tbuckley/cabot-search huggingface dataset:
Validation and comparison of CAM-ICU and ICDSC in mild and moderate traumatic brain injury patients
Authors: Anne Julie Frenette, Emmanuel R Bebawi, Louis C Deslauriers, Andrée-Anne L Tessier, Marc M Perreault, Marie-Soleil Delisle, Jean-Claude Bertrand, Monique Desjardins, Philippe Rico, Kosar Khwaja, Lisa D Burry, Francis Bernard, David R Williamson
Journal: Intensive Care Medicine (2015)
Abstract B05: Assessing and removing biophysical barriers to treatment
Authors: Kathleen E. DelGiorno, Markus Carlson, Paolo P. Provenzano, Scott Brockenbough, Sunil R. Hingorani
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDA) is a confounding cancer with a penchant for metastasis and resistance to therapy. Cell autonomous events, such as mutations in the Kras proto-oncogene, are essential for the initiation and maintenance of PDA; however non-malignant cells as well as non-cellular components have been shown to contribute to tumor growth, immunosuppression, and chemotherapeutic resistance. The stromal compartment can comprise more than 80% of tumor content and is characterized by a dynamic and deregulated extracellular matrix (ECM). In addition to a role in tissue structure, the ECM provides biophysical and biochemical cues that determine cell responses. PDA presents its own characteristic ECM signature including large deposits of the negatively charged glycosaminoglycan (GAG) hyaluronan (HA), as well as fibrillary collagens which increases matrix stiffness. We have previously demonstrated that high levels of HA in PDA contribute to extraordinary interstitial fluid pressures (IFP) and vascular collapse. We show here that IFP is comprised of both freely mobile and immobile fluid phases. Due to its highly charged nature, HA binds large amounts of water to create an immobile-fluid phase with a significant swelling pressure. This pressure is not detected by conventional methods that can measure only free fluid pressure. The swelling pressure stresses abundant collagen fibrils which contract through cellular efforts to maintain homeostasis, further contributing to IFP. Targeting HA through systemic administration of pegylated hyaluronidase (PEGPH20) liberates the immobile fluid phase and dramatically reduces IFP, increasing vessel patency and bioavailability of systemically delivered agents. We present results on the effects of targeting additional ECM components and signaling pathways to help remove biophysical barriers to chemotherapeutic access. We also compare the abilities of different methodologies to measure interstitial pressures associated with the distinct fluid phases in a variety of experimental contexts. Citation Format: Kathleen E. DelGiorno, Markus Carlson, Paolo P. Provenzano, Scott Brockenbough, Sunil R. Hingorani. Assessing and removing biophysical barriers to treatment. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B05.
Mortality Risk in Symptomatic Patients With Nonobstructive Coronary Artery Disease
Authors: Fay Y. Lin, Leslee J. Shaw, Allison M. Dunning, Troy M. LaBounty, Jin-Ho Choi, Jonathan W. Weinsaft, Sunaina Koduru, Millie J. Gomez, Augustin J. Delago, Tracy Q. Callister, Daniel S. Berman, James K. Min
Journal: Journal of the American College of Cardiology (2011)
A novel dendritic cell subset supporting the concept of tumor immunoediting: IFN producing Killer Dendritic cell (IKDC)
Authors: Laurence Zitvogel, Julien Taieb, Nathalie Chaput, Cédric Menard, Lionel Apetoh, Evelyn Ullrich, Mathieu Bonmort, Thomas Tursz, Graça Raposo, Hideo Yagita, Bernard Ryffel, Guido Kroemer
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4874 

IFNγ is a key immunomodulator pivotal in the host defense against tumor progression. Pionnering studies have demonstrated that IFNγ mediated-signaling pathways are critical against tumor development in recombination activation gene deficient mice. Here we show that the main source of IFNγ is not the conventional NK cell but a subset of B220+Ly6C- dendritic cells that are atypical in thus far that they express NK cell surface molecules (Dx5, NK1.1, NKG2D, Ly49). They represent 1% of splenic CD11c+ cells in naive animals, can be expanded by 5 fold by immunotherapy combining c-kit tyrosine kinase inhibitors and IL-2 or Flt3L and traffick into tumor beds where they constitute up to 20% of tumor infiltrating CD11c+. Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220+NK1.1+ dendritic cells secrete high levels of IFNγ and mediate TRAIL-dependent tumor cell lysis. During therapy with imatinib mesylate and IL-2, tumor regression depends on TRAIL molecules, NK1.1 expressing cells and IFN type II receptors, suggesting a role for B220+NK1.1+ dendritic cells in tumor shrinkage. Adoptive transfer of these Interferon-producing Killer Dendritic Cells (IKDC) into tumor-bearing Rag-/-IL-2Rγ-/- mice prevented tumor outgrowth whereas conventional NK cells failed to do so. IKDC can be found in Rag-/-IL-2Rγ-/- mice, they diverge from the NK cell lineage. Moreover, they exhibit a typical morphology distinguishable from classical myeloid DC or plasmacytoid DC or NK cells and are capable of antigen presentation following TLR4 and 9 triggering. We identified IKDC as pivotal sensors and effectors of the innate anti-tumor immune response (Taieb J et al Nature Medicine, in revision in back to back with D.Pardoll’s manuscript).
Abstract 14075: Thermal Insulation for Saline Irrigated Radiofrequency Ablation Electrode Allows Electrode Temperature Feedback for Lesion Formation
Authors: Hiroshi Nakagawa, Atsushi Ikeda, Fred H Wittkampf, Saurav Paul, Eric Hepler, Prathyusha Marri, Jan V Pitha, Tushar Sharma, Ralph Lazzara, Warren M Jackman
Journal: Circulation (2011)

Saline irrigation (Irg) cools electrode-tissue interface (ETI) and prevents thrombus while producing larger RF lesions. However, Irg also cools the electrode, compromising the use of electrode temp...
The Incidence and Predictors of Early- and Mid-Term Clinically Relevant Neurological Events After Transcatheter Aortic Valve Replacement in Real-World Patients
Authors: Johan Bosmans, Sabine Bleiziffer, Ulrich Gerckens, Peter Wenaweser, Stephen Brecker, Corrado Tamburino, Axel Linke
Journal: Journal of the American College of Cardiology (2015)
Updated Efficacy and Safety, and Exploratory Ki-67 Results For The MCL-001 Study Of Lenalidomide In Mantle Cell Lymphoma Patients Who Relapsed Or Were Refractory To Bortezomib
Authors: Andre Goy, Michael E. Williams, Sevgi Kalayoglu Besisik, Johannes Drach, Radhakrishnan Ramchandren, Michael J. Robertson, Irit Avivi, Jacob M Rowe, Raoul Herbrecht, Achiel Van Hoof, Miklos Egyed, Lei Zhang, Sherri Cicero, Tommy Fu, Carla Heise, Thomas E Witzig
Journal: Blood (2013)
Phase I dose-escalation study of XL147, a PI3K inhibitor administered orally to patients with solid tumors
Authors: G. Shapiro, E. Kwak, J. Baselga, J. Rodon, C. Scheffold, A. D. Laird, C. Bedell, G. Edelman
Journal: Journal of Clinical Oncology (2009)

3500 Background: XL147 is a selective inhibitor of Class I PI3K isoforms. In preclinical cancer models XL147 is cytostatic or cytoreductive as monotherapy and enhances the efficacy of targeted agents and chemotherapeutics. This open label, Phase 1 dose escalation study assesses the safety, pharmacokinetics, pharmacodynamics, and efficacy of XL147 in advanced solid tumors. Methods: For each 28 day cycle, patients (pts) receive XL147 on Days 1–21 (21/7) or as a continuous daily dose (CDD). Cycle 1 safety data determine dose-limiting toxicities (DLTs). Tumor response is assessed every 8 weeks. Results: As of December 2008, 39 pts have been treated: 36 on 21/7 across 7 dose levels (30–900 mg) and 3 on CDD at 100 mg. At 900 mg, 2 of 3 pts experienced a DLT of reversible grade 3 rash, and the MTD was established as 600 mg based on 15 pts. Drug-related toxicities included grade 3 skin rash (3 pts), grade 3 arterial thrombosis (1 pt), grade 2 transaminase elevation (1 pt), and grade 1 hyperglycemia (4 pts). XL147 exposure increased with dose from 30–400 mg and was similar from 400–900 mg. XL147 reached steady-state plasma concentrations by Day 15–20. Mean t 1/2, z at steady-state ranged from 3.7–6.3 days. Doses ≥400 mg yielded exposures that exceeded the EC 90 in xenograft models. A trend suggesting augmented food-induced changes in insulin was evident; however, glucose was minimally affected. XL147 reduced levels of phosphorylated PI3K pathway components in PBMCs, hair, skin, and tumor tissues in an exposure-dependent manner. In 2 pts dosed at the MTD, reductions of ≥70% in PI3K pathway signaling were observed in tumor tissue without compensatory upregulation of MEK/ERK phosphorylation. As of December 2008, 6 pts (3 NSCLC, 1 BCC, 1 NHL, 1 PC) continued on study &gt;6 months including 3 &gt;10 months (NHL, NSCLC, BCC). One pt with hormone refractory PC has sustained a normalization of PSA levels through 5 months. Conclusions: XL147 was generally well tolerated with the MTD for the 21/7 schedule defined as 600 mg. The most common drug-related toxicity was skin rash. Inhibition of PI3K pathway signaling has been demonstrated in tumor and surrogate tissues. Prolonged stable disease has been observed. [Table: see text]
Complexity science
Authors: I. Reid
Journal: BMJ (2002)

The development of multicellular organisms requires the well balanced and coordinated migration of many cell types. This is of particular importance within the developing nervous system, where glial cells often move long distances to reach their targets. The majority of glial cells in the peripheral nervous system of the <i>Drosophila</i> embryo is derived from the CNS and migrates along motor axons toward their targets. In the developing <i>Drosophila</i> eye, CNS-derived glial cells move outward toward the nascent photoreceptor cells, but the molecular mechanisms coupling the migration of glial cells with the growth of the eye imaginal disc are mostly unknown. Here, we used an enhancer trap approach to identify the gene <i>spinster</i>, which encodes a multipass transmembrane protein involved in endosome–lysosome trafficking, as being expressed in many glial cells. <i>spinster</i> mutants are characterized by glial overmigration. Genetic experiments demonstrate that Spinster modulates the activity of several signaling cascades. Within the migrating perineurial glial cells, Spinster is required to downregulate Dpp (Decapentaplegic) signaling activity, which ceases migratory abilities. In addition, Spinster affects the growth of the carpet cell, which indirectly modulates glial migration.
Abstract 1: Cardiac Arrest Density in a Metropolitan Area. Where to Place Automatic Defibrillators
Authors: Fredrik Folke, Gunnar H Gislason, Tina K Schramm, Pernille Buch, Steen Z Abildstrom, Lars Køber, Mette Madsen, Søren Rasmussen, Morten L Hansen, Søren L Nielsen, Freddy Lippert, Christian Torp-Pedersen
Journal: Circulation (2006)

Purpose: The aim of this study was to identify places in Copenhagen, Denmark where the cardiac arrest density was sufficiently high to merit placement of automatic defibrillators (AEDs). Hypothesis...
Defects of B-cell terminal differentiation in patients with type-1 Kabuki syndrome
Authors: Andrew W. Lindsley, Howard M. Saal, Thomas A. Burrow, Robert J. Hopkin, Oleg Shchelochkov, Pooja Khandelwal, Changchun Xie, Jack Bleesing, Lisa Filipovich, Kimberly Risma, Amal H. Assa'ad, Phillip A. Roehrs, Jonathan A. Bernstein
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 4899: Improved Blood Pressure Control and Lack of Gender Bias in a Large Veterans Affairs Population
Authors: Ross D Fletcher, Vasilios Papademetriou, Richard L Amdur, Sephen Singh, Christopher McManus, Ronald E Jones
Journal: Circulation (2009)

Introduction: Despite the proven benefits, blood pressure (BP) control rates remain low. Gender bias has emerged in several aspects of treatment of cardiovascular disease. Thus, we assessed the effect of interventions to control blood pressure in men and women in the Department of Veteran Affairs. Methods: From January of 2001 to December 2007, we assessed BP control in 460,278 men and 17,821 women patients from 15 VA hospitals in the United States. Medical interventions to control BP included use of electronic medical records with automated reminders, medical regimen adjustments, and frequent visits to both specialty and nurse run clinics. Results : Control rates (BP ≤ 140/90) over time are shown (Figure ). In Jan 2001 control rates were: 43.8% for men and 47.0% for women (p &lt; 0.001) and in June 2001 were 51.8% for men and 54.2% for women (p &lt; 0.001). After 7 years of follow up, control rates improved in both genders as follows: Jan 2007, 67.3% for men and 67.6 for women (p = NS), June 2007, 72.9% for men and 72.9% for women (p = NS, p &lt; 0.001 for seasonal differences). Overall during the follow up period while there was a 23.1% increase in control rates for men and 19.2% for women (p = 0.007), the final control rate was the same. Conclusions: High rates of BP control can be achieved in both men and women. Although early on more women than men were controlled, the control rates were identical at the end of the follow up period. No gender bias was detected for blood pressure treatment and control in this cohort. Seasonal BP variation was seen in both genders throughout the follow up period.
Cytokine Release Syndrome (CRS) after Chimeric Antigen Receptor (CAR) T Cell Therapy for Relapsed/Refractory (R/R) CLL
Authors: David L. Porter, Simon F. Lacey, Wei-Ting Hwang, Pamela Shaw, Noelle V. Frey, Anne Chew, Fang Chen, Michael Kalos, Vanessa Gonzalez, Katherine T. Marcucci, Shannon L Maude, Jan J Melenhorst, Manuel Litchman, David T. Teachey, Angela Shen, Alfonso Quintas-Cardamas, Patricia A. Wood, Bruce L. Levine, Carl H. June, Stephan A. Grupp
Journal: Blood (2014)
脓毒症：定义、流行病学和诊断
Authors: Andrew, Jain, 陶梅梅
Journal: BMJ (2008)

2005年3月29日，一名41岁的记者在做过一个小手术之后6天死于脓毒症；复活节假日周末她曾就诊于8位医生。虽然法医已经指出“乃由于对自己疾病状态的不清楚最终导致[患者死亡]”，但全国媒体关注的却是英国的非工作时间医疗服务这一政治问题。据估计，脓毒症每年的死亡率达30～50例／100000人口，位居十大死亡原因之列，各年龄段患者均可受累，通常发生在社区、长期护理机构和接受任何医学专业护理的医院人群中。
Abstract 9642: Non-Invasive Magnetic Resonance Based Three-Dimensional Voltage Maps for Electrophysiology Procedure Guidance
Authors: Takeshi Sasaki, Christopher F Miller, Rozann Hansford, Menekhem M Zviman, Charles A Henrikson, Joseph E Marine, David Spragg, Alan Cheng, Harikrishna Tandri, Sunil Sinha, Aravindan Kolandaivelu, Gordon F Tomaselli, Ronald D Berger, Hugh Calkins, David A Bluemke, Saman Nazarian
Journal: Circulation (2011)

Introduction: The association of scar on late-gadolinium enhancement cardiac magnetic resonance (LGE-CMR) with electrograms on electroanatomic map (EAM) has been investigated. We sought to quantify these associations to enable the creation of non-invasive three dimensional voltage maps (3D-VMs) based on LGE-CMR. We then tested the accuracy of the non-invasive 3D-VMs. Methods: LGE-CMR was performed in 17 patients with ischemic cardiomyopathy before ventricular tachycardia (VT) ablation. Left ventricular wall thickness (LVWT) and scar thickness (ST) were measured in each of 20 sectors per LGE-CMR short axis plane. In the first series of 13 patients (training set), EAM points were registered to the corresponding LGE-CMR images. Multivariate linear regression analysis (MLRA) was performed to determine significant independent variables and coefficients that predict local bipolar voltage. In the remaining patients (test set), non-invasive 3D-VMs were prospectively created with the regression equations by MLRA. Invasive local bipolar voltages were then compared with the estimated bipolar voltage based on non-invasive 3D-VMs. Results: A total of 1293 EAM points were analyzed. MLRA revealed independent associations between local bipolar voltage and LVWT, ST and scar location (P&lt;0.001, respectively). Prospective non-invasive 3D-VMs were then created with custom software. There was no significant difference in mean bipolar voltage on EAMs and non-invasive 3D-VMs created for the test set (1.7±1.2 vs. 1.6±1.7 mV,P=0.17). Linear regression analysis revealed a significant association between bipolar voltages on invasive EAM and noninvasive 3D-VMs (P&lt;0.001, R=0.79). Conclusions: The independent associations of local bipolar voltage with LVWT, ST on LGE-CMR enable the creation of accurate non-invasive 3D-VMs based on LGE-CMR. This novel methodology may improve the safety and efficacy of catheter ablation in patients with ischemic scar-related VT.
Autologous Stem Cell Transplant Has a Role In Consolidating Chemotherapy Given At First Disease Progression In Multiple Myeloma Treated Exclusively With Novel Agents
Authors: Bhuvan Kishore, Shankaranarayana Paneesha, Syed W Bokhari, Shrinivas Pillai, Jason Sangha, Sandeep Nagra, Emmanouil Nikolousis, Dewi Tomos Eden, Mark Crowther, Prem Mahendra, Joanne Ewing, Guy Pratt, Neil Smith, Vidhya Murthy, Clare Gardner, Richard Lovell, Kamaraj Karunanithi, Richard Christopher Chasty, Karen Yarwood, Lynn Bratby, Kathy Holder, Baker Lynda, Julie Suhr, Pip Nicolson, Mark Cook
Journal: Blood (2013)
Gaining informed consent for screening
Authors: J. Austoker
Journal: BMJ (1999)

“By offering screening to 250 000 we have helped a few, harmed thousands, disappointed many, used £1.5m each year, and kept a few lawyers in work.”1 This conclusion, by one of the authors of a report on cervical screening in Bristol, illustrates that screening, like most medical interventions, has harms as well as benefits. All the more reason therefore to ensure that patients undergoing screening are fully aware of both the benefits and the harms. Yet there are many barriers to seeking truly informed consent, and we know surprisingly little about effective ways of doing so.

The detrimental side effects of screening include anxiety, false alarms, false reassurance, unnecessary biopsies, overdiagnosis, and overtreatment. Some people have a disease detected on screening, receive treatment, yet still develop recurrent disease: we have made no real difference to their destiny, just prolonged the period they are aware of their disease. False positive results can cause major distress as well as prompting further investigations, often invasive, before the patient can be cleared. A recent study of mammography in the United Kingdom found that anxiety in women requiring further investigation because they were false positive on initial screening was still significantly higher 11 months after their recall appointment than in women who received negative results …
Abstract 11094: Cardiac Endothelial Progenitor Cells Isolated from Human Atrial Appendages Demonstrate Biological and Functional Properties Typical of Endothelial Cells
Authors: Jia Qiang He, Duc M Vu, John H Loughran, Arka Chatterjee, Ziad A Taimeh, Aruni Bhatnagar, Roberto Bolli
Journal: Circulation (2011)

Background: The number of circulating endothelial progenitor cells (EPCs) typically positive for CD34/KDR has been reported to be inversely related to cardiovascular mortality. However, it is unkno...
Medical and psychological effects of early discharge after surgery for breast cancer
Authors: B J Mander, G Cunnick, M Daultrey, G C Wishart, A D Purushotham, J. D Sheehan, J Bonnema, A M E A van Wersch, A N van Geel, J F A Pruyn, P I M Schmitz, M A Paul, T Wiggers
Journal: BMJ (1998)

Editor—Bonnema et al studied medical and psychological effects of early discharge after surgery for breast cancer.1 Their results agree with our experience of early discharge in a district general hospital in the United Kingdom.2

To compare the care received by the two groups it is necessary to know what facilities were afforded to the early discharge group. These details were lacking in the paper. We routinely provide domiciliary physiotherapy (which is important after axillary surgery) and specialist breast counselling to ensure that our patients at home receive the same treatment as those in hospital.

We are unsure why the authors chose four days as the discharge time for their early discharge group. After a pilot study we now routinely discharge all patients suitable for domiciliary care on the second postoperative morning. Ninety per cent of patients thought that this was an appropriate postoperative stay. Analysis of use of analgesia showed that patients required only oral analgesia at this time even after combined mastectomy and axillary surgery. What benefit is gained by the extra 48 hours in hospital?

The technique used by the authors to assess patient satisfaction is unusual. They recorded patients’ preference for a longer or shorter stay rather than satisfaction with the treatment they received. The 37% who recommended early discharge without having experienced it may have been reflecting dissatisfaction with their own experience rather than perceived satisfaction with a different discharge policy. We found that 90% of patients thought that our early discharge facility was excellent.

No significant difference in postoperative psychosocial variables was noted by Bonnema et al at one and four months after surgery. At one month after surgery the early discharge group will have spent about 88% of the month at home and the delayed discharge group 72%. Any effect of prolonged hospital stay will have been masked by the time the measurements were recorded. Analysis at day 9 postoperatively—the median time of leaving hospital for the delayed discharge group—would have maximised the chance of any effect of early discharge being picked up.

Early discharge after surgery for breast cancer is feasible, safe, and popular with patients. Inevitably there will be some patients for whom it is not feasible because of lack of social support or comorbidity. For most, however, it enables them to recover within the comfort of their own home and family. We would encourage others to look into ways of establishing this service.
Excess 25-hydroxyvitamin D3 exacerbates tubulointerstitial injury in mice by modulating macrophage phenotype
Authors: Yasuo Kusunoki, Isao Matsui, Takayuki Hamano, Akihiro Shimomura, Daisuke Mori, Sayoko Yonemoto, Yoshitsugu Takabatake, Yoshiharu Tsubakihara, René St-Arnaud, Yoshitaka Isaka, Hiromi Rakugi
Journal: Kidney International (2015)
Global medical knowledge database
Authors: P. Davison
Journal: BMJ (2000)

Plan represents considerable privatisationEditor-Dixon and Dewar's editorial welcomes the considerable injection of money promised in the NHS plan and claims that the plan is true to the NHS's founding principles. 1 Yet Aneurin Bevan's greatest achievement, and not one demanded of him by the Beveridge report, was the nationalisation of hospitals.He recognised that ownership was important, because with ownership comes control.The NHS plan promises 100 new hospitals by 2010 (69 of which are already in the pipeline).This will involve £7bn of new investment under the private finance initiative.Together with the new plans for some NHS operating to be carried out in the private sector, the NHS plan represents a larger privatisation than even the Tories planned.Curiously, the plan also recognises the failure of past privatisations.I remember unsuccessfully voting against the privatisation of cleaning at the London Hospital when I was a board member of the old Tower Hamlets Health Authority.Squalid wards followed, and they remain with us now.The plan recognises that this policy was a disaster.Altogether £30m of cash is to be injected into hospital trusts before the next election to pay for the consequences of this mistaken minor privatisation.How much money will we have to spend in five, 10, or 20 years' time to correct the disastrous policy of major privatisation that we are now heading for?Mr Milburn, think again, before it is too late.