna E. Merriam, Michael W.T. Tanck, André G. Uitterlinden, Paulus T.V.M. de Jong, Angela J. Cree, Helen L. Griffiths, Fernando Rivadeneira, Albert Hofman, Cornelia van Duijn, R. Theodore Smith, Gaetano R. Barile, Theo G.M.F. Gorgels, Johannes R. Vingerling, Caroline C.W. Klaver, Andrew J. Lotery, Rando Allikmets, Arthur A.B. Bergen
Journal: Ophthalmology (2009)
Beyond the mirror neuron – the smoke neuron?
Authors: Derek Bickerton
Journal: Behavioral and Brain Sciences (2005)

Mirror neurons form a poor basis for Arbib's account of language evolution, failing to explain the creativity that must precede imitation, and requiring capacities (improbable in hominids) for categorizing situations and unambiguously miming them. They also commit Arbib to an implausible holophrastic protolanguage. His model is further vitiated by failure to address the origins of symbolization and the real nature of syntax.
Polymorphisms of <i>LIG4, BTBD2, HMGA2</i>, and <i>RTEL1</i> Genes Involved in the Double-Strand Break Repair Pathway Predict Glioblastoma Survival
Authors: Yanhong Liu, Sanjay Shete, Carol J. Etzel, Michael Scheurer, George Alexiou, Georgina Armstrong, Spyros Tsavachidis, Fu-Wen Liang, Mark Gilbert, Ken Aldape, Terri Armstrong, Richard Houlston, Fay Hosking, Lindsay Robertson, Yuanyuan Xiao, John Wiencke, Margaret Wrensch, Ulrika Andersson, Beatrice S. Melin, Melissa Bondy
Journal: Journal of Clinical Oncology (2010)

Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment.Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; <or= 12 months) and long-term survivors (LTS; >or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs.We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years).Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.
Lenalidomide in Nonmetastatic Biochemically Relapsed Prostate Cancer: Results of a Phase I/II Double-Blinded, Randomized Study
Authors: Daniel Keizman, Marianna Zahurak, Victoria Sinibaldi, Michael Carducci, Samuel Denmeade, Charles Drake, Roberto Pili, Emmanuel S. Antonarakis, Susan Hudock, Mario Eisenberger
Journal: Clinical Cancer Research (2010)

To evaluate the safety and activity of 6 months of treatment with lenalidomide at 5 or 25 mg/d in nonmetastatic biochemically relapsed prostate cancer.
Adherence to Antiretroviral Prophylaxis for HIV Prevention: A Substudy Cohort within a Clinical Trial of Serodiscordant Couples in East Africa
Authors: Jessica E. Haberer, Jared M. Baeten, James Campbell, Jonathan Wangisi, Elly Katabira, Allan Ronald, Elioda Tumwesigye, Christina Psaros, Steven A. Safren, Norma C. Ware, Katherine K. Thomas, Deborah Donnell, Meighan Krows, Lara Kidoguchi, Connie Celum, David R. Bangsberg
Journal: PLoS Medicine (2013)

Jessica Haberer and colleagues investigate the association between high adherence to antiretroviral pre-exposure prophylaxis and HIV transmission in a substudy of serodiscordant couples participating in a clinical trial. Please see later in the article for the Editors' Summary
Taxane-Mediated Antiangiogenesis <b> <i>in Vitro</i> </b>
Authors: Sylvia S. W. Ng, William D. Figg, Alex Sparreboom
Journal: Cancer Research (2004)

Abstract Paclitaxel (Taxol) and docetaxel (Taxotere) have been shown to inhibit angiogenesis at low concentrations that do not affect cancer cell proliferation. Here, we used rat aortic rings and human umbilical vein endothelial cells to evaluate the influence of their formulation vehicles Cremophor EL and polysorbate 80, as well as serum binding proteins on taxane-mediated antiangiogenesis. The data show that clinically relevant concentrations of the vehicles and binding proteins nullify the antiangiogenic activity of both taxanes. It is suggested that these agents may need to be used at much higher doses than anticipated for effective antiangiogenic chemotherapy.
Maternal Physical Activity and Insulin Action in Pregnancy and Their Relationships With Infant Body Composition
Authors: Jeremy Pomeroy, Frida Renström, Anna M. Gradmark, Ingrid Mogren, Margareta Persson, Les Bluck, Antony Wright, Steven E. Kahn, Magnus Domellöf, Paul W. Franks
Journal: Diabetes Care (2012)

We sought to assess the association between maternal gestational physical activity and insulin action and body composition in early infancy.At 28-32 weeks' gestation, pregnant women participating in an observational study in Sweden underwent assessments of height, weight, and body composition, an oral glucose tolerance test, and 10 days of objective physical activity assessment. Thirty mothers and infants returned at 11-19 weeks postpartum. Infants underwent assessments of weight, length, and body composition.Early insulin response was correlated with total physical activity (r = -0.47; P = 0.007). Early insulin response (r = -0.36; P = 0.045) and total physical activity (r = 0.52; P = 0.037) were also correlated with infant fat-free mass. No maternal variable was significantly correlated with infant adiposity.The relationships between maternal physical activity, insulin response, and infant fat-free mass suggest that physical activity during pregnancy may affect metabolic outcomes in the mother and her offspring.
Repurposing To Fight Cancer: The Metformin-Prostate Cancer Connection
Authors: A. Azvolinsky
Journal: JNCI Journal of the National Cancer Institute (2014)

Already recommended as a first-line therapy for diabetic men diagnosed with prostate cancer, metformin is one of the most widely prescribed drugs in the world. Diabetics use it every day to control blood sugar. Oncology may offer another use for the drug. Results from retrospective studies have been mixed depending on whether the study examined prevention or cancer outcomes. But on the basis of recent evidence, researchers suggest that it may be time to conduct prospective trials of metformin to test its effectiveness on prostate cancer progression. In one study, diabetic men with prostate cancer who took metformin were less likely to die from their cancer and lived statistically significantly longer irrespective of prostate cancer treatment received (J. Clin. Oncol. 2013;31:3069–75). The same analysis, by Neil Fleshner, M.D., of the Princess Margaret Hospital in Toronto, Canada, showed a 24% decrease in death from prostate cancer for each cumulative 6 months of treatment with metformin. The almost-3,900-patient retrospective study showed that this benefit was specific to metformin: Other diabetes drugs did not have the same effect. This is one of many retrospective studies linking metformin with prostate cancer, but not all are positive. Another population study, also by Fleshner, showed that diabetic men taking metformin did not have a lower incidence of prostate cancer (J. Natl. Cancer Inst. 2013;105:1123–31). The different origins of indolent and aggressive prostate cancer may account for the dissimilar results for incidence and disease progression. “The data suggest that metformin use may affect the aggressive type,” said David Margel, MD, PhD, of the University of Toronto, Canada, and first author of both described studies. Meir J. Stampfer, MD, an epidemiologist at the Harvard School of Public Health in Boston, agrees. “Studies attempting to identify risk factors for overall prostate cancer incidence often produce conflicting results as a consequence of that difference,” Stampfer wrote with coauthor Kathryn L. Penney, ScD, in an accompanying editorial (J. Clin. Oncol. 2013;31:3054–5). Stampfer supports a large, long-term randomized metformin trial in men with localized prostate cancer, regardless of whether they have diabetes. “There is a genuine question here that requires a randomized trial,” Stampfer said.
Low Serum Level of the Endogenous Secretory Receptor for Advanced Glycation End Products (esRAGE) Is a Risk Factor for Prevalent Vertebral Fractures Independent of Bone Mineral Density in Patients With Type 2 Diabetes
Authors: Sho-ichi Yamagishi
Journal: Diabetes Care (2010)

I have recently read an interesting article in Diabetes Care (1) that showed that the low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) was independently associated with the prevalence of vertebral fractures in patients with type 2 diabetes. I totally agreed with the authors' opinions that bone quality may be more important than bone density in defining the increased risk for fracture in type 2 diabetic patients and that the advanced glycation end product (AGE)–receptor for AGEs (RAGE) system could play a role in impaired bone quality in these patients. However, it seemed unlikely to me that an insufficient amount of esRAGE to counteract AGEs could intensify the binding of AGEs to …
PMO-043 Outcome of percutaneous endoscopic gastrostomy—how compliant we are with BSG guidelines?
Authors: I Ahmed, K Belfield, D Slim, R Patel, P Marden
Journal: Gut (2012)

<h3>Introduction</h3> Maintenance of enteral nutrition is considered to be beneficial for patients in whom the oral access has been lost. For long term tube feeding, PEG (percutaneous endoscopic gastrostomy) placement is of recognised advantage. A significant number of PEG tubes continue to be placed in patients for whom the benefits are questionable which account for significant procedure related morbidity and mortality. A better understanding of patient selection, designated multi-disciplinary framework and compliance with BSG guidelines are thought to improve outcome and minimise morbidity and mortality. <h3>Methods</h3> We evaluated our practice of PEG tube placement against BSG guidelines in terms of patient selection, assessment, outcome and complications. It was a retrospective study. Medical record of patients who had PEG tube placement between February 2010 and March 2011 were studied. PEG related information was collected from endoscopy database and hospital electronic resources. Data were collected regarding pre-procedure clinical assessment, blood investigations, MRSA status, family involvement in decision making, underlying co-morbidities, post PEG care, early and late complications and 30 days mortality. <h3>Results</h3> 52 patients aged 25–90 yrs (median age=78, F=28) were identified. 60% of the patients were assessed by a member of gastroenterology team prior to the procedure. Indications of PEG recorded were stroke (71%), pharyngeal cancer (10%), unsafe swallow (10%) and neurological condition (9%). Clotting was checked in 73% and MRSA status in 64% of cases. Family was involved in decision making in 73% of cases. 86% were reviewed by dietician pre or post procedure. 33% had early complications (within 1 week of the procedure, majority were pneumonia) while 12% had late complications (&gt;1 week after PEG). 30 days mortality was 33% and 4% died within 2 days of the procedure. Overall compliance with BSG guidelines was unsatisfactory. <h3>Conclusion</h3> PEG tube provides a durable access for enteral nutrition, whether or not it improves outcome, remains a matter of much debate. Guidelines have been developed by BSG to assist physicians in decision-making in order to minimise the morbidity and mortality associated with this procedure. A dedicated multi-disciplinary PEG team and better compliance with these guidelines would be an important strategy to improve outcome and minimise complications. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <i>BSG Guidelines For Percutaneously Placed Entral Tubes</i>. 2010. 2. <b>NCEPOD.</b><i>Scoping Our Practice</i>. <i>The 2004 Report Of The National Confidential Enquiry Into Patient Outcome And Death</i>. London: NCEPOD, 2004.
Risk Factors for Depression Among Elderly Community Subjects: A Systematic Review and Meta-Analysis
Authors: Martin G Cole, Nandini Dendukuri
Journal: American Journal of Psychiatry (2003)

The goal of this study was to determine risk factors for depression among elderly community subjects.MEDLINE and PsycINFO were searched for potentially relevant articles published from January 1966 to June 2001 and from January 1967 to June 2001, respectively. The bibliographies of relevant articles were searched for additional references. Twenty studies met the following six inclusion criteria: original research reported in an English or French publication, study group of community residents, age of subjects 50 years or more, prospective study design, examination of at least one risk factor, and use of an acceptable definition of depression. The validity of studies was assessed according to the four primary criteria for risk factor studies described by the Evidence-Based Medicine Working Group. Information about group size at baseline and follow-up, age, proportion of men, depression criteria, exclusion criteria at baseline, length of follow-up, number of incident cases of depression, and risk factors was abstracted from each report.Follow-up of the inception cohort was incomplete in most studies. In the qualitative meta-analysis, risk factors identified by both univariate and multivariate techniques in at least two studies each were disability, new medical illness, poor health status, prior depression, poor self-perceived health, and bereavement. In the quantitative meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender were significant risk factors.Despite the methodologic limitations of the studies and this meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender appear to be important risk factors for depression among elderly community subjects.
Increased Central Venous Pressure Is Associated With Impaired Renal Function and Mortality in a Broad Spectrum of Patients With Cardiovascular Disease
Authors: Kevin Damman, Vincent M. van Deursen, Gerjan Navis, Adriaan A. Voors, Dirk J. van Veldhuisen, Hans L. Hillege
Journal: Journal of the American College of Cardiology (2009)
The APOB R3500Q Polymorphism Is Common In The Old Order Amish And Is Associated With Low Density Lipoprotein Cholesterol Concentrations And Coronary Artery Calcification
Authors: Haiqing Shen
Journal: Circulation (2007)

Low density lipoprotein cholesterol (LDL-C) is a major cardiovascular disease (CVD) risk factor. Reduction in LDL-C levels reduces the incidence of CVD. To identify the genetic determinants of this trait, we carried out a whole genome association (WGA) scan in 861 relatively healthy Amish subjects aged 20 – 80 yrs from Lancaster County, PA, recruited for a study of cardiovascular health. Fewer than 2% of subjects reported a prior history of a cardiovascular event. The WGA scan, carried out using the Affymetrix 500K platform, revealed a cluster of single nucleotide polymorphisms (SNPs) in the region of the  APOB  gene on chromosome 2p24.1 to be strongly associated with both LDL-C levels (p  −60 ) and coronary artery calcification (CAC) score (p  −9 ), as measured by EBCT scan. Following sequencing of  APOB  exons revealed the presence of a mutation in exon 26 ( R3500Q ), whose allele frequency in European Caucasians was reported to be 0.04% to 0.2%. Subsequent genotyping of this mutation in more Amish individuals (n = 1,533) revealed an allele frequency of 6.1% and a carrier frequency of 12%. The mutation was strongly associated in additive fashion with levels of both LDL-C (P  −93 ) and CAC (P  −15 ) and accounted for 45% of the variation in LDL-C levels and 6% of the variation in CAC score. Carriers of the  R3500Q  mutation had approximately 60 mg per deciliter higher LDL-C levels and had a 4.33-fold higher odds (95% C.I.: 2.46 –7.62) of having any CAC compared to noncarriers. This allele accounted for 10% of severe CAC in the population.  Conclusion: The high frequency of the  APOB R3500Q  variant in the Amish population likely represents a founder effect. It is present in 1 of 8 –9 individuals in this population, causing hypercholesterolemia and increasing the risk of subclinical CVD.
Fluorescent light activates the immunomodulator cis-urocanic acid in vitro: implications for patients with systemic lupus erythematosus.
Authors: H McGrath, J.M. Bell, J.W. Haycock
Journal: Annals of the Rheumatic Diseases (1994)

Erythemagenic (295-305 nm) ultraviolet-B (UVB) radiation is toxic to patients with systemic lupus erythematosus (SLE). Cool white fluorescent lamp emissions produce a similar toxicity even though the UVB radiation emitted is primarily at the relatively non-erythemagenic wavelength of 313 nm. The purpose of this study was to determine if fluorescent light, presumably acting predominantly along the 313 nm wavelength, exhibits photochemical activity sufficient to account for toxicity. The photochemical activity of fluorescent light was assessed by testing its capacity to activate urocanic acid, a plentiful and potent epidermal immunological mediator normally activated by polychromatic UVB radiation but activated maximally at 313 nm. Irradiation-induced isomerisation of trans-urocanic to cis-urocanic acid was quantitated by UV spectroscopy after separation of the isomers by high performance liquid chromatography. Fluorescent light irradiation of solutions containing the photoreceptor trans-urocanic acid produced a cumulative conversion of trans-to-cis-urocanic acid. This photochemical activity was compared with that of erythemagenic sunlamps, high in polychromatic UVB emissions. When normalised for UVB irradiance, the accumulation of cis-urocanic acid produced by both light sources was essentially equivalent. Conventional acrylic diffusers that absorb UVB emissions eliminated the fluorescent light-induced reaction. The results indicate that radiation from fluorescent lamps possesses substantial photoimmunological capability, sufficient to activate a potent, potentially dangerous, disease-modifying, immunomodulatory pathway and that poorly erythemagenic, primarily monochromatic UVB photons are responsible.
Mithramycin Represses Basal and Cigarette Smoke–Induced Expression of<i>ABCG2</i>and Inhibits Stem Cell Signaling in Lung and Esophageal Cancer Cells
Authors: Mary Zhang, Aarti Mathur, Yuwei Zhang, Sichuan Xi, Scott Atay, Julie A. Hong, Nicole Datrice, Trevor Upham, Clinton D. Kemp, R. Taylor Ripley, Gordon Wiegand, Itzak Avital, Patricia Fetsch, Haresh Mani, Daniel Zlott, Robert Robey, Susan E. Bates, Xinmin Li, Mahadev Rao, David S. Schrump
Journal: Cancer Research (2012)

Abstract Cigarette smoking at diagnosis or during therapy correlates with poor outcome in patients with lung and esophageal cancers, yet the underlying mechanisms remain unknown. In this study, we observed that exposure of esophageal cancer cells to cigarette smoke condensate (CSC) led to upregulation of the xenobiotic pump ABCG2, which is expressed in cancer stem cells and confers treatment resistance in lung and esophageal carcinomas. Furthermore, CSC increased the side population of lung cancer cells containing cancer stem cells. Upregulation of ABCG2 coincided with increased occupancy of aryl hydrocarbon receptor, Sp1, and Nrf2 within the ABCG2 promoter, and deletion of xenobiotic response elements and/or Sp1 sites markedly attenuated ABCG2 induction. Under conditions potentially achievable in clinical settings, mithramycin diminished basal as well as CSC-mediated increases in AhR, Sp1, and Nrf2 levels within the ABCG2 promoter, markedly downregulated ABCG2, and inhibited proliferation and tumorigenicity of lung and esophageal cancer cells. Microarray analyses revealed that mithramycin targeted multiple stem cell–related pathways in vitro and in vivo. Collectively, our findings provide a potential mechanistic link between smoking status and outcome of patients with lung and esophageal cancers, and support clinical use of mithramycin for repressing ABCG2 and inhibiting stem cell signaling in thoracic malignancies. Cancer Res; 72(16); 4178–92. ©2012 AACR.
680 HCV NS3/4A INTERFERES WITH INTRAHEPATIC IMMUNITY AND TNFA-INDUCED LIVER DAMAGE BY MODULATING CCL17 AND CXCL9 SECRETION IN VIVO
Authors: E.D. Brenndörfer, L. Frelin, J. Söderholm, J.G. Bode, M. Sällberg
Journal: Journal of Hepatology (2010)
Full genome re-sequencing reveals a novel circadian clock mutation in Arabidopsis
Authors: Kevin Ashelford, Maria E Eriksson, Christopher M Allen, Rosalinda D'Amore, Mikael Johansson, Peter Gould, Suzanne Kay, Andrew J Millar, Neil Hall, Anthony Hall
Journal: Genome biology (2011)

Map based cloning in Arabidopsis thaliana can be a difficult and time-consuming process, specifically if the phenotype is subtle and scoring labour intensive. Here, we have re-sequenced the 120-Mb genome of a novel Arabidopsis clock mutant early bird (ebi-1) in Wassilewskija (Ws-2). We demonstrate the utility of sequencing a backcrossed line in limiting the number of SNPs considered. We identify a SNP in the gene AtNFXL-2 as the likely cause of the ebi-1 phenotype.
Deubiquitylation Regulates Activation and Proteolytic Cleavage of ENaC
Authors: Dorothe[Combining Acute Accent]e Ruffieux-Daidie[Combining Acute Accent], Olivier Poirot, Sheerazed Boulkroun, Franc[COMBINING CEDILLA]ois Verrey, Stephan Kellenberger, Olivier Staub
Journal: Journal of the American Society of Nephrology (2008)

Of 47 consecutive infants with extrahepatic biliary atresia, effective bile drainage with the return of the serum bilirubin concentration to normal, was achieved in 17 (38%). Direct bile duct-to-bowl anastomosis, attempted in 15 infants, produced bile drainage in only those 4 (9%) in whom bile could be seen within the bile duct remnants at laparotomy. 13 (45%) of 29 infants subjected to portoenterostomy (direct liver-to-bowel anastomosis) had satisfactory prolonged bile drainage with normal serum bilirubin values. Although a correct preoperative diagnosis was made in each case, in 3 (6%) the 72-hour faecal rose bengal 131I excretion was greater than 10% of the injected dose, and in 5 (11%) the hepatic histology did not indicate bile duct obstruction, showing that both investigations are necessary for preoperative diagnosis. Preoperative clinical, laboratory, and hepatic histological features in the 16 jaundice-free survivors showed no significant difference when compared with the 31 infants in whom surgery was successful. Cholangitis occurred in only 7 (43%) of 16 infants with satisfactory bile drainage and was easily controlled with antibiotic treatment. No cutaneous enterostomies were performed. In most survivors liver function tests remain abnormal, but the patients are symptom-free. While it is too early to predict a long-term prognosis for these children, our eldest survivors are healthy and show normal development.
816-3 Interaction of age and gender on risk stratification of diabetic patients with rest/stress ECG-gated Tc-99m sestamibi SPECT imaging
Authors: Sachin M Navare, Safi U Ahmed, Gavin L Noble, Alan W Ahlberg, Deborah M Katten, Giselle Cyr, Leslee J Shaw, William E Boden, Gary V Heller
Journal: Journal of the American College of Cardiology (2004)