tbuckley/cabot-search huggingface dataset:
Heart-Rate Recovery Immediately after Exercise as a Predictor of Mortality
Authors: Christopher R. Cole, Eugene H. Blackstone, Fredric J. Pashkow, Claire E. Snader, Michael S. Lauer
Journal: New England Journal of Medicine (1999)

The increase in heart rate that accompanies exercise is due in part to a reduction in vagal tone. Recovery of the heart rate immediately after exercise is a function of vagal reactivation. Because a generalized decrease in vagal activity is known to be a risk factor for death, we hypothesized that a delayed fall in the heart rate after exercise might be an important prognostic marker.For six years we followed 2428 consecutive adults (mean [+/-SD] age, 57+/-12 years; 63 percent men) without a history of heart failure or coronary revascularization and without pacemakers. The patients were undergoing symptom-limited exercise testing and single-photon-emission computed tomography with thallium scintigraphy for diagnostic purposes. The value for the recovery of heart rate was defined as the decrease in the heart rate from peak exercise to one minute after the cessation of exercise. An abnormal value for the recovery of heart rate was defined as a reduction of 12 beats per minute or less from the heart rate at peak exercise.There were 213 deaths from all causes. A total of 639 patients (26 percent) had abnormal values for heart-rate recovery. In univariate analyses, a low value for the recovery of heart rate was strongly predictive of death (relative risk, 4.0; 95 percent confidence interval, 3.0 to 5.2; P<0.001). After adjustments were made for age, sex, the use or nonuse of medications, the presence or absence of myocardial perfusion defects on thallium scintigraphy, standard cardiac risk factors, the resting heart rate, the change in heart rate during exercise, and workload achieved, a low value for heart-rate recovery remained predictive of death (adjusted relative risk, 2.0; 95 percent confidence interval, 1.5 to 2.7; P<0.001).A delayed decrease in the heart rate during the first minute after graded exercise, which may be a reflection of decreased vagal activity, is a powerful predictor of overall mortality, independent of workload, the presence or absence of myocardial perfusion defects, and changes in heart rate during exercise.
Randomized, Blinded, Placebo-Controlled Phase I Trial of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor With Filgrastim After Dose-Intensive Chemotherapy in Patients With Advanced Cancer
Authors: Russell L. Basser, John E.J. Rasko, Kerrie Clarke, Jonathan Cebon, Michael D. Green, Andrew P. Grigg, John Zalcberg, Brian Cohen, Joan O'Byrne, Dora M. Menchaca, Richard M. Fox, C. Glenn Begley
Journal: Blood (1997)
Abstract 723: Anticancer ERK kinase inhibitor screening with molecular imaging.
Authors: Lanlan Zhou, Shengliang Zhang, David T. Dicker, Alnawaz Rehemtulla, Wafik S. El-Deiry
Journal: Cancer Research (2013)

Abstract Extracellular signal-regulated kinase (ERK, also known as the 42-/44-kDa MAPK) signaling pathway controls cell growth, differentiation and survival. ERK is activated by dual phosphorylation on tyrosine and threonine residues (pERK) as a result of genetic alterations in key components of the ERK pathway or upstream activators, or in response to signals from a variety of cell surface receptors. This pro-survival pathway is often upregulated in tumors and is a target for cancer therapy. To screen for ERK inhibitors in small molecule library, an ERK reporter molecule was used to determine ERK kinase activity by measuring bioluminescence with a Xenogen IVIS Optical Imaging System. ERK kinase inhibition was confirmed with Western Blot for pERK to validate ERK reporter. Drug-like small molecule compound libraries NCI Approved Oncology Drug Set (total 2 Plates, 101 compounds) and NCI Diversity Set II (total 18 Plates, 1364 compounds) were screened with an ERK reporter expressing cell line BxPC3-MBP by using bioluminescent assay at different time points and different dosages. Then top 15 candidates were further tested for cell toxicity IC50, ERK kinase inhibition, EGFR kinase inhibition, and combinational treatment response with chemotherapy agents in normal cell MRC-5, colorectal cancer cell SW480, and non-small cell lung cancer cell H460 and Calu6. ERK kinase inhibitor candidate number 6 was found to inhibit ERK kinase activity in a dose-dependent manner and have relatively lower toxicity to normal cells than cancer cells. Clinical trials of Sorafenib (an established small molecular inhibitor of several Tyrosine protein kinases and Raf kinases) combined with Cisplatin and Etoposide on small cell lung cancer and non-small cell lung cancer showed not favorable so Etoposide was compared with its similar structure Teniposide in our combination treatment. Combinational treatments were tested here are ERK kinase inhibitor candidate/Sorafenib combined with Cisplatin and Etoposide/Teniposide. Our results demonstrated that comparing with Sorafenib, ERK kinase inhibitor candidate number 6 was more efficient in killing non-small cell lung cancer cells in combinational treatment with Teniposide and Cisplatin. This ERK kinase inhibitor candidate has shown considerable promise for further in vivo study and clinical development. Citation Format: Lanlan Zhou, Shengliang Zhang, David T. Dicker, Alnawaz Rehemtulla, Wafik S. El-Deiry. Anticancer ERK kinase inhibitor screening with molecular imaging. [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 723. doi:10.1158/1538-7445.AM2013-723
Inner speech as a forward model?
Authors: Gary M Oppenheim
Journal: Behavioral and Brain Sciences (2013)

Abstract Pickering &amp; Garrod (P&amp;G) consider the possibility that inner speech might be a product of forward production models. Here I consider the idea of inner speech as a forward model in light of empirical work from the past few decades, concluding that, while forward models could contribute to it, inner speech nonetheless requires activity from the implementers.
Abstract 194: The Golgi/ER protein p23/Tmp21 regulates PKCΔ-mediated apoptosis in prostate cancer cells
Authors: Hongbin Wang, Liqing Xiao, Marcelo G. Kazanietz
Journal: Cancer Research (2011)

Abstract Protein kinase C isozymes have prominent and specific roles in the control of apoptosis and survival of cancer cells. Activation of PKCΔ in androgen-dependent prostate cancer cell models triggers an apoptotic response that is mediated by the release of death factors and the activation of the extrinsic apoptotic cascade. We have previously established that p23/Tmp21, a member of the p24 family ER/Golgi cargo protein, physically interacts with the C1 domains in PKC isozymes and regulates the their activation. Here we found that depletion of p23/Tmp21 significantly potentiates apoptosis induced by phorbol 12-myristate 13-acetate (PMA) in LNCaP prostate cancer cells and the DNA damaging agent doxorubicin. The potentiation of the PMA effect was prevented by the pan-PKC inhibitor GF 109203X or PKCΔ RNAi depletion. Yeast two-hybrid assay revealed that the PKCΔC1a-b domain interacts with p23/Tmp21. In addition, co-localization analysis by confocal microscopy demonstrated that GFP-PKCΔ C1b domain co-localizes with p23/Tmp21 in the perinuclear region. The interaction of PKCΔ and p23/Tmp21 in LNCaP cells was also confirmed by co-immunoprecipitation. Interestingly, disruption of PKCΔ-p23/Tmp21 association by depletion of p23/Tmp21 in LNCaP cells significantly accelerated PMA-induced PKCΔ translocation to the plasma membrane and potentiates the activation of PKCΔ downstream effectors ROCK and JNK. Moreover, a mutated PKCΔ that is unable to interact with p23/Tmp21 triggered significant apoptotic effect when expressed in LNCaP cells. In summary, our data provide evidence that p23/Tmp21 acts as an anchoring protein that retains PKCΔ at the perinuclear region, thus limiting its availability for signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 194. doi:10.1158/1538-7445.AM2011-194
Breast Cancer Summits Sought To Educate Communities
Authors: L. F. Anderson
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Breast Cancer Summits Sought To Educate Communities Get access Linda F. Anderson Linda F. Anderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 4, 15 February 1995, Pages 252–253, https://doi.org/10.1093/jnci/87.4.252 Published: 15 February 1995
Abstract 760: Sensitizing tumors to chemotherapy by inhibition of gamma-glutamyl transpeptidase
Authors: Stephanie LaChapelle, Paul F. Cook, Marie H. Hanigan
Journal: Cancer Research (2010)

Abstract Tumors that express the cell surface enzyme gamma-glutamyl transpeptidase (GGT) have increased resistance to chemotherapy and radiation. GGT cleaves the gamma-glutamyl bond of extracellular glutathione, initiating the cleavage of glutathione into glutamate, cysteine and glycine. Glutathione can not be taken up intact by tumor cells. Cleavage of extracellular glutathione increases the supply of cysteine to the cell, which is essential to increasing intracellular glutathione levels. Glutathione detoxifies chemotherapy drugs, and elevated levels of intracellular glutathione can block apoptosis. We are developing inhibitors of GGT that can be used to sensitize tumors to therapy. The standard assay for GGT activity uses p-nitroanilide derivatives as substrates, millimolar concentrations of dipeptides as acceptors and is buffered at pH 8.6. Under these assay conditions several groups of investigators have shown that GGT cleaves the gamma-glutamyl bond of the substrate and transfers the gamma-glutamyl group to an acceptor by a Ping-Pong mechanism. However, the standard assay for GGT activity does not measure the reaction catalyzed by GGT in vivo. We have assayed GGT activity under physiologic conditions. We have found that some compounds that inhibit GGT activity in the standard reaction do not inhibit under physiologic conditions. Our data reveal that, at physiologic pH and osmolarity with reduced concentrations of acceptor, the enzyme does cleave the gamma-glutamyl bond by a Ping-Pong mechanism, but hydrolysis of the intermediate of the gamma-glutamyl enzyme intermediate is significant, and competition between water and the peptide acceptor for the intermediate makes it appear Sequential. Several compounds that inhibit GGT in the standard assay actually accelerate activity as the concentration of the acceptor is reduced to physiologic levels. To identify inhibitors that are optimized for clinical use, we have developed an assay that evaluates GGT cleavage of glutathione, the physiologic substrate, at physiologic pH and osmolarity. We are using our previously reported inhibitor OU749 and other lead compounds to further characterize the physiologic GGT reaction and to identify essential substructural components for inhibition of GGT activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 760.
THU0492-HPR The effectiveness of shiatsu on pain, sleep quality and balance confidence of fibromyalgia patients: A controlled clinical trial
Authors: S.L.K. Yuan, A.A. Berssaneti, A.P. Marques
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia is a painful musculoskeletal disorder that compromises function and quality of life. Studies show that no single treatment is completely effective in all patients and many of them seek complementary and alternative medicine. However its evidence is still insufficient. <h3>Objectives</h3> This clinical trial aimed to verify the effectiveness of Shiatsu (Japanese massage technique) in the improvement of pain, sleep quality and balance confidence of fibromyalgia patients. <h3>Methods</h3> This study involved 34 women aged 33 to 62 years, divided into two groups: Shiatsu Group (SG; n=17), which received 16 sessions of Shiatsu lasting 50 minutes, twice a week, and Control Group (CG; n=17), who received educational guidance through a booklet. Both groups were evaluated before and after 8 weeks. The following instruments were used: Visual Analog Pain Scale, Dolorimeter, Pittsburgh Sleep Quality Index and Activities-Specific Balance Confidence Scale. Intergroup statistical analysis was performed using the t-test for data sets with normal distribution and the same variance and Mann-Whitney Rank Sum Test for data sets without normal distribution or equal variance. The significance level was α=0.05. <h3>Results</h3> At baseline, both groups were similar for all variables. After eight weeks, SG showed statistically significant improvement in pain (p=0.015), tender point pain threshold (p&lt;0,001) and sleep quality (p=0.018), when compared with the CG. There was no statistically significant difference for balance confidence between groups. <h3>Conclusions</h3> The results indicate that the Shiatsu technique is effective in improving pain, tenderness and sleep quality in fibromyalgia patients. <h3>References</h3> Sarzi-Puttini P, Buskila D, Carrabba M, Doria A, Atzeni F. Treatment Strategy in Fibromyalgia Syndrome: Where Are We Now? Semin Arthritis Rheum. 2008;37(6):353-65. Jones KD, Horak FB, Winters-Stone K, Irvine JM, Bennett RM. Fibromyalgia is associated with impaired balance and falls. J Clin Rheumatol. 2009;15(1):16-21. Baranowsky J, Klose P, Musial F, Häuser W, Dobos G, Langhorst J. Qualitative systemic review of randomized controlled trials on complementary and alternative medicine treatments in fibromyalgia. Rheumatol Int. 2009;30(1):1-21. <h3>Disclosure of Interest</h3> None Declared
1013 HISTOLOGICAL SUB-CLASSIFICATION OF CIRRHOSIS IS USEFUL FOR PREDICTION OF RECURRENCE AFTER CURATIVE RESECTION OF HBV-RELATED HEPATOCELLULAR CARCINOMA
Authors: S.U. Kim, K.S. Jung, S.R. Lee, J.Y. Park, D.Y. Kim, S.H. Ahn, C.Y. Chon, G.H. Choi, K.S. Kim, J.S. Choi, Y.N. Park, K.-H. Han
Journal: Journal of Hepatology (2012)
Intrathoracic Splenosis
Authors: Babak Mahmoudian, Reza Javadrashid, Ashraf Fakhrjoo
Journal: Clinical Nuclear Medicine (2014)

Scanning using a somatostatin receptor analog such as 99mTc-EDDA/HYNIC-TOC has sensitivity and specificity similar to those of 18FDG-PET, which has high accuracy in the characterization of a solitary pulmonary nodule (SPN). We describe a 63-year-old man with well-defined SPN in the left lung on chest x-ray and CT scan. Whole-body scanning and chest SPECT were performed with 99mTc-EDDA/HYNIC-TOC for the characterization of SPN. Abnormal focal increased radiotracer uptake in the left hemithorax was detected. In addition, no spleen activity was observed in the anatomical location. Cytopathologic evaluation of SPN revealed splenosis.
CARDIOVASCULAR OUTCOMES WITH AN INHALED LONG-ACTING BETA AGONIST AND CORTICOSTEROID IN PATIENTS WITH MODERATE CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND HEIGHTENED CARDIOVASCULAR RISK: THE SUMMIT TRIAL
Authors: Robert D. Brook, Julie Anderson, Peter Calverley, Bartolome Celli, Courtney Crim, Martin Denvir, Sheldon Magder, Fernando Martinez, Sanjay Rajagopalan, Joergen Vestbo, Julie Yates, David Newby
Journal: Journal of the American College of Cardiology (2016)
PTU-093 An Evaluation Of An Ibd Advice Service: Is It Meeting Its Service Aims?
Authors: G Collins, M Sastrillo, J Duncan
Journal: Gut (2014)

<h3>Introduction</h3> The provision of a dedicated and accessible IBD advice service (AS) is a key element of IBD management and, often, the responsibility of the Advanced, or specialist, IBD Nurse according to the N-ECCO Consensus statements. UK IBD Standards require IBD patients to have rapid access to specialist advice before the end of the next working day (EONWD). Our AS aims to provide timely access to clinical advice, support and acts as a point of contact to co-ordinate the patient journey. We evaluated if our advice service was meeting these goals. <h3>Methods</h3> Over a 5 week period (23 working days) during October and November 2013, all contacts to the AS of a central London tertiary IBD service were recorded. Patients either called and left a message on an answering machine, or emailed a dedicated email address. Two experienced IBD CNS’ collected data during each encounter. This included demographics of gender, age, and diagnosis; the format of contact (phone/email); if a medical opinion (IBD specialist or IBD registrar/fellow) was sought; time to response, and amount of time spent on each contact. The content of the encounter (administrative, clarification, a new query, or a symptomatic change/flare) was documented along with the response (administrative, information, results, treatment changes, medical decision), and the follow up required for the patient (routine, earlier or urgent outpatient appointment, or hospital admission/presentation to AandE). <h3>Results</h3> 262 contacts were made to the AS. 4 could not be re-contacted and 23 had missing data, leaving 235 complete encounters for analysis, of which 3 enquiries were non-IBD related. Those who contacted the AS were predominantly female (148/235, 62.98%), between 26–35 (97/235, 41.28%), with a diagnosis of Crohn’s Disease (160/235, 68.09%), the latter reflecting the tertiary nature of our IBD service. 99.15% (233/235) of contacts were replied to by EONWD, with 38.29% (90/235) answered within 12 h. The majority of contacts (85.11%) were for clinical reasons with 14.89% administrative (35/235). 51/235 (21.70%) pertained to flares. 88.94% (209/235) were autonomously handled by the IBD CNS though IBD Consultant/Fellow support was required in 26 cases. AandE presentation was recommended to 2 patients (2/235, 0.85%) and 25(10.64%) had their outpatient appointment brought forward, meaning the vast majority were clinically managed without the need for additional outpatient review. <h3>Conclusion</h3> Our IBD advice service provides patients with rapid access to specialist advice, symptom management and disease-specific information, meeting UK national standards. The IBD CNS’ expertise means clinical enquiries can be effectively managed whilst avoiding additional, unnecessary burden to the patient and to outpatient clinics. <h3>Disclosure of Interest</h3> None Declared.
Occurrence of Rheumatic-like Subcutaneous Nodules without Evidence of Joint or Heart Disease
Authors: Angelo Taranta
Journal: New England Journal of Medicine (1962)

SUBCUTANEOUS nodules have long been known to occur in rheumatic fever and in rheumatoid arthritis. In both diseases their presence has been considered an indication of severity.1 2 3 It was with interest, therefore, that we observed, eight years ago, a child with subcutaneous nodules who, far from having a particularly severe form of rheumatic fever or rheumatoid arthritis, had no other signs of either disease. In the ensuing years two reports called the attention of American pathologists to similar cases,4 , 5 but even now few clinicians are aware that lesions indistinguishable from rheumatic or rheumatoid nodules can occur in otherwise healthy subjects. . . .
Abstract 639: Measuring PI3K and MAPK pathways inhibition, comparison between conventional IHC and AQUA-TMA technology
Authors: Ludmila Prudkin, Violeta Serra, Claudia Aura, José Jimenez, Maurizio Scaltriti, José Baselga
Journal: Cancer Research (2010)

Abstract The incorporation of molecular biomarkers to assess therapy efficacy is crucial in both preclinical and clinical phases of drug development. New generation targeted therapy requires sensitive and robust analyses that accurately measure up- or down-regulation of specific pathways in response to a given therapeutic strategy. Paraffin embedded tissue is the sample commonly available in the clinic, and immunohistochemistry (IHC) has become the gold standard for biomarker detection. Although the reproducibility of this method has improved over time, IHC remains a semi-quantitative and subjective evaluation (H-score) of both intensity and expression extent of a given protein. These drawbacks can be by-passed by using automated quantitative analysis-tissue microarray (AQUA-TMA) technology. This platform analyzes double immunofluorescence (dIF) images and provides precise and objective staining quantifications using the AQUAnalysis software. In this work we show a comparison between conventional IHC and AQUA-TMA technology in assessing the efficacy of Hsp90 inhibition, PI3K/mTOR inhibition and Akt inhibition in a HER2-driven breast cancer xenograft model measuring a number of biomarkers. Both IHC and dIF techniques have been performed on TMAs and several molecular markers have been evaluated. Specifically, we have measured the levels of HER2, AKT and MAPK total proteins as well as phosphorylation of AKT, MAPK, PRAS40, p70-S6K and S6RP in response to the aforementioned therapies. Moreover, since the AQUAnalysis software also recognizes cellular and sub-cellular compartments of fluorescent signals, we investigated FOXO nuclear translocation. Our results show that the AQUA technology adds more accuracy than IHC to the assessment of the studied biomarkers. TMAs are readily scanned and analyzed by the software, and the quantification values provided by the system are directly used for statistical analysis. Our work suggests that, although IHC and H-Score is the current method of evaluation, an accurate and unbiased measurement of molecular markers using the AQUA-TMA platform can improve the assessment of target inhibition in both preclinical and clinical settings. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 639.