tbuckley/cabot-search huggingface dataset:
Sport/performance psychology services to youth elite athletes: challenges and lessons learnt
Authors: Sanjana Kiran
Journal: British Journal of Sports Medicine (2010)

The age of an elite athlete is getting younger by the day. For some sports such as gymnastics, getting into an elite level at a very early age has always been emphasised. Today, many other sports seem to endorse this concept as well. Singapore hosted two significant inaugural youth sports events at an elite level, Asian Youth Games 2009 (AYG 2009) and Youth Olympic Games 2010 (YOG2010). Around 7000 international elite athletes participated in these two events. The challenges and lessons learnt in providing performance psychology services to elite youth athletes of Singapore representing AYG 2009 and YOG 2010 will be discussed.
Different effects of the Cdx1 and Cdx2 homeobox genes in a murine model of intestinal inflammation
Authors: A Calon, I Gross, B Lhermitte, E Martin, F Beck, B Duclos, M Kedinger, I Duluc, C Domon-Dell, J-N Freund
Journal: Gut (2007)

<h3>Aims:</h3> The CDX1 and CDX2 homeoproteins are intestine-specific transcription factors regulating homeostasis. We investigated their relevance in experimentally-induced intestinal inflammation. <h3>Methods:</h3> The response to intestinal inflammation induced by dextran sodium sulfate (DSS) was compared in wild type, Cdx1<sup>-/-</sup> and Cdx2<sup>+/−</sup> mice. Intestinal permeability was determined in wild type and Cdx2<sup>+/−</sup> mice. Protein-protein interactions were investigated by co-immunoprecipitation and GST-pulldown, and their functional consequences were assessed using Luciferase reporter systems. <h3>Results:</h3> Heterozygous Cdx2<sup>+/−</sup> mice, but not Cdx1<sup>-/-</sup> mice, were hypersensitive to DSS-induced acute inflammation as all these mice showed blood in the stools at day 1 of DSS treatment. Hypersensitivity was associated to a 50% higher intestinal permeability. In Cdx2<sup>+/-</sup> mice, the colonic epithelium was repaired during the week after the end of DSS treatment, whereas two weeks were required for wild type animals. Subsequently, no colonic tumour was observed in Cdx2<sup>+/−</sup> mice subjected to 5 repeated cycles of DSS, in contrast to the 2.7 tumours found per wild type mouse. Based on the fact that Smad3<sup>+/−</sup> mice, like Cdx2<sup>+/−</sup> mice, better repair the damaged intestinal epithelium, we found that the CDX2 protein interacts with SMAD3, independently of SMAD4, resulting in a 5-fold stimulation of SMAD3 transcriptional activity. CDX1 also interacted with SMAD3 but it inhibited by 10-fold the SMAD3/SMAD4-dependent transcription. <h3>Conclusion:</h3> The <i>Cdx1</i> and <i>Cdx2</i> homeobox genes have distinct effects on the outcome of a pro-inflammatory challenge. This is mirrored by different functional interactions of the CDX1 and CDX2 proteins with SMAD3, a major element of the TGFβ signalling pathway.
RAE-1 ligands for the NKG2D receptor are regulated by E2F transcription factors, which control cell cycle entry
Authors: Heiyoun Jung, Benjamin Hsiung, Kathleen Pestal, Emily Procyk, David H. Raulet
Journal: The Journal of Experimental Medicine (2012)

The NKG2D stimulatory receptor expressed by natural killer cells and T cell subsets recognizes cell surface ligands that are induced on transformed and infected cells and facilitate immune rejection of tumor cells. We demonstrate that expression of retinoic acid early inducible gene 1 (RAE-1) family NKG2D ligands in cancer cell lines and proliferating normal cells is coupled directly to cell cycle regulation. Raet1 genes are directly transcriptionally activated by E2F family transcription factors, which play a central role in regulating cell cycle entry. Induction of RAE-1 occurred in primary cell cultures, embryonic brain cells in vivo, and cells in healing skin wounds and, accordingly, wound healing was delayed in mice lacking NKG2D. Transcriptional activation by E2Fs is likely coordinated with posttranscriptional regulation by other stress responses. These findings suggest that cellular proliferation, as occurs in cancer cells but also other pathological conditions, is a key signal tied to immune reactions mediated by NKG2D-bearing lymphocytes.
Suramin, an Active Nonhormonal Cytotoxic Drug for Treatment of Prostate Cancer: Compelling Reasons for Testing in Patients With Hormone-Refractory Breast Cancer
Authors: Mario A. Eisenberger, Joseph A. Fontana
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Suramin, an Active Nonhormonal Cytotoxic Drug for Treatment of Prostate Cancer: Compelling Reasons for Testing in Patients With Hormone-Refractory Breast Cancer Get access Mario A. Eisenberger, Mario A. Eisenberger Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph A. Fontana Joseph A. Fontana Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 1, 1 January 1992, Pages 3–5, https://doi.org/10.1093/jnci/84.1.3 Published: 01 January 1992 Article history Received: 27 November 1991 Accepted: 02 December 1991 Published: 01 January 1992
Technique for measuring regional two-dimensional finite strains in canine left ventricle.
Authors: F J Villarreal, L K Waldman, W Y Lew
Journal: Circulation Research (1988)

We developed a technique to measure regional two-dimensional deformations in the myocardium. Three piezoelectric crystals were implanted in a triangular array in the left ventricular anterior midwall in six anesthetized dogs. Each crystal was used in a dual function, to both transmit and receive ultrasonic signals from the other two crystals. In this manner, the three segment lengths of the crystal triangle throughout the cardiac cycle were simultaneously recorded. The orientation of the crystal triangle with reference to the left ventricular long and minor axes was determined. The orientation and three segment lengths of the crystal triangle were used to calculate the circumferential strain E11, the longitudinal strain E22, the in-plane shear strain E12, and the mutually perpendicular principal strains E1 and E2. Also, the orientation of the first principal direction or the in-plane angle was determined, which was defined as the angle between the first principal direction (E1) and the circumferential direction (0 degree). This information fully describes the regional two-dimensional myocardial deformations. This technique was applied to measure regional myocardial deformations at three different left ventricular end-diastolic pressures (LVEDP) of 2 +/- 1 (mean +/- SD), 8 +/- 1, and 17 +/- 2 mm Hg. The first principal direction at end-systole was oriented away from the circumferential direction at low LVEDP (-43 +/- 21 degrees) but became progressively closer in each animal to the circumferential direction as LVEDP increased to mid (-26 +/- 18 degrees) and high (-14 +/- 13 degrees) levels. The end-systolic ratio E11/E1 was 0.6 +/- 0.2 at low LVEDP, but increased toward unity in each animal to 0.9 +/- 0.1 at mid and high LVEDP. Thus, at low LVEDP, the greatest systolic deformation occurred in a direction different from the circumferential orientation. Therefore, circumferential strain measurements (E11) significantly underestimated the greatest systolic deformation (E1). However, as LVEDP increased, the first principal direction rotated closer toward the circumferential orientation, and circumferential strain measurements adequately estimated the greatest systolic deformation. Nevertheless, the presence of significant amounts of shortening along either the longitudinal (E22) or the second principal direction (E2) in the midwall necessitated the use of the two-dimensional method. The change in end-diastolic configuration as LVEDP increased from 1 +/- 1 to 16 +/- 1 mm Hg was also examined. Unlike the end-systolic data, the end-diastolic first principal direction did not deviate significantly from the circumferential direction at any LVEDP.(ABSTRACT TRUNCATED AT 400 WORDS)
Different clinical features of aortic intramural hematoma versus dissection involving the ascending aorta
Authors: Jae-Kwan Song, Hyun-Sook Kim, Duk-Hyun Kang, Tae-Hwan Lim, Meong-Gun Song, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2001)
Monoclonal Antibody against the Ectodomain of E-Cadherin (DECMA-1) Suppresses Breast Carcinogenesis: Involvement of the HER/PI3K/Akt/mTOR and IAP Pathways
Authors: Sabine M. Brouxhon, Stephanos Kyrkanides, Xiaofei Teng, Veena Raja, M. Kerry O'Banion, Robert Clarke, Stephen Byers, Andrew Silberfeld, Carmen Tornos, Li Ma
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Although targeted therapies against HER2 have been one of the most successful therapeutic strategies for breast cancer, patients eventually developed acquired resistance from compensatory upregulation of alternate HERs and mitogen-activated protein kinase–phosphoinositide 3-kinase (PI3K)/Akt/mTOR signaling. As we and others have shown that the soluble ectodomain fragment of E-cadherin exerts prooncogenic effects via HER1/2–mediated binding and activation of downstream prosurvival pathways, we explored whether targeting this ectodomain [DECMA-1 monoclonal antibody (mAb)] was effective in the treatment of HER2-positive (HER2+) breast cancers. Experimental Design: MMTV-PyMT transgenic mice and HER2+/E-cadherin–positive MCF-7 and BT474 trastuzumab-resistant (TtzmR) cells were treated with the DECMA-1 mAb. Antitumor responses were assessed by bromodeoxyuridine incorporation, apoptosis, and necrosis. The underlying intracellular prooncogenic pathways were explored using subcellular fractionation, immunoprecipitation, fluorescence microscopy, and immunoblotting. Results: Treatment with DECMA-1 mAb significantly delayed tumor onset and attenuated tumor burden in MMTV-PyMT mice by reducing tumor cell proliferation and inducing apoptosis without any detectable cytotoxicity to mice or end-organs. In vitro treatment of MCF-7 and BT474 TtzmR cells reduced proliferation and induced cancer cell apoptosis. Importantly, this inhibition of breast tumorigenesis was due to concomitant downregulation, via ubiquitin-mediated degradation through the lysosome and proteasome pathways, of all HER family members, components of downstream PI3K/Akt/mTOR prosurvival signaling and suppression of inhibitor of apoptosis proteins. Conclusions: Our results establish that the E-cadherin ectodomain-specific mAb DECMA-1 inhibits Ecad+/HER2+ breast cancers by hindering tumor growth and inducing apoptosis via downregulation of key oncogenic pathways involved in trastuzumab resistance, thereby establishing a novel therapeutic platform for the treatment of HER2+ breast cancers. Clin Cancer Res; 19(12); 3234–46. ©2013 AACR.
Memory Impairments Associated With Postprandial Hyperglycemia and Glycemic Control
Authors: Thomas Kubiak, Norbert Hermanns, Michael Preier, Bernhard Kulzer, Thomas Haak
Journal: Diabetes Care (2004)

It was with interest that we read the study by Greenwood et al. (1), which investigated the impact of postprandial hyperglycemia on memory function in type 2 diabetic patients and demonstrated impaired memory function after carbohydrate ingestion. As they thoroughly discussed, the impact of glycemic control and transient hyperglycemia has been under investigation since the mid-1980s (2,3 …
Overexpression of Peptidyl-Prolyl Isomerase-Like 1 Is Associated with the Growth of Colon Cancer Cells
Authors: Kazutaka Obama, Tatsushi Kato, Suguru Hasegawa, Seiji Satoh, Yusuke Nakamura, Yoichi Furukawa
Journal: Clinical Cancer Research (2006)

Abstract Purpose and Experimental Design: To discover novel therapeutic targets for colon cancers, we previously surveyed expression patterns among 23,000 genes in colon cancer tissues using a cDNA microarray. Among the genes that were up-regulated in the tumors, we selected for this study peptidyl-prolyl isomerase-like 1 (PPIL1) encoding PPIL1, a cyclophilin-related protein. Results: Western blot analysis and immunohistochemical staining using PPIL1-specific antibody showed that PPIL1 protein was frequently overexpressed in colon cancer cells compared with noncancerous epithelial cells of the colon mucosa. Colony formation assay showed a growth-promoting effect of wild-type PPIL1 on NIH3T3 and HEK293 cells. Consistently, transfection of short-interfering RNA specific to PPIL1 into SNUC4 and SNUC5 cells effectively reduced expression of the gene and retarded growth of the colon cancer cells. We further identified two PPIL1-interacting proteins, SNW1/SKIP (SKI-binding protein) and stathmin. SNW1/SKIP is involved in the regulation of transcription and mRNA splicing, whereas stathmin is involved in stabilization of microtubules. Therefore, elevated expression of PPIL1 may play an important role in proliferation of cancer cells through the control of SNW1/SKIP and/or stathmin. Conclusion: The findings reported here may offer new insight into colonic carcinogenesis and contribute to the development of new molecular strategies for treatment of human colorectal tumors.
High Levels of Circulating Insulin-Like Growth Factor-I Increase Prostate Cancer Risk: A Prospective Study in a Population-Based Nonscreened Cohort
Authors: Pär Stattin, Sabina Rinaldi, Carine Biessy, Ulf-Håkan Stenman, Göran Hallmans, Rudolf Kaaks
Journal: Journal of Clinical Oncology (2004)

Insulin-like growth factor-I (IGF-I) stimulates proliferation and inhibits apoptosis in prostate cancer cells, and IGF-I has been associated with increased prostate cancer risk in some, but not all, epidemiologic studies.We extended our previous case-control study nested in the Northern Sweden Health and Disease Cohort, a population-based cohort from a region where little prostate specific antigen (PSA) screening is done. Levels of IGF-I and IGF binding protein-3 (IGFBP-3) were measured in prediagnostic blood samples from a total of 281 men who were subsequently diagnosed with prostate cancer after recruitment (median, 5 years after blood collection) and from 560 matched controls.Logistic regression analyses showed increases in prostate cancer risk with increasing plasma peptide levels, up to an odds ratio (OR) for top versus bottom quartile of IGF-I of 1.67 (95% CI, 1.02 to 2.71; Ptrend = .05), which was attenuated after adjustment for IGFBP-3 to an OR of 1.47 (95% CI, 0.81 to 2.64; P (trend) =.32). For men younger than 59 years at recruitment, OR for top versus bottom quartile of IGF-I was 4.12 (95% CI, 1.01 to 16.70; Ptrend = .002), which was significantly stronger than for men older than 59 years (P (interaction) = .006). For men with advanced cancer, OR for top versus bottom quartile of IGF-I was 2.87 (95% CI, 1.01 to 8.12; Ptrend = .10).Our data add further support for IGF-I as an etiologic factor in prostate cancer and indicate that circulating IGF-I levels measured at a comparatively young age may be most strongly associated with prostate cancer risk.
Adaptive Mitochondrial Reprogramming and Resistance to PI3K Therapy
Authors: Jagadish C. Ghosh, Markus D. Siegelin, Valentina Vaira, Alice Faversani, Michele Tavecchio, Young Chan Chae, Sofia Lisanti, Paolo Rampini, Massimo Giroda, M. Cecilia Caino, Jae Ho Seo, Andrew V. Kossenkov, Ryan D. Michalek, David C. Schultz, Silvano Bosari, Lucia R. Languino, Dario C. Altieri
Journal: JNCI Journal of the National Cancer Institute (2015)

Small molecule inhibitors of phosphatidylinositol-3 kinase (PI3K) have been developed as molecular therapy for cancer, but their efficacy in the clinic is modest, hampered by resistance mechanisms.We studied the effect of PI3K therapy in patient-derived tumor organotypic cultures (from five patient samples), three glioblastoma (GBM) tumor cell lines, and an intracranial model of glioblastoma in immunocompromised mice (n = 4-5 mice per group). Mechanisms of therapy-induced tumor reprogramming were investigated in a global metabolomics screening, analysis of mitochondrial bioenergetics and cell death, and modulation of protein phosphorylation. A high-throughput drug screening was used to identify novel preclinical combination therapies with PI3K inhibitors, and combination synergy experiments were performed. All statistical methods were two-sided.PI3K therapy induces global metabolic reprogramming in tumors and promotes the recruitment of an active pool of the Ser/Thr kinase, Akt2 to mitochondria. In turn, mitochondrial Akt2 phosphorylates Ser31 in cyclophilin D (CypD), a regulator of organelle functions. Akt2-phosphorylated CypD supports mitochondrial bioenergetics and opposes tumor cell death, conferring resistance to PI3K therapy. The combination of a small-molecule antagonist of CypD protein folding currently in preclinical development, Gamitrinib, plus PI3K inhibitors (PI3Ki) reverses this adaptive response, produces synergistic anticancer activity by inducing mitochondrial apoptosis, and extends animal survival in a GBM model (vehicle: median survival = 28.5 days; Gamitrinib+PI3Ki: median survival = 40 days, P = .003), compared with single-agent treatment (PI3Ki: median survival = 32 days, P = .02; Gamitrinib: median survival = 35 days, P = .008 by two-sided unpaired t test).Small-molecule PI3K antagonists promote drug resistance by repurposing mitochondrial functions in bioenergetics and cell survival. Novel combination therapies that target mitochondrial adaptation can dramatically improve on the efficacy of PI3K therapy in the clinic.
THE EFFECTS ON THE SKIN OF SOME NEW ADHESIVES AND LAMINATING MATERIALS. *
Authors: GEOFFREY HODGSON
Journal: British Journal of Dermatology (1960)

Journal Article THE EFFECTS ON THE SKIN OF SOME NEW ADHESIVES AND LAMINATING MATERIALS. Get access GEOFFREY HODGSON, M.B.E., M.D. GEOFFREY HODGSON, M.B.E., M.D. The Royal Infirmary, Cardiff, Glamorgan, Wales Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 3, 1 March 1960, Pages 95–104, https://doi.org/10.1111/j.1365-2133.1960.tb13853.x Published: 01 March 1960
The law looks at assisted dying
Authors: M. A. Branthwaite
Journal: Thorax (2011)

The ethical and legal aspects of suicide and assisted suicide have been the subject of vigorous debate in the recent past but the controversy is not new.This paper, loosely based on an invited lecture to the 2010 summer meeting of the British Thoracic Society, seeks to explore the dilemma by tracing the attitude of English law to medical involvement in death and dying over the last 75 years.
MiR423-5p As a Circulating Biomarker for Heart Failure
Authors: Anke J. Tijsen, Esther E. Creemers, Perry D. Moerland, Leon J. de Windt, Allard C. van der Wal, Wouter E. Kok, Yigal M. Pinto
Journal: Circulation Research (2010)

Aberrant expression profiles of circulating microRNAs (miRNAs) have been described in various diseases and provide high sensitivity and specificity. We explored circulating miRNAs as potential biomarkers in patients with heart failure (HF).The goal of this study was to determine whether miRNAs allow to distinguish clinical HF not only from healthy controls but also from non-HF forms of dyspnea.A miRNA array was performed on plasma of 12 healthy controls and 12 HF patients. From this array, we selected 16 miRNAs for a second clinical study in 39 healthy controls and in 50 cases with reports of dyspnea, of whom 30 were diagnosed with HF and 20 were diagnosed with dyspnea attributable to non-HF-related causes. This revealed that miR423-5p was specifically enriched in blood of HF cases and receiver-operator-characteristics (ROC) curve analysis showed miR423-5p to be a diagnostic predictor of HF, with an area under the curve of 0.91 (P<0.001). Five other miRNAs were elevated in HF cases but also slightly increased in non-HF dyspnea cases.We identify 6 miRNAs that are elevated in patients with HF, among which miR423-5p is most strongly related to the clinical diagnosis of HF. These 6 circulating miRNAs provide attractive candidates as putative biomarkers for HF.
Intramyocardial Transplantation of Autologous Endothelial Progenitor Cells for Therapeutic Neovascularization of Myocardial Ischemia
Authors: Atsuhiko Kawamoto, Tengis Tkebuchava, Jun-Ichi Yamaguchi, Hiromi Nishimura, Young-Sup Yoon, Charles Milliken, Shigeki Uchida, Osamu Masuo, Hideki Iwaguro, Hong Ma, Allison Hanley, Marcy Silver, Marianne Kearney, Douglas W. Losordo, Jeffrey M. Isner, Takayuki Asahara
Journal: Circulation (2003)

Background— We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia. Methods and Results— Myocardial ischemia was induced by placement of an ameroid constrictor around swine left circumflex artery. Four weeks after constrictor placement, CD31+ mononuclear cells (MNCs) were freshly isolated from the peripheral blood of each animal. After overnight incubation of CD31+ MNCs in noncoated plates, nonadhesive cells (NA/CD31+ MNCs) were harvested as the endothelial progenitor cell–enriched fraction. Nonadhesive CD31− cells (NA/CD31− MNCs) were also prepared. Autologous transplantation of 10 7 NA/CD31+ MNCs, 10 7 NA/CD31− MNCs, or PBS was performed with a NOGA mapping injection catheter to target ischemic myocardium. In a parallel study, 10 5 human CD34+ MNCs, 10 5 human CD34− MNCs, or PBS was transplanted into ischemic myocardium of nude rats 10 minutes after ligation of the left anterior descending coronary artery. In the swine study, ischemic area by NOGA mapping, Rentrop grade angiographic collateral development, and echocardiographic left ventricular ejection fraction improved significantly 4 weeks after transplantation of NA/CD31+ MNCs but not after injection of NA/CD31− MNCs or PBS. Capillary density in ischemic myocardium 4 weeks after transplantation was significantly greater in the NA/CD31+ MNC group than the control groups. In the rat study, echocardiographic left ventricular systolic function and capillary density were significantly better preserved in the CD34+ MNC group than in the control groups 4 weeks after myocardial ischemia. Conclusions— These favorable outcomes encourage future clinical trials of catheter-based, intramyocardial transplantation of autologous CD34+ MNCs in the setting of chronic myocardial ischemia.