tbuckley/cabot-search huggingface dataset:
Lung microbiome dynamics in COPD exacerbations
Authors: Zhang Wang, Mona Bafadhel, Koirobi Haldar, Aaron Spivak, David Mayhew, Bruce E. Miller, Ruth Tal-Singer, Sebastian L. Johnston, Mohammadali Yavari Ramsheh, Michael R. Barer, Christopher E. Brightling, James R. Brown
Journal: European Respiratory Journal (2016)

Increasing evidence suggests that the lung microbiome plays an important role in chronic obstructive pulmonary disease (COPD) severity. However, the dynamics of the lung microbiome during COPD exacerbations and its potential role in disease aetiology remain poorly understood.We completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on 476 sputum samples collected from 87 subjects with COPD at four visits defined as stable state, exacerbation, 2 weeks post-therapy and 6 weeks recovery.Our analysis revealed a dynamic lung microbiota where changes appeared to be associated with exacerbation events and indicative of specific exacerbation phenotypes. Antibiotic and steroid treatments appear to have differential effects on the lung microbiome. We depict a microbial interaction network for the lung microbiome and suggest that perturbation of a few bacterial operational taxonomic units, in particular Haemophilus spp., could greatly impact the overall microbial community structure. Furthermore, several serum and sputum biomarkers, in particular sputum interleukin-8, appear to be highly correlated with the structure and diversity of the microbiome.Our study furthers the understanding of lung microbiome dynamics in COPD patients and highlights its potential as a biomarker, and possibly a target, for future respiratory therapeutics.
Case 6-1996
Authors: R.L.H. Murphy, E.J. Merk
Journal: New England Journal of Medicine (1996)

Presentation of CaseA 40-year-old man was admitted to the hospital because of a persistent productive cough, dyspnea, and bilateral apical infiltrates.The patient had been well until two months earlier, when “tightness” developed in the chest, followed several days later by a cough productive of yellowish-to-dark-brown sputum, with increasing dyspnea.Thirty-four days before admission a small hemoptysis occurred. A beclomethasone inhaler, ofloxacin, lomefloxacin, and cefixime were prescribed in sequence, without benefit, although the cough was mildly improved with a promethazine–codeine preparation. An evaluation elsewhere showed that the hematocrit was 48.5 percent; the white-cell count was 7900 per cubic millimeter, . . .
Abstract 944: Down-regulation of CAMKK2 by androgen deprivation induces castration-resistant prostate cancer
Authors: Atsushi Mizokami, Takashi Shima, Toru Miyagi, Keiichi Kawai, Kouji Izumi, Misako Kumaki, Zhang Jian, Evan T. Keller, Mikio Namiki
Journal: Cancer Research (2012)

Abstract One of the mechanisms through which prostate cancer (PCa) relapses after androgen deprivation therapy (ADT) is to become androgen-hypersensitive and adapt to the low concentration of androgen during ADT. cDNA microarray analysis between PCa tissues before ADT and normal prostate tissues revealed that the level of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) mRNA was overexpressed 6 times in PCa more than in normal prostate. Immunohistochemical analysis of CAMKK2 protein using prostate tissue microarray showed that CAMKK2 protein was expressed well in PCa compared with normal tissue. However, the expression of CAMKK2 for the high grade PCa diminished compared with the low grade PCa. Moreover, we confirmed that the narrowness of a positive regional area of the CAMKK2 expression before ADT was a poor prognostic factor. Expression of CAMKK2 mRNA was up-regulated in the presence of DHT in LNCaP cells. Stable overexpression of CAMKK2 in LNCaP cells (LNCaP/GFP-CAMKK2), however, attenuated androgen-sensitivity. Tumorigenesis of LNCaP/GFP-CAMKK2 cells by subcutaneous injection in male SCID mice was also inhibited compared with control cells irrespective of castration. In contrast, knockdown of CAMKK2 mRNA in LNCaP cells induced androgen-hypersensitivity and stimulated LNCaP cell proliferation without DHT. Overexpression and knockdown of CAMKK2 in the presence of DHT were correlated with activation and inactivation of AMP-activated protein kinase (AMPK) that is a key kinase important for regulating cell proliferation, respectively. AMPK activation inhibited LNCaP cell proliferation. Taken together, induction of androgen-hypersensitivity after ADT may be involved in down-regulation of CAMKK2. This result may provide new therapeutic approach to keep androgen-sensitivity of PCa after ADT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 944. doi:1538-7445.AM2012-944
A6.05 Optimisation of the THP-1 cell model system for interrogation of differential macrophage polarisation in human disease
Authors: AE Graham, NA Re, E Baxter, I Carr, JR Robinson, A Aslam, A Antanaviciute, SL Mackie, AW Morgan
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Macrophages are a heterogeneous population of cells that play a central role in the pathogenesis of multiple autoimmune and inflammatory disorders. In tissues, macrophages are activated by a diverse array of signals, adopt distinct phenotypes and undertake a wide range of effector functions. Mimicking the Th cell nomenclature, a M1/M2 model of macrophage polarisation was initially proposed in murine models and has been increasingly applied to human disease. THP-1 cells are commonly used in disease model systems, however, differentiation protocols vary widely e.g. concentration and exposure times of priming agent (PMA) and polarising cytokines, necessitating the need for standardisation. M1 protocols have dominated previous literature; possibly due to the absence of clear markers and subset definition for the anti-inflammatory, M2 subtype. Our aim is to identify novel transcriptional signatures that can be used for the interrogation of human disease and ultimately the development of disease-specific <i><i>in vitro</i></i> models. <h3>Materials and methods</h3> Reported M1- and M2-specific macrophage markers were initially used as outcome measures of THP-1 polarisation experiments investigating transcriptional alterations in response to PMA concentration, rest period, cytokine stimulation times and concentrations. Publicly available RNA-seq datasets derived from human primary macrophage subtypes were used to identify additional markers. NOS and arginase production were measured to functionally confirm polarisation towards an M1 or M2 phenotype. <h3>Results</h3> Optimal conditions were selected based on the upregulation of M1 (CXCL10, IL-6 and INHBA) or M2 (CD206, CCL17 and TGM2) transcripts. A low level of PMA (5 ng/ml) and an extended rest period (72 h) were found to be sufficient to induce macrophage maturation, whilst preventing M1 polarisation bias, prior to cytokine stimulation. Characterisation of novel markers identified through analysis of public RNA-seq data is underway, along with generation of RNA-seq data from our optimised conditions. <h3>Conclusions</h3> We are developing a THP-1 cell model for generating pro- and anti-inflammatory macrophages that resemble populations found in disease states. Marker panels and transcriptional signatures will ultimately be applied to the investigation of macrophage phenotypes found <i><i>in vivo</i></i>.
PWE-041 Histopathological Uncertainties in the Management of Early Colorectal Cancers Resected through Endoscopic Therapy
Authors: J J Hurley, M Morgan, G Williams, S Dolwani
Journal: Gut (2013)

<h3>Introduction</h3> Standards for Colorectal cancer (CRC) resection specimen histology reporting consider factors thought to have apparent significance for prognosis and further therapy. Whilst well validated for surgical resection, the increasing use of advanced endoscopic resection for polyps containing previously unknown early CRC presents challenges in interpretation of these factors. In addition to tumour budding, unfavourable tumour grade, and vascular invasion, Ueno <i>et al</i>[1] proposed parameters for width and depth of submucosal invasion as risk for adverse outcome. This study aims to analyse any association between pathological factors and outcome with endoscopic resection of early CRC. <h3>Methods</h3> Retrospective review of all CRC removed endoscopically between March 2006 and March 2011. All endoscopic and surgical resection specimens were reviewed by two expert gastrointestinal histopathologists, with measurement of width and depth of submucosal invasion made. All follow up procedures, including radiology, were reviewed. <h3>Results</h3> 35 cases were identified (24 males, 11 females, median age 69 years). All patients were alive after median follow-up period of 32 months; no residual/recurrent cancers were found in any patient managed with endoscopic therapy alone. Of the 12 patients who had further surgical intervention due to reported incomplete endoscopic resection on histology, none had residual carcinoma in the subsequent resection specimen. Three patients (8.6%) were found to have Dukes C1 cancers (all T1 N1 M0). These cancers were not associated with poor differentiation or lymphovascular invasion (p = 0.546) or tumour budding of low or high intensity (p = 1.000). The relationship between the width and depth of submucosal invasion and Dukes C1 did not reach statistical significance (p = 0.096), although these three cancers did fulfil Ueno criteria. Presence of lymph node metastases was associated with Haggitt level 4 (p = 0.03), but not with the presence of tumour at the excision margin (p = 1.000) in the subsequent surgical resection group. <h3>Conclusion</h3> Our experience highlights the challenges in applying histopathological criteria to individual cases of early CRC resected via endoscopic therapy. Most patients underwent surgery for an unclear resection margin, however no residual cancer was present in the resection specimens and aside from a Haggit level 4, found no other predictors of risk lymph node metastases. Suggestions for future studies include piloting a more minimally invasive approach, such as regional lymph node dissection in selected cases as well as studying biomarkers for refining risk stratification. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Ueno H<i> et al.</i> Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 2004; 127: 385–394
Abstract LB-12: Building a novel multifaceted nano-carrier: In vivo and in vitro applications of multifunctional nanolipoprotein particles
Authors: Wei He, Sun Yi, Juntao Luo, Kit Lam, William Murphy, Matthew Coleman
Journal: Cancer Research (2012)

Abstract We have developed a novel process of production and assembly of nanolipoprotein particles (NLPs) as a multifaceted reagent for cancer imaging, drug delivery, immunomodulation and stabilizing membrane protein complexes for in vitro studies. Nanolipoproteins are components of the human HDL lipoprotein complexes that could be isolated and reconstituted to form NLPs. NLPs are discoidal nanoparticles of 10∼20 nm that self-assemble around a phospholipid bilayer. This bilayer mimics closely the cell membrane can support molecules such as dyes and proteins. NLPs present distinct advantages in terms of particle size, monodispersity and consistency: the circular protein belt constrains the dimensions of the bilayer and ensures NLP particle size distributions can be monodispersed and consistent between preparations. We have demonstrated when targeting agents and imaging agents are attached to the NLPs, they were able to accumulate at the tumor region and can be used for tumor imaging; We also managed to conjugate recombinant IL2 to NLPs. Our data showed that IL2-NLP conjugates were able to stimulate immunomodulation in mice both in vivo and in vitro. NLPs also have shown great promise for solubilizing and characterizing membrane proteins and may make many more membrane protein related complexes accessible for biophysical and biochemical study. Our approach represents a unique solution to the challenge of generating soluble and functional polytopic membrane proteins, facilitating the structural and functional characterization, providing a platform for high-throughput drug screening, and potentially a new type of carrier for tumor imaging and drug delivery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-12. doi:1538-7445.AM2012-LB-12
SP0052 Tackling the Image Issue of RMDs Through Marketing
Authors: J. Church
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Arthritis affects 1 in 5 people in Ireland, their families and friends. It is the biggest cause of workplace absenteeism in Ireland accounting for 7m lost days per annum and 30% of the €943m social welfare bill faced by the Irish government. Despite this, arthritis faces an image problem amongst the general public and many common misperceptions pervail. Arthritis is not seen as a serious illness along the lines as cancer, obesity or diseases affecting children and young adults. As a result of this image, arthritis is not seen as a serious cause worth supporting or fundraising for amongst the general population and amongst the health system in Ireland. This image or perception problem is not unique to Ireland so the hypothesis is that a solution to address this issue that works should have widespread, European and worldwide implications and value. The presentation entitled “Tackling the image issue of RMDs through Marketing” aims to take you through the process that Arthritis Ireland, the national charity and patient organisation in Ireland, adopted to tackle this image issue head on and make a positive impact on their fundraising efforts and ability therefore to fund future services. The area of arthritis is no different to any brand, product or service when it comes to creating or changing an image amongst the general public. As with all good marketing campaigns, the first step was to identify the issue creating the problem in the first place. This revealed that whilst awareness of arthritis as a condition is high, understanding of it as a serious chronic disease with very serious health and emotional impact, is very low. Secondly, a complete review of the image and perception that arthritis has was carried out and consumer insights gained into the real impact of the disease. From this review, Arthritis Ireland updatred their logo and strapline to reflect the key insight gained, that was that “Little things make a Big difference”. Its the little things that the general population take for granted that has a real impact on people with arthritis. Little things such as opening a jar in their kitchen to tying their shoe lace, take a lot longer than normal. It can often be viewed as an invisible disease and therefore compunds the lach of empathy one has for a perosn living with the disease versus other well supported or understood diseases. Arthritis Ireland, through investment in marketing tools such as TV, radio, printed materials as well as social media has commenced the long journey of changing this image in Ireland. The presentation will outline some of the marketing tools used, their impact and also draws on exaamples outside the health sector to support the approach taken. This approach to tackling an image problem also requires the right people with the right skill set and the speaker will outline that whilst this approach is making a difference, it is a long journey that can easily be transferred to other countries. <h3>Disclosure of Interest</h3> None Declared
Improved Graft Survival after Renal Transplantation in the United States, 1988 to 1996
Authors: Sundaram Hariharan, Christopher P. Johnson, Barbara A. Bresnahan, Sarah E. Taranto, Matthew J. McIntosh, Donald Stablein
Journal: New England Journal of Medicine (2000)

The introduction of cyclosporine has resulted in improvement in the short-term outcome of renal transplantation, but its effect on the long-term survival of kidney transplants is not known.
Illuminating the Potential of Pluripotent Stem Cells
Authors: Anthony Rosenzweig
Journal: New England Journal of Medicine (2010)

A classic joke often used to illustrate the nature of scientific investigation describes a drunk searching for his keys under a lamppost, even though he dropped them some distance away, because “that's where the light is.” Similarly, since the time of William Harvey, attempts to understand human cardiac physiology have relied heavily on animal models. Although much has been learned through these efforts, there are important differences among species that reinforce the intuitive premise that it would be preferable to study human pathophysiology in human cells. In this issue of the Journal, Moretti and colleagues1 elegantly show the feasibility of . . .
Abstract 5513: Treatment and mortality in men with localized prostate cancer: A population-based study in California
Authors: Weiva Sieh, Daphne Y. Lichtensztajn, David O. Nelson, Myles Cockburn, Dee W. West, James D. Brooks, Ellen T. Chang
Journal: Cancer Research (2012)

Abstract Purpose: To provide patients and physicians with population-based estimates of mortality from prostate cancer or other causes depending upon the primary treatment modality, stratified by patient age, tumor stage and grade. Patients and Methods: We conducted a 10-year competing-risk analysis of 45,440 men diagnosed with clinically localized (T1 or T2) prostate cancer in California during 1995-1998. Information on patient demographics, tumor characteristics, primary treatment and causes of death was obtained from the California Cancer Registry. Results: In this population-based observational cohort, the most common primary treatment was surgery (40.4%), followed by radiotherapy (29.1%), active surveillance (20.8%), and androgen deprivation therapy (ADT) monotherapy (9.8%). Prostate cancer mortality differed significantly (p &amp;lt; 0.0001) across treatment groups among patients &amp;lt;80 years at diagnosis with moderately or poorly differentiated disease. In these patients, the 10-year disease-specific mortality rates were generally lowest for men treated with surgery, ranging from 1.2% (95% CI, 0.8-1.7%) to 11.0% (95% CI, 8.4-14.2%); and highest for men treated with ADT monotherapy, ranging from 3.3% (95% CI, 0.8-12.5%) to 53.8% (95% CI, 34.4-72.2%). Conclusion: Use of ADT monotherapy for localized prostate cancer is not uncommon and should be reconsidered in light of the poor outcomes found in this study, lack of supportive evidence from clinical trials, and potential side effects. Although comparisons of treatment effects based on observational data are subject to confounding by indication, the cause-specific mortality estimates provided in this population-based study can help patients and physicians make management decisions based upon expected outcomes and practice patterns in the general population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5513. doi:1538-7445.AM2012-5513
Absorption and Disposition of D-Xylose in Thyrotoxicosis and Myxedema
Authors: Selwyn A. Broitman, Donald C. Bondy, Irving Yachnin, Lansing C. Hoskins, Sidney Ingbar, Norman Zamcheck
Journal: New England Journal of Medicine (1964)

A NUMBER of reports have suggested that the thyroid hormones may influence the urinary excretion of pentose. Maintenance of rats at lowered environmental temperatures or feeding of desiccated thyroid increases the output of urinary pentose1 whereas thiouracil has an opposite effect.2 Urinary excretion of endogenous ketopentose is increased in human volunteers given tri-iodothyronine.3 In thyroxine-treated rats given D-xylose by intragastric intubation the urinary excretion of pentose and ketopentose is increased although the intestinal absorption of xylose remains unchanged.4 , 5 In view of the relation between the thyroid hormones and urinary excretion of pentose, the present study of the influence of clinical . . .
Schistosoma haematobium infections acquired in Corsica, France, August 2013
Authors: M C Holtfreter, H Moné, I Müller-Stöver, G Mouahid, J Richter
Journal: Eurosurveillance (2014)

A 12 year-old boy in Germany developed urinary schistosomiasis in January 2014. He had bathed in rivers in south-eastern Corsica five months earlier. Before this case, human schistomiasis had not been reported on the island, although its vector, the snail Bulinus truncatus, locally transmitted the zoonotic Schistosoma bovis. The boy’s father excreted S. haematobium ova that were not viable; the boy’s three siblings had a positive serology against schistosomes.
P17.54 * NOVEL PROTEINS ASSOCIATED WITH INVADOPODIA STRUCTURES IN GLIOBLASTOMA MULTIFORME
Authors: D. M. Mallawaaratchy, K. L. McDonald, E. K. Sykes, M. E. Buckland, R. I. Christopherson, K. L. Kaufman
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) tumours are diffusely infiltrative making surgical resection virtually impossible. Invasion of brain parenchyma is facilitated by cell migration and degradation of the extracellular matrix (ECM). Invadopodia are actin-rich organelles that protrude from the ventral side of the plasma membrane in direct contact with the ECM and play an important role in mesenchymal cell invasion. We have characterized the ‘invasive potential’ of a panel of established GBM cell lines (n = 9) using QCM gelatin invadopodia assay (Millipore) and performed comparative, quantitative membrane mass spectrometry-based proteomic analyses of highly invasive vs. less-invasive cell lines. All GBM cells produced invadopodia, and there was a significant difference between the most invasive (U87MG) and least invasive (LN229) cells (65%, percentage of total cell area; p = 0.0001). Overall, 1667 quantifiable proteins were identified from duplicate analyses, of which 76% mapped to membrane structures using the David bioinformatics database (http://david.abcc.ncifcrf.gov). The differential abundance of 38 proteins significantly correlated with the degree of invasion (r2 > 0.45 or r2 < -0.45; n ≥ 5; p < 0.05) and are predominantly involved in cellular movement and cell-cell and interactions. Fluorescence microscopy demonstrates co-localisation of novel proteins to invadopodia structures and siRNA knockdown of a target protein confirmed its role in invadopodia-formation. Invadopodia-associated membrane proteins could be novel targets for anti-invasive GBM therapies.
Postchemotherapeutic Reversibility of Hypertrophic Osteoarthropathy in a Patient with Bronchogenic Adenocarcinoma
Authors: S Albrecht, Alain Keller
Journal: Clinical Nuclear Medicine (2003)

A 54-year-old man with bronchogenic adenocarcinoma had features of the hypertrophic osteoarthropathy syndrome. The syndrome is treated by surgical resection of the primary tumor, with rapid remission of the symptoms within 24 hours after surgery. In the case reported here, the tumor (T3N3M0) could not be resected. Clinical and scintigraphic regression of the hypertrophic osteoarthropathy was evident after chemotherapy. Bone scintigraphy is valuable when determining a patient’s response to treatment for this paraneoplastic syndrome.
QUANTITATIVE COMPARISON OF ITERATIVE RECONSTRUCTION ALGORITHMS IN ULTRA-LOW-DOSE CORONARY CT ANGIOGRAPHY
Authors: Dominik C. Benz, Tobias Fuchs, Christoph Grani, Beatrice Hirt-Moch, Fran Mikulicic, Jan Vontobel, Julia Stehli, Olivier F. Clerc, Mathias Possner, Ennio Mueller, Aju Pazhenkottil, Oliver Gaemperli, Ronny Buechel, Philipp Kaufmann
Journal: Journal of the American College of Cardiology (2016)