tbuckley/cabot-search huggingface dataset:
Soundings: St Mark’s guideline
Authors: James Owen Drife
Journal: BMJ (1999)

Dear Chaplain, It has been brought to the attention of the trust guidelines committee that you are distributing a booklet entitled The Gospel According to St Mark. The committee has obtained a copy and has requested comments from the relevant departments. Several concerns have been raised.

(1) In the title, “gospel” should be changed to “guideline.” “Gospel” implies inflexibility. With a guideline, however, adherence is closely monitored and persistent deviation results in this committee providing supportive counselling for the deviant.

(2) In chapter 3 the selection criteria for disciples are unclear. The human resources director has pointed out that no person specification was available. This is likely to generate adverse comment in relation to the lack of gender and ethnic mix. Were these posts properly advertised and were structured interviews carried out?

(3) The feeding of the five thousand (chapter 6) produced a positive response from the contract caterers, but the research director raised several questions. He advises that the subjects should have been randomised using sealed envelopes into two groups of two and a half thousand, one of which could have received five loaves and the other two fishes.

(4) In chapter 2 a patient is instructed, “Arise, and take up thy bed, and walk.” This caused considerable concern to both the physiotherapy department and the trust equipment manager. The patient should have been advised to turn on his left side and put his feet to the floor before arising. The guideline should also say, “Even if thou feelest well, thou shouldst not arise unless accompanied by a nurse or health care assistant. Thy walking will be assessed by the occupational therapist. Thy bed should be left for the next patient.” 

(5) Finally, after a computerised literature search using the keyword “gospel” the committee’s research assistant identified three other publications not referenced in your guideline. Please check if any further gospels have been published as abstracts or conference proceedings. We would ask you to combine the four published gospels (plus any unpublished ones) by formal meta-analysis.

We look forward to receiving a revised draft which can be distributed with the full authority of this committee.
Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing
Authors: Jérôme Nicod, Robert W Davies, Na Cai, Carl Hassett, Leo Goodstadt, Cormac Cosgrove, Benjamin K Yee, Vikte Lionikaite, Rebecca E McIntyre, Carol Ann Remme, Elisabeth M Lodder, Jennifer S Gregory, Tertius Hough, Russell Joynson, Hayley Phelps, Barbara Nell, Clare Rowe, Joe Wood, Alison Walling, Nasrin Bopp, Amarjit Bhomra, Polinka Hernandez-Pliego, Jacques Callebert, Richard M Aspden, Nick P Talbot, Peter A Robbins, Mark Harrison, Martin Fray, Jean-Marie Launay, Yigal M Pinto, David A Blizard, Connie R Bezzina, David J Adams, Paul Franken, Tom Weaver, Sara Wells, Steve D M Brown, Paul K Potter, Paul Klenerman, Arimantas Lionikas, Richard Mott, Jonathan Flint
Journal: Nature Genetics (2016)
In patients with MI, new-onset or existing AF increased risk for CV events at 90 days
Authors: Sean D. Pokorney, Ann Marie Navar
Journal: Annals of Internal Medicine (2016)

Source Citation Batra G, Svennblad B, Held C, et al. All types of atrial fibrillation in the setting of myocardial infarction are associated with impaired outcome. Heart. 2016. Epub ahead of print. 26928408
Vesicoureteric reflux and ureteric disorders
Authors: S. R. Payne, H. J. Testa
Journal: Clinical Nuclear Medicine (1998)

Vesicoureteral reflux (VUR) may be defined as a backward passage of urine from the bladder into the ureter and possibly the kidney. It is a non-physiological event, which may have pathological consequences for both renal parenchymal function and ureteric motility. The methods of evaluation, and treatment, of VUR are extremely variable due to a generally poor understanding of this condition [1], despite its potentially devastating effects on long-term health.
Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid–Induced AKI
Authors: Diego Martin-Sanchez, Olga Ruiz-Andres, Jonay Poveda, Susana Carrasco, Pablo Cannata-Ortiz, Maria D. Sanchez-Niño, Marta Ruiz Ortega, Jesus Egido, Andreas Linkermann, Alberto Ortiz, Ana B. Sanz
Journal: Journal of the American Society of Nephrology (2016)

AKI is histologically characterized by necrotic cell death and inflammation. Diverse pathways of regulated necrosis have been reported to contribute to AKI, but the molecular regulators involved remain unclear. We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)-induced AKI in mice. FA-AKI in mice associates with lipid peroxidation and downregulation of glutathione metabolism proteins, features that are typical of ferroptotic cell death. We show that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased histologic injury, oxidative stress, and tubular cell death in this model. With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33, an alarmin linked to necroptosis, and other chemokines and cytokines and prevented macrophage infiltration and Klotho downregulation. In contrast, the pancaspase inhibitor zVAD-fmk did not protect against FA-AKI. Additionally, although FA-AKI resulted in increased protein expression of the necroptosis mediators receptor-interacting protein kinase 3 (RIPK3) and mixed lineage domain-like protein (MLKL), targeting necroptosis with the RIPK1 inhibitor necrostatin-1 or genetic deficiency of RIPK3 or MLKL did not preserve renal function. Indeed, compared with wild-type mice, MLKL knockout mice displayed more severe AKI. However, RIPK3 knockout mice with AKI had less inflammation than their wild-type counterparts, and this effect associated with higher IL-10 concentration and regulatory T cell-to-leukocyte ratio in RIPK3 knockout mice. These data suggest that ferroptosis is the primary cause of FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necroptosis-related proteins may have additional roles in AKI.
Somatic Hypermutation and V-J Gene Usage for CLL Prognosis: Evaluating Data from Miseq NGS Vs PCR-Sanger Sequencing Approaches
Authors: Ying Huang, Kasey Hutt, Jeff Panganiban, Jeffrey Edward Miller, Jordan Thornes, Anna Gazzola, Pier Paolo Piccaluga, Michael Klass
Journal: Blood (2014)
Re: The Terminology Issue for Myeloid-Derived Suppressor Cells
Authors: Gerald Krystal, Laura Sly, Frann Antignano, Victor Ho, Jens Ruschmann, Melisa Hamilton
Journal: Cancer Research (2007)

To the Editor: 

With regard to the two recent letters ( [1][1], [2][2]) proposing a name change from myeloid suppressor cells (MSC) to myeloid-derived suppressor cells (MDSC), although we appreciate the attempt to bring clarity to the cells responsible for immunosuppression, we do not think this
Synergistic Effects of Combined Targeting of Beta-Catenin/CBP and Bcr-Abl in CML Blast Crisis Stem/Progenitor Cells in Vitro and in Vivo as Analyzed By Single Cell Mass Cytometry (CyTOF)
Authors: Hongsheng Zhou, Po Yee Mak, Hong Mu, Duncan Mak, Zhihong Zeng, Jorge Cortes, Michael Andreeff, Bing Z Carter
Journal: Blood (2015)
T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells
Authors: Imane Azzaoui, Fabrice Uhel, Delphine Rossille, Celine Pangault, Joelle Dulong, Jerome Le Priol, Thierry Lamy, Roch Houot, Steven Le Gouill, Guillaume Cartron, Pascal Godmer, Krimo Bouabdallah, Noel Milpied, Gandhi Damaj, Karin Tarte, Thierry Fest, Mikael Roussel
Journal: Blood (2016)
Pharmacodynamic Analysis Of The Inhibitory Potency Of The Tyrosine Kinase Inhibitor Midostaurin In Combination With Intensive Chemotherapy Including Allogeneic Hematopoietic Stem Cell Transplantation Followed By Maintenance Therapy In FLT3-ITD Positive Acute Myeloid Leukemia In The Ongoing AMLSG 16-10 Trial
Authors: Sabine Kayser, Mark Levis, Carina Morlok, Andrea Kuendgen, Michael Heuser, Walter Fiedler, Joerg Westermann, Katharina Goetze, Helmut R. Salih, Andreas L. Petzer, Frank Hartmann, Heinz A. Horst, Uwe M. Martens, Gerald Wulf, Michael Luebbert, Dominik Wolf, Richard Greil, Claus-Henning Koehne, Mark Ringhoffer, Hartmut Kirchner, Michael Pfreundschuh, Brigitte Schlegelberger, Patricia Erdmann, Trivikram Rajkhowa, Peter Paschka, Verena I. Gaidzik, Veronica Teleanu, Felicitas Thol, Arnold Ganser, Hartmut Doehner, Konstanze Doehner, Richard F. Schlenk
Journal: Blood (2013)
Simple, Sensitive and Accurate Multiplex Detection of Clinically Important Melanoma DNA Mutations in Circulating Tumour DNA with SERS Nanotags
Authors: Eugene J.H. Wee, Yuling Wang, Simon Chang-Hao Tsao, Matt Trau
Journal: Theranostics (2016)

Sensitive and accurate identification of specific DNA mutations can influence clinical decisions.However accurate diagnosis from limiting samples such as circulating tumour DNA (ctDNA) is challenging.Current approaches based on fluorescence such as quantitative PCR (qPCR) and more recently, droplet digital PCR (ddPCR) have limitations in multiplex detection, sensitivity and the need for expensive specialized equipment.Herein we describe an assay capitalizing on the multiplexing and sensitivity benefits of surface-enhanced Raman spectroscopy (SERS) with the simplicity of standard PCR to address the limitations of current approaches.This proof-of-concept method could reproducibly detect as few as 0.1% (10 copies, CV < 9%) of target sequences thus demonstrating the high sensitivity of the method.The method was then applied to specifically detect three important melanoma mutations in multiplex.Finally, the PCR/SERS assay was used to genotype cell lines and ctDNA from serum samples where results subsequently validated with ddPCR.With ddPCR-like sensitivity and accuracy yet at the convenience of standard PCR, we believe this multiplex PCR/SERS method could find wide applications in both diagnostics and research.
Prenatal Arsenic Exposure and Birth Outcomes among a Population Residing near a Mining-Related Superfund Site
Authors: Birgit Claus Henn, Adrienne S. Ettinger, Marianne R. Hopkins, Rebecca Jim, Chitra Amarasiriwardena, David C. Christiani, Brent A. Coull, David C. Bellinger, Robert O. Wright
Journal: Environmental Health Perspectives (2016)

Background:Limited epidemiologic data exist on prenatal arsenic exposure and fetal growth, particularly in the context of co-exposure to other toxic metals.Objective:We examined whether prenatal arsenic exposure predicts birth outcomes among a rural U.S. population, while adjusting for exposure to lead and manganese.Methods:We collected maternal and umbilical cord blood samples at delivery from 622 mother–infant pairs residing near a mining-related Superfund site in Northeast Oklahoma. Whole blood arsenic, lead, and manganese were measured using inductively coupled plasma mass spectrometry. We modeled associations between arsenic concentrations and birth weight, gestational age, head circumference, and birth weight for gestational age.Results:Median (25th–75th percentile) maternal and umbilical cord blood metal concentrations, respectively, were as follows: arsenic, 1.4 (1.0–2.3) and 2.4 (1.8–3.3) μg/L; lead, 0.6 (0.4–0.9) and 0.4 (0.3–0.6) μg/dL; manganese, 22.7 (18.8–29.3) and 41.7 (32.2–50.4) μg/L. We estimated negative associations between maternal blood arsenic concentrations and birth outcomes. In multivariable regression models adjusted for lead and manganese, an interquartile range increase in maternal blood arsenic was associated with –77.5 g (95% CI: –127.8, –27.3) birth weight, –0.13 weeks (95% CI: –0.27, 0.01) gestation, –0.22 cm (95% CI: –0.42, –0.03) head circumference, and –0.14 (95% CI: –0.24, –0.04) birth weight for gestational age z-score units. Interactions between arsenic concentrations and lead or manganese were not statistically significant.Conclusions:In a population with environmental exposure levels similar to the U.S. general population, maternal blood arsenic was negatively associated with fetal growth. Given the potential for relatively common fetal and early childhood arsenic exposures, our finding that prenatal arsenic can adversely affect birth outcomes is of considerable public health importance.Citation:Claus Henn B, Ettinger AS, Hopkins MR, Jim R, Amarasiriwardena C, Christiani DC, Coull BA, Bellinger DC, Wright RO. 2016. Prenatal arsenic exposure and birth outcomes among a population residing near a mining-related Superfund site. Environ Health Perspect 124:1308–1315; http://dx.doi.org/10.1289/ehp.1510070
Phase II evaluation of 90yttrium resin microspheres (sir-spheres) monotherapy in unresectable, heavily pre-treated colorectal liver metastaseses
Authors: M Cosimelli, R Mancini, L Carapanese, R Sciuto, G Pizzi, I Sperduti, R Golfieri, E Giampaima, F Izzo, F Fiore, P Cagol, S Bacchetti, C Maini
Journal: Annals of Oncology (2008)
P199 Does Average Volume Assured Pressure Support (AVAPS) ventilation improve safety in Motor Neurone Disease?: Abstract P199 Table 1
Authors: TS Buttle, S Nathoo, J Kindred, S Banerjee
Journal: Thorax (2015)

<h3></h3> Average volume-assured pressure support (AVAPS) is a novel way to deliver NIV. In this mode, a target tidal volume is set, and the device adjusts the pressure support to reach that volume. A particular potential benefit is that it may adapt to disease progression, as in patients with progressive Motor Neurone Disease. NICE guidance (2010) recommend follow up every 3 months. We propose to investigate if this new technology improves safety during the initial period of ventilator support. <h3>Aim</h3> To identify the trend in pressure support and hours of use of AVAPS ventilation in patients with ventilatory failure due to MND. Look at compliance and tolerability on patients with AVAPS. <h3>Methods</h3> Retrospective review of case notes and downloads from the ventilators of 6 patients identified to have started on AVAPS due to ventilatory failure secondary to MND. Average AHI, IPAP, EPAP, hours of use, compliance during first three months were reviewed. <h3>Results</h3> There was no significant change in IPAP (Mean 14.78 at 1 month, 14.98 at 3 months) or EPAP (5.91 at 1 month, 6.57 at 3 months). Average use (6 hrs 44 min at one month rising to 8 hrs 48 min at three months) and compliance (percent greater than 4 h 77.6% at 1 month to 89.5% at 3 months) did show positive trends but did not reach significance. <h3>Conclusions</h3> This study shows an increase in average hours of use and compliance in the first 3 months of use. Tidal volumes and pressure support remain preserved. This initial data would suggest no benefit in providing the more expensive AVAPS machine compared to standard BiPAP S/T mode. Larger prospective studies looking at disease progression and ventilation usage in MND are warranted.
Cost-effectiveness of cetuximab for the first-line treatment of squamous cell carcinoma of the head and neck (SCCHN) in Canada
Authors: J. Sambrook, A. R. Levy, K. M. Johnston, N. J. Ricard, C. Bourgault, B. M. Donato, F. G. Sheehan, S. J. Hotte, M. R. Chasen, A. H. Briggs
Journal: Journal of Clinical Oncology (2009)

e17000 Background: Squamous cell carcinoma of the head and neck (SCCHN) is a disfiguring and potentially fatal condition. Cetuximab is a new therapeutic option which has been shown to improve locoregional control (LRC) and reduce mortality in the treatment of locally and regionally advanced disease. Objectives: To estimate the incremental cost-utility of cetuximab plus radiotherapy (CxRT) versus cisplatin plus radiotherapy (CsRT) among platinum eligible patients and versus RT alone in platinum ineligible patients in Canada. Methods: A lifetime transition model was developed with four health states: 1) acute treatment phase; 2) LRC; 3) disease progression and 4) death. Adverse events were accounted for in the first two states. Efficacy of treatment (LRC and overall survival) was obtained from the literature. Based on network meta-analyses, CsRT and CxRT were assumed to have equal efficacy. Resource use was obtained from published literature and clinical expert opinion. The perspective adopted was that of a provincial ministry of health or cancer agency. Utilities were obtained from a previous study of United Kingdom oncology nurses. Costs (2008 CDN$) and outcomes were discounted at 5% annually. Incremental cost-effectiveness ratios (ICERs) were reported with one-way and probabilistic sensitivity analyses performed to assess robustness of results. A priori sub-group analyses were carried out by baseline Karnofsky Performance Scores (KPS). Results: Among all patients (KPS 60–100), the ICERs comparing CxRT to RT were $19,740/QALY (95% CI: $11,122 to $695,295) among platinum ineligible patients and for CxRT vs. CsRT, $99,147/QALY (95% CI: $75,998 to $148,951) among platinum eligible patients. ICERs decreased with increasing KPS scores. At a willingness to pay of $50,000 among platinum-ineligible patients and $100,000 among platinum-eligible patients, the likelihood that CxRT is cost-effective is 90% and 45% respectively. Sensitivity analyses indicated that time horizon and assumptions about CsRT effectiveness had the largest impact on results. Conclusion: Cetuximab is an economically attractive option for SCCHN patients. [Table: see text]
Ligation-free ribosome profiling of cell type-specific translation in the brain
Authors: Nicholas Hornstein, Daniela Torres, Sohani Das Sharma, Guomei Tang, Peter Canoll, Peter A. Sims
Journal: Genome biology (2016)

Ribosome profiling has emerged as a powerful tool for genome-wide measurements of translation, but library construction requires multiple ligation steps and remains cumbersome relative to more conventional deep-sequencing experiments. We report a new, ligation-free approach to ribosome profiling that does not require ligation. Library construction for ligation-free ribosome profiling can be completed in one day with as little as 1 ng of purified RNA footprints. We apply ligation-free ribosome profiling to mouse brain tissue to identify new patterns of cell type-specific translation and test its ability to identify translational targets of mTOR signaling in the brain.
Comparison of the safety and immunogenicity of live attenuated and inactivated hepatitis A vaccine in healthy Chinese children aged 18 months to 16 years: results from a randomized, parallel controlled, phase IV study
Authors: F. Ma, J. Yang, G. Kang, Q. Sun, P. Lu, Y. Zhao, Z. Wang, J. Luo, Z. Wang
Journal: Clinical Microbiology and Infection (2016)

For large-scale immunization of children with hepatitis A (HA) vaccines in China, accurately designed studies comparing the safety and immunogenicity of the live attenuated HA vaccine (HA-L) and inactivated HA vaccine (HA-I) are necessary. A randomized, parallel controlled, phase IV clinical trial was conducted with 6000 healthy children aged 18 months to 16 years. HA-L or HA-I was administered at a ratio of 1: 1 to randomized selected participants. The safety and immunogenicity were evaluated. Both HA-L and HA-I were well tolerated by all participants. The immunogenicity results showed that the seroconversion rates (HA-L versus HA-I: 98.0% versus 100%, respectively, p >0.05), and geometric mean concentrations in participants negative for antibodies against HA virus IgG (anti-HAV IgG) before vaccination did not differ significantly between the two types of vaccines (HA-L versus HA-I first dose: 898.9 versus 886.2 mIU/mL, respectively, p >0.05). After administration of the booster dose of HA-I, the geometric mean concentrations of anti-HAV IgG (HA-I booster dose: 2591.2 mIU/mL) was higher than that after the first dose (p <0.05) and that reported in participants administered HA-L (p <0.05). Additionally, 12 (25%) of the 48 randomized selected participants who received HA-L tested positive for HA antigen in stool samples. Hence, both HA-L and HA-I could provide acceptable immunogenicity in children. The effects of long-term immunogenicity after natural exposure to wild-type HA virus and the possibility of mutational shifts of the live vaccine virus in the field need to be studied in more detail.
Intravenous iron therapy in non‐anemic iron‐deficient menstruating adolescent females with fatigue
Authors: Ruchika Sharma, Joseph R. Stanek, Terah L. Koch, Linda Grooms, Sarah H. O'Brien
Journal: American Journal of Hematology (2016)

Menstruating women, with or without underlying bleeding disorders, are at increased risk for developing iron deficiency-related fatigue, even in the absence of anemia. Oral iron therapy has limitations which include poor absorption and non-adherence due to gastrointestinal side effects. We performed a prospective clinical trial of post-menarchal adolescent females with iron-deficiency with or without mild anemia and fatigue who received a standardized regimen of intravenous iron sucrose. The baseline mean (SD) hemoglobin was 11.96 g dl(-1) (1.05) in 20 girls (ages 14-21 years); with a range of 10.3-14.1 g dl(-1) . In this cohort, intravenous iron was well tolerated and patients demonstrated a sustained increase in ferritin levels with means (SD) of 13.4 ng ml(-1) (13.1) at baseline to 141.5 ng ml(-1) (104.5) at 6 weeks and 85.2 ng ml(-1) (128.4) at 6 months after the infusions. We used a standardized (Peds QL(TM) Multidimensional) fatigue scale to objectively measure fatigue and proxy scores by parents with mean screening scores (SD) of 35.2 (16.8) and 31.9 (19.6), respectively. We demonstrated a clinically significant improvement both in patient as well as parent fatigue scores (in 19 out of 20 subjects) at 6 weeks (Mean (SD) 58.3 (21.3) [P < 0.0001] and 57 (24.4) [P < 0.0001], respectively); as well as 3 and 6 months after the iron infusions. In nonanemic patients, iron administration did not significantly influence hemoglobin concentration. Therefore, the fatigue-reducing effects of iron therapy reflect the nonhematological functions of iron. Am. J. Hematol. 91:973-977, 2016. © 2016 Wiley Periodicals, Inc.