tbuckley/cabot-search huggingface dataset:
Why is talking about dying such a challenge?
Authors: K. Boyd, S. A. Murray
Journal: BMJ (2014)

Much more needs to be done to encourage the conversation 

In May, Stephen Sutton died at the age of 19 years from bowel cancer. His love of life and extensive fundraising showed everyone how to live life to the full, even when dying. Death is universal. But most patients and doctors still struggle to deal with the challenges posed by deteriorating health and thinking about dying. How and where people die depends not only on their disease but on their circumstances, options, choices, expectations, values, and beliefs. Open, early discussions about what matters when people are dying are vital if we are to act on the growing list of policies, good practice guidance, and recommendations.

A recent survey of 2055 British adults commissioned by the health promoting palliative care organisation “Dying Matters” found that about half of those with a partner knew about their partner’s end of life wishes. Just 6% had written down their own preferences despite sustained campaigns to encourage public and professional engagement in advance care planning. A parallel study found some improvement in the proportion of GPs who had initiated a conversation with patients about end of life care (75% in 2014 v 65% in 2012).1 The timing of these discussions was not reported, but a Scottish primary care study found that patients with cancer or other advanced illnesses were being identified for a palliative care …
Abstract P4-06-08: Clinical utility of functional analysis of FGFR kinase family for selecting patients who may benefit from FGFR inhibitors
Authors: N Hoe, J Zhou, C Kuy, K Jin, R Srikrishnan, A Soundararajan, Y Ma, X Liu, S Singh
Journal: Cancer Research (2012)

Abstract Background: Fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases (RTKs) are currently under investigation as therapeutic targets for the treatment of breast cancer. Members of this kinase family have been associated with breast cancer progression and resistance to current therapeutics. FGFR1 amplifications range from 7.5–17% in breast cancers and are associated with a shorter overall survival. FGFR1 amplified cell lines drive activation of AKT, ERK, and RSK and are highly sensitive to FGFR1 inhibition, suggesting an oncogenic addiction to FGFR1. FGFR2 is activated in lapatinib-resistant, HER2-positive cells. Likewise, FGFR3 expression levels are elevated in tamoxifen-resistant, ER positive patients. FGFR 4 overexpression correlated with poor response to chemotherapy due to activation of MAPK and increase in B-cell lymphoma extra large (BCL-XL) levels. Using an immuno-microarray system, this study seeks to determine FGFR signal transduction pathway modulation post FGFR inhibitor treatment in breast cancer cell lines expressing varying levels of FGFR1, 2, 3 or 4. Method: FGFR 1, 2, 3, and 4 amplified cell lines (MDA-MB-134VI (KRAS), SNU16, RT112, and MDA-MB-453) were treated with varying dosages (1, 10, 100, and 1000nM) of several FGFR inhibitors (AZD4547 (pan FGFR), PD173074 (FGFR1,3) and Ponatinib-AP24534 (FGFR1)) either in presence or absence of corresponding FGF (FGF1, FGF7, FGF9, and FGF19) stimulation. Expression and activation of FGFR 1, 2, 3, and 4 and downstream signaling proteins FRS2, AKT, ERK, MEK, and RSK were measured utilizing a proximity based immuno-microarray. Results: FGFR1, 2, 3, 4 protein expression was detected in each of the corresponding four FGFR1, 2, 3, 4 amplified cell lines. Total protein levels remained unchanged with or without FGFs stimulation. Levels of FGFR1 phosphorylation increased 5 folds in MDA-MB-134VI stimulated with FGF1. FGFR2 and FGFR3 activation increased by 2–3 folds in SNU16 and RT112 stimulated with FGF7, and FGF9 respectively. FGFR4 activation levels in MDA-MB-453 remained unchanged due to Y367C mutation. ERK was activated in both FGF1 stimulated and unstimulated group in MDA-MB134 due to the KRAS mutation. RSK activation increased in both SNU16 and RT112 when stimulated with FGF7, and FGF9 respectively. FGFR inhibitors treated data analysis is currently in progress and will be presented. Conclusion: We have demonstrated utility of specific FGFR analysis using well defined model systems. FGFR- profiling should be considered during the clinical work-up in order to select patients who may benefit from regimen containing specific FGFR inhibitors. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-08.
Hospitals in Germany must do more to procure organs, says report
Authors: Annette Tuffs
Journal: BMJ (2005)

Hospital managers in Germany need to be reminded of their obligations to find organs for transplantation, says a parliamentary report.

The report, Advancement of Organ Donation , comes after a series of formal written questions from opposition parties into the state of organ donation in Germany. It admits, however, that participating in organ donation programmes can leave hospitals out of pocket, because the intensive care costs are often not fully covered.

At the moment only 40% of Germany's 1379 hospitals with intensive care beds report potential organ donors to the Deutsche …
Abstract 784: Prevalence, phenotype and prognostic significance of IL-17-producing cells infiltratinghuman colorectal cancers
Authors: Francesca Amicarella, Inti Zlobec, Manuele Giuseppe Muraro, Junyi Han, Xaver Huber, Markus Zuber, Michel Adamina, Daniel Oertli, Alessandro Lugli, Luigi Terracciano, Paul Zajac, Giulio Cesare Spagnoli, Giandomenica Iezzi
Journal: Cancer Research (2011)

Abstract Background: Lymphocytic infiltration is known to be associated with a favourable prognosis in human colorectal cancer (CRC). In particular, the presence of CD8+ T cells and, unexpectedly, of Foxp3+ regulatory T cells, has been found to be associated with improved patient survival. Recent evidence suggests that IL-17 and T helper (Th) 17 cells might also have an impact on anti-tumour immune responses. We have investigated prevalence, phenotype and prognostic significance of IL-17-producing cells in human CRC. Material and Methods: IL-17 expression was evaluated by immunohistochemistry on a tissue micro-array (TMA) including 1420 cases of primary CRC with full clinico-pathological data. Furthermore, gene expression levels were assessed on CRC tissues by quantitative PCR. Finally, in order to characterize the phenotype of IL-17-positive cells, expression of IL-17, in combination with that of specific surface molecules, was analyzed on freshly excised CRC specimens by flow cytometry. Results: Frequencies of IL-17-producing cells, as well as IL-17 gene expression levels were significantly increased in tumour tissues as compared to autologous normal mucosa. IL-17-producing cells isolated from clinical specimens were exclusively comprised within the lymphocyte population and expressed CD4, but not CD8, and surprisingly, Foxp3 molecules. Accordingly, mRNA levels of genes encoding for cytokines favouring IL-17 acquisition by Foxp3+ T cells, including IL-6, IL-1beta, TGF-beta and IL-23, were found more elevated in CRC tissues as comparing to corresponding healthy mucosa. High infiltration by IL-17 producing cells significantly correlated with low T and N stages, and, most importantly, with prolonged survival time in mismatch repair (MMR)- proficient, but not-deficient CRC. Moreover, the simultaneous CRC-infiltration by IL-17+ and Foxp3+ cells was significantly associated with improved survival in both MMR-proficient and -deficient tumours. Conclusions: Our data suggest that IL-17 produced by tumour-infiltrating either CD4+ or Foxp3+ cells may promote a benign clinical outcome in CRC. 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 784. doi:10.1158/1538-7445.AM2011-784
CONCERNING THE SURFACES OF CELLS OF STAPHYLOCOCCUS PYOGENES
Authors: Theodore Sall, Stuart Mudd, James Taubler
Journal: The Journal of Experimental Medicine (1961)

A strain of pathogenic Staphylococcus aureus, grown under special conditions, accumulates extracellular metabolites about the bacterial cells. This phenomenon may simulate, but is differentiable from, the capsulation of, for instance, the mucoid "Smith" strain. The special nutrient requirements, namely lactose, mannitol, vitamin, and gelatin containing medium, promote the production and accumulation about the cells of, in particular, soluble coagulase. A mutant of this parent strain, deficient in capacity to elaborate soluble coagulase and fibrinolysin, does not accumulate metabolites about its cells, even under the special growth conditions. To avoid confusing this phenomenon, which at least in vitro is essentially artifactitious, with true capsulation, we suggest the term pseudocapsulation.
The Accuracy of Drug Information From Pharmaceutical Sales Representatives
Authors: Michael G. Ziegler
Journal: JAMA (1995)

<h3>Objective.</h3> —To provide quantitative data about the accuracy of the information about drugs presented to physicians by pharmaceutical sales representatives. <h3>Design.</h3> —One hundred six statements about drugs made during 13 presentations by pharmaceutical representatives were analyzed for accuracy. Statements were rated inaccurate if they contradicted the 1993<i>Physicians' Desk Reference</i>or material quoted or handed out by the sales representative. <h3>Setting.</h3> —University teaching hospital. <h3>Results.</h3> —Twelve (11%) of 106 statements about drugs were inaccurate. All 12 inaccurate statements were favorable toward the promoted drug, whereas 39 (49%) of 79 accurate statements were favorable (<i>P</i>=.005). None of 15 statements about competitors' drugs were favorable, but all were accurate, significantly (<i>P</i>&lt;.001) differing from statements about promoted drugs. In a survey of 27 physicians who attended these presentations, seven (26%) recalled any false statement made by a pharmaceutical representative, and 10 (37%) said information from the representatives influenced the way they prescribed drugs. <h3>Conclusions.</h3> —Eleven percent of the statements made by pharmaceutical representatives about drugs contradicted information readily available to them. Physicians generally failed to recognize the inaccurate statements. (<i>JAMA</i>. 1995;273:1296-1298)
457. Reverse Transcriptase Deficient Retroviral Vectors for Transient Cell Modification
Authors: Melanie Galla, Axel Schambach, Elke Will, Christopher Baum
Journal: Molecular Therapy (2006)

Short-term, reversible expression of foreign proteins could be useful to modify cell fate. We have previously shown that retroviral vector mutants that are unable to initiate reverse transcription of their plus-stranded mRNA genomes mediate transient and highly efficient delivery of the site specific recombinase Cre into human and mouse fibroblasts (Galla et al., Mol Cell 2004). Cre protein activity was detected in >95% of target cells with a single treatment. Cre activity was particle-mediated and required the retroviral mRNA packaging signal as well as the expression of both Gag and Env in the packaging cell. Furthermore we could exclude plasmid contamination and Cre protein transduction as the underlying mechanisms for this mode of Cre delivery. Our data thus suggest that retrovirally delivered mRNA serves as an immediate translation template if not being reverse transcribed. When delivering the Sleeping Beauty (SB) transposase (cooperation with Z. Ivics, Berlin) by this approach, RT-deficient retroviral vector mutants were sufficient to mediate transposition of transfected plasmids containing transposon DNA. However, the efficiency of stable integration was only 3-fold above background levels, suggesting that the timing and/or expression levels have to be improved. Side-by-side comparison with the delivery of episomal DNA by lentiviral vectors revealed that RT-deficient retroviral mutants express foreign proteins for a much shorter duration (max. 4-5 days in replicating cells as opposed to >7 days for episomal lentiviral vectors) and lower levels (one to two orders of magnitude below the activity provided by episomal lentiviral vectors). As many receptor molecules require relatively low levels of expression to confer biological effects, we tested RT-deficient retroviral vectors to deliver the sialomucin CD34 or the murine cationic acid transporter mCAT-1, which serves as the receptor for the ecotropic murine leukemia virus. More than 80% of the exposed cells could be transduced following a single exposure to RT-deficient vectors encoding these receptors, and mCAT-1 expression conferred susceptibility of Jurkat cells to transduction with retroviral or lentiviral vectors pseudotyped with the murine ecotropic envelope protein. We conclude that RT-deficient retroviral vectors hold great promise for applications where low and transient expression of proteins achieves striking biological effects.
The Strength of T Cell Receptor Signal Controls the Polarization of Cytotoxic Machinery to the Immunological Synapse
Authors: Misty R. Jenkins, Andy Tsun, Jane C. Stinchcombe, Gillian M. Griffiths
Journal: Immunity (2009)

Killing by cytotoxic T lymphocytes (CTLs) is mediated by the secretion of lytic granules. The centrosome plays a key role in granule delivery, polarizing to the central supramolecular activation complex (cSMAC) within the immunological synapse upon T cell receptor (TCR) activation. Although stronger TCR signals lead to increased target cell death than do weaker signals, it is not known how the strength of TCR signal controls polarization of the centrosome and lytic granules. By using TCR transgenic OT-I CTLs, we showed that both high- and low-avidity interactions led to centrosome polarization to the cSMAC. However, only high-avidity interactions, which induced a higher threshold of intracellular signaling, gave rise to granule recruitment to the polarized centrosome at the synapse. By controlling centrosome and granule polarization independently, the centrosome is able to respond rapidly to weak signals so that CTLs are poised and ready for the trigger for granule delivery.
Barefoot doctors and the medical pyramid.
Authors: A J Smith
Journal: BMJ (1974)

China is still a predominantly rural country and the key figures in a decentralized pyramidal rural system of medical responsibility are farm workers who have been given basic medical training.  They give simple medical treatment or advice but they also continue to do their former agricultural work.  Their main duties are in health education and preventive medicine.  Generally their training program consists of a basic 3 month course at the commune or county hospital followed by periods of further training of 1 to 3 months in later years and augmented by teaching from mobile health teams or urban doctors who visit the rural areas.  Commune health care consists of health stations for production brigades and a commune hospital which offers a fairly wide range of treatments for common or recurrent disorders staffed by medical specialists.  Medical problems too complex for commune hospital staff are referred to the county hospital.  There are more than 2000 counties in China each of which has a hospital ranging in size between 100 and 300 beds.  The medical pyramid provides not just a hierarchy of specialization of treatment but also a hierarchy of medical training.  The rural health workers and their urban counterparts--the factory health workers at the bottom have only a rudimentary education; the commune hospital staff roughly parallel general practitioners and the specialists at the top have undergone extensive training.  The traditional physicians responsible for a vast amount of primary care provide China with many doctors with no ambition for urban practice.  This situation may change however as fewer recent medical school graduates have been educated in traditional medical colleges and may specialize.
Laser Fibre Deterioration and Loss of Power Output During Photo-Selective 80-W Potassium-Titanyl-Phosphate Laser Vaporisation of the Prostate
Authors: Thomas Hermanns, Tullio Sulser, Markus Fatzer, Martin K. Baumgartner, Julien M. Rey, Markus W. Sigrist, Hans-Helge Seifert
Journal: European Urology (2008)
Are Nonhuman Primates Good Models for SARS?
Authors: Robert J Hogan
Journal: PLoS Medicine (2006)

Because of the nature of the analysis used in this study [1], no conclusion is possible.There are plenty of examples in the literature demonstrating the "ecological fallacy".Studies such as this have very little utility other than to generate hypotheses.I tend to think that this association is a marker for greater recognition and treatment for depression.However, it's a brave epidemiologist who would draw any conclusions at all from an ecological association such as this where the outcome is relatively rare.
Development and preliminary validation of a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis
Authors: Clara Malattia, Maria Beatrice Damasio, Angela Pistorio, Maka Ioseliani, Iris Vilca, Maura Valle, Nicolino Ruperto, Stefania Viola, Antonella Buoncompagni, Gian Michele Magnano, Angelo Ravelli, Paolo Tomà, Alberto Martini
Journal: Annals of the Rheumatic Diseases (2010)

Objectives To develop and validate a paediatric-targeted MRI scoring system for the assessment of disease activity and damage in juvenile idiopathic arthritis (JIA). To compare the paediatric MRI score with the adult-designed. Outcome Measures in Rheumatology Clinical Trials—Rheumatoid Arthritis MRI Score (RAMRIS), whose suitability for assessing growing joints was tested. Methods In 66 patients with JIA the clinically more affected wrist was studied. Thirty-nine patients had a 1-year MRI follow-up. Two readers independently assigned the paediatric score and the RAMRIS to all studies. Validation procedures included analysis of reliability, construct validity and responsiveness to change. A reduced version of the bone erosion score was also developed and tested. Results The paediatric score showed an excellent reproducibility (interclass correlation coefficient &gt;0.9). The interobserver agreement of RAMRIS was moderate for bone erosions and excellent for bone marrow oedema (BMO). The paediatric score and RAMRIS provided similar results for construct validity. The responsiveness to change of the paediatric score was moderate for synovitis and bone erosion, and poor for BMO and did not improve when RAMRIS was applied. The reduced version of the bone erosion was valuable for the assessment of joint damage, and provided time-saving advantages. Conclusion The results demonstrate that the paediatric MRI score is a reliable and valid method for assessing disease activity and damage in JIA. Unexpectedly, the RAMRIS provides acceptable suitability for use in the paediatric age group. Further work, especially in a longitudinal setting, is required before defining the most suitable MRI scale for assessing growing joints.
Abstract C52: Semi-high-throughput whole-animal bioimaging assay identifies novel players in prostate cancer progression
Authors: Veerander Paul Singh Ghotra, Shuning H.E, Hans De Bont, H.P. Spaink, Bob Van de Water, B. Ewa Snaar Jagalska, Erik H.J. Danen
Journal: Cancer Research (2012)

Abstract Although genetic mouse models for cancer and human tumor cell xenotransplantation models in rodents remain essential, such systems are costly, slow, and not amenable to high-throughput assays for cancer drug target discovery. There is a clear need to develop fast, semi-automated in vivo systems for medium to high-throughput screening applications in preclinical target discovery and lead compound identification. In this study, we developed an automated, semi-high throughput, noninvasive and quantitative platform for imaging one critical aspect of cancer progression, namely tumor cell dissemination, in a zebrafish xenotransplantation model. This is the first semi-automated whole organism based bio-imaging assay of tumor progression in a vertebrate. We have used this platform to screen for prostate cancer relevant drug and gene targets, and have identified novel regulators of prostate cancer dissemination. Using 3D in vitro invasion assays, we show a critical role for these molecules in prostate cancer migration strategies. Further validation of these targets is underway in mouse models and human cancer specimens. Citation Format: Veerander Paul Singh Ghotra, Shuning H.E., Hans De Bont, H.P. Spaink, Bob Van de Water, B. Ewa Snaar Jagalska, Erik H.J. Danen. Semi-high-throughput whole-animal bioimaging assay identifies novel players in prostate cancer progression [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C52.
Abstract C18: A new IGF-I-regulated micronutrient carrier in cancer cells
Authors: Katie O'Callaghan, Veronica Ayllon, Jean O'Keeffe, Yanru Wang, Orla Cox, Gary Loughran, Michael Forgac, Rosemary O'Connor
Journal: Cancer Research (2009)

Abstract Cancer cells are dependent on a continuous supply of nutrients to maintain cell proliferation and migration. Nutrients are acquired through transporters whose transcription, trafficking, and degradation are tightly regulated by growth factors, especially through activity of the Insulin/IGF-I-activated PI3K/mTOR signalling pathway. The intracellular trafficking of nutrient transporters requires an acidic endosomal pH that is maintained by the Vacuolar H+ ATPase (V-ATPase) proton pump. Recent studies have indicated a role for V-ATPase activity in cancer cells, but how this is regulated is not known. We recently isolated a series of new IGF-I-regulated genes whose expression is associated with cellular transformation (1, 2). Among these was a previously uncharacterized endosomal protein, which we determined associates with the V-ATPase, and which we called EVA. This protein was separately identified in C. elegans as a member of a family of heme transporters (HRG-1) that control heme homeostasis (3). We found that EVA is present throughout the endosome compartments; in early, recycling, and late endosomes, but not in lysosomes. Upon nutrient withdrawal EVA traffics to the plasma membrane. EVA interacts with the c subunit of the V-ATPase and enhances V-ATPase activity in isolated yeast vacuoles. Suppression of EVA expression increases endosomal pH and reduces V-ATPase holoenzyme assembly. This is accompanied by decreased migration, decreased transferrin receptor trafficking, decreased cellular heme uptake, and cell death. Over-expressed EVA enhances cellular heme uptake in a V-ATPase-dependent manner. We conclude that EVA/HRG-1 regulates V-ATPase-dependent acidification of endosomes necessary for trafficking of heme receptors as well as for heme transport within endosomes. Our data suggest that IGF-I induces expression of this micro-nutrient transporter to facilitate the enhanced metabolic requirements of cancer cells. Citation Information: Cancer Res 2009;69(23 Suppl):C18.