tbuckley/cabot-search huggingface dataset:
PTU-063 High reticulocyte count predicts mortality in patients awaiting liver transplantation
Authors: R Parker, M A Armstrong, C Corbett, I Rowe, B Stephenson, D Houlihan, J Ferguson
Journal: Gut (2012)

<h3>Introduction</h3> The shortage of donor organs for liver transplantation (LT) makes it essential that organs are allocated to patients with greatest need. There has been increasing interest in haemoglobin as a predictor of LT outcomes. We investigated red cell parameters as predictors of survival after LT assessment. <h3>Methods</h3> Data on patients with end-stage liver disease assessed for LT between 2008 and 2010 at University Hospitals Birmingham, UK, were reviewed retrospectively. Kaplan–Meier and Cox regression analysis identified parameters predictive of death on the waiting list. To construct an updated UKELD model including high reticulocyte count (defined as &gt;80), cases that had not received LT at 12 months were randomly divided into two groups (2:1 ratio) to for model building and testing. Accuracy of the existing and new and models was tested by calculation of c-statistics. <h3>Results</h3> Data were collected from 393 patients. Median age was 55 years (range 17–73), 60% were male. Median UKELD was 56 (44–76). Median follow-up was 18 (0–45) months. In total 144 (37%) underwent LT. Abnormal reticulocyte count, seen in 120 patients (31%), was greatest predictor of death without LT (HR 3.1; 95% CI 1.7 to 5.6), compared to haemoglobin (HR 2.5; 95% CI 1.3 to 4.5) and MCV (HR 0.6; 95% CI 0.3 to 1.2). Abnormal reticulocyte count remained a significant predictor of death after adjustment for age, gender and diagnosis (p80; yes=1, No=0]). This model had improved predictive accuracy with a c-statistic of 0.79. <h3>Conclusion</h3> High reticulocyte count is associated with increased risk of death in patients awaiting LT. Remodelling UKELD to include high reticulocyte count improved accuracy of predicting death on the LT waiting list. <h3>Competing interests</h3> None declared.
Serious laryngeal edema during endoscopic resection for squamous cell carcinoma of the esophagus
Authors: N. Ara, K. Uno, K. Iijima, T. Koike, N. Asano, T. Shimosegawa
Journal: Endoscopy (2013)

The detection of early esophageal squamous cell carcinoma (ESCC) in patients following radiotherapy for squamous cell carcinoma of the head and neck (HNSCC) has increased with the development of endoscopic technologies. The aim of the current case - control study was to elucidate the risk factors of serious laryngeal edema, a lethal complication that occurs during endoscopic resection for ESCC. Among 184 consecutive patients who were treated by endoscopic resection for ESCC between January 2009 and May 2012, five of 22 patients with a history of radiotherapy for HNSCC suffered from serious laryngeal edema, which was not observed in patients who had not undergone radiotherapy. The susceptibility to serious laryngeal edema in patients with a history of radiotherapy followed by neck dissection for HNSCC was significantly greater than those without such histories. Despite the limited number of cases, we suggest that previous radiotherapy followed by neck dissection for HNSCC might be a predictive factor for serious laryngeal edema during endoscopic resection.
Ready…aim…fire into the lumen
Authors: David A. Shifrin, Jr, Matthew J. Tyska
Journal: Gut Microbes (2012)

Recent studies from our laboratory revealed that enterocyte brush border microvilli release small vesicles laden with host defense machinery into the intestinal lumen. In this addendum, we introduce a multi-faceted model for the function of these lumenal vesicles in the gut; we also consider some of the important unanswered questions that must be addressed in order to develop our understanding of this novel aspect of innate intestinal immunity.
Abstract SY07-03: The ubiquitin-based response to DNA double-strand breaks
Authors: Daniel Durocher
Journal: Cancer Research (2012)

Abstract The chromatin-based response to DNA double-strand breaks (DSBs) is characterized by the accumulation of DNA repair factors and DNA damage signaling molecules within a large domain that surrounds the lesion. This response is largely dependent on ATM-dependent phosphorylation but also on chromatin ubiquitylation. Indeed, the RNF8 and RNF168 E3 ubiquitin ligases are necessary for the accumulation of proteins such as 53BP1, BRCA1 and RAD18 at sites of DNA damage. The critical importance of this pathway is manifested by the observation that biallelic mutations in the RNF168 gene results in an ataxia-telangiectasia-like syndrome referred to as RIDDLE. We are interested in understanding how this pathway is regulated and how ubiquitin-dependent protein interactions orchestrate the hierarchy of protein recruitment at sites of DNA lesions. I will present our current understanding on the regulation and organization of this signaling cascade and I will contend that DNA double-strand break signaling will be a useful system for deciphering the contribution of non-degradative ubiquitylation in cell signaling. 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 SY07-03. doi:1538-7445.AM2012-SY07-03
Reply to Rostami et al.
Authors: R. Singh, W. Tam, G. Nind, B. George, M. Shetti, G. Tucker
Journal: Endoscopy (2011)

We thank Rostami et al. for their interest in our paper [1]. In this feasibility study, narrow band imaging with optical magnification (NBI-Z) was clearly able to discern the villous morphology in keeping with the Marsh 3 classification.
Salient Features of Endonuclease Platforms for Therapeutic Genome Editing
Authors: Michael T Certo, Richard A Morgan
Journal: Molecular Therapy (2016)

Emerging gene-editing technologies are nearing a revolutionary phase in genetic medicine: precisely modifying or repairing causal genetic defects. This may include any number of DNA sequence manipulations, such as knocking out a deleterious gene, introducing a particular mutation, or directly repairing a defective sequence by site-specific recombination. All of these edits can currently be achieved via programmable rare-cutting endonucleases to create targeted DNA breaks that can engage and exploit endogenous DNA repair pathways to impart site-specific genetic changes. Over the past decade, several distinct technologies for introducing site-specific DNA breaks have been developed, yet the different biological origins of these gene-editing technologies bring along inherent differences in parameters that impact clinical implementation. This review aims to provide an accessible overview of the various endonuclease-based gene-editing platforms, highlighting the strengths and weakness of each with respect to therapeutic applications.
Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses
Authors: Gail M. Gauvreau, Jonathan P. Arm, Louis-Philippe Boulet, Richard Leigh, Donald W. Cockcroft, Beth E. Davis, Irvin Mayers, J. Mark FitzGerald, Barbro Dahlen, Kieran J. Killian, Michel Laviolette, Christopher Carlsten, Nikolaos Lazarinis, Richard M. Watson, Joanne Milot, Veronica Swystun, Miranda Bowen, Linda Hui, Ann-Sofie Lantz, Karin Meiser, Suzanne Maahs, Philip J. Lowe, Andrej Skerjanec, Anton Drollmann, Paul M. O'Byrne
Journal: Journal of Allergy and Clinical Immunology (2016)
Can high resolution microendoscopy improve the resect and discard strategy?
Authors: C. Hassan, J. East
Journal: Endoscopy (2013)

Polypectomy is a major determinant of the cost of colonoscopy screening [1]. This appears to be related to the high prevalence of polyps in the general population. It has recently been estimated that up to 42 % of screenees will present with at least one polyp at screening colonoscopy [2]. This rate is likely to increase with the widespread implementation of high definition endoscopy and of quality assurance programs for screening colonoscopy [3]. Polypectomy costs are partly related to the cost of pathological examination. With regard to diminutive polyps (≤ 5 mm in diameter), which represent more than 60 % of all polyps detected by colonoscopy during average-risk screening [2], the additional cost of post-polypectomy pathological examination is mainly justified by the need to differentiate between precancerous adenomatous and hyperplastic polyps. To reduce such costs, a policy of discarding the polyp and avoiding the expense of pathological examination has been proposed; this has been termed the resect and discard policy [4] [5] [6]. Its main assumption is that if endoscopy were to allow in vivo prediction of the histology of the polyp, the additional value of pathological examination could become marginal, such examination then being inefficient and/or cost-ineffective [1] [7] [8].
WHO leader to step down
Authors: R. Walgate
Journal: BMJ (1997)

Dr Hiroshi Nakajima, the controversial director general of the World Health Organisation, has announced that he will not seek a third five year term, leaving the way open for a new broom at the organisation from June 1998.



Dr Nakajimi has been criticised for weak leadership.

WHO



Dr Nakajima, who is 69, has frequently been criticised by the United States and other Western countries for poor management and weak leadership since he took over the helm in 1988 (5 April, p 998). He is believed to have been discussing his position with the Japanese government-which backed him strongly for the …
797 HIGH PREVALENCE OF CHRONIC HEPATITIS C IN 8009 PATIENTS WITH MIGRATION BACKGROUND LIVING IN GERMANY
Authors: P. Buggisch, J. Petersen, I. Urlea-Schön, S. Rossol, B. Möller, R. Heyne, J. Weissmann, M. Malek, G. Teuber, C. John, K.-H. Hey, L. Melcher, T. Witth öft, H. Blaak, D. Hartmann, M. Bilzer
Journal: Journal of Hepatology (2013)
IT-20 * OVEREXPRESSION OF IL13Ra2: ASSESSMENT OF PRO-AGGRESSIVE AND PRO-INVASIVE PHENOTYPES OF MALIGNANT GLIOMA IN A SYNGENEIC ANIMAL MODEL
Authors: A. Mangraviti, S. Sengupta, I. Paldor, D. Rowshanshad, P. Sampath, A. Olivi, B. Tyler, H. Brem
Journal: Neuro-Oncology (2014)

BACKGROUND: IL13Rα2 is a promising target for novel therapies in glioblastoma (GBM) due to its overexpression in tumor cells as well as glioma-initiating cells, which are responsible for the growth and recurrence of GBM. The role of IL13Ra2, found heterogeneously expressed in GBMs, is not fully understood and better targeting strategies are necessary for its clinical application. This study investigated the effectiveness of different patterns of IL13Rα2 expression on the survival of syngeneic rodent glioma models. This study also aims to act as a blueprint for further tests of the level of immune response to the target immunotherapy in immunocompetent mice bearing GBMs with different levels of IL13Rα2 expression. METHODS: G26 murine glioma cell line, with transfected to express hIL13Rα2 (G26-H2) and vector control (G26-V2) were intracranially injected in two groups of C57Bl/6 mice respectively. The metric analyzed for outcome was survival. Histological analysis were used to evaluate the level of IL13Ra2 expression in primary tissue obtained from patients with high gliomas. RESULTS: Two populations of G26 glioma cell lines were established per hIL13Rα2 expression: the hIL13Rα2+ and the hIL13Rα2−. In vivo, the cell lines showed a significant difference in survival: the group that received intracranial injection of G26-H2 cells (100% positive for hIL13Rα2) had a median survival of 29.5 days compared to 49 days for group receiving G26-V2 cells (100% negative for h IL13Rα2), p <0.0172. CONCLUSION: We assessed two different populations of G26 glioma cell lines: h IL13Rα2+ and h IL13Rα2−. In vivo, after intracranial implantation, the two populations showed a significant difference in survival. These results confirm the role of hIL13Rα2 overexpression in specific subtypes of GBMs, and most likely the most aggressive ones.
SP0195 Sugars on ACPA: What Can They Do?
Authors: H. U. Scherer
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Autoantibodies are considered to be major players in the pathogenesis of various autoimmune diseases. Although the antigenic target is usually known, both the mechanism by which autoantibodies are generated and the mechanism by which they contribute to disease pathogenesis are frequently unknown. Moreover, autoimmune diseases are different from infectious diseases because of the continuous presence of the antigen that can cause persistent stimulation of the autoreactive immune response. In rheumatoid arthritis, autoantibodies to citrullinated antigens are considered to be involved in disease pathogenesis, although also here, the underlying mechanisms are incompletely understood. Antibodies are glycoproteins, with glycans attached to both the Fc part and the Fab portion. These glycans modulate the way by which antibodies interact with both the respective autoantigen and specific receptors on the surface of immune cells. In fact, variations in glycan structures can determine whether an antibody initiates or inhibits inflammatory responses. Based on these considerations, we have studied the glycosylation of IgG anti-citrullinated protein antibodies (IgG-ACPA) in detail and observed specific glycosylation patterns in both the Fc part and the Fab portion. In part, these glycosylation patterns are acquired shortly before disease onset. These studies give insight into potential interactions between IgG-ACPA and Fcγ-receptors as well as cell surface lectins. The presentation will cover the above mentioned aspects and provide data on ACPA-specific glycosylation patterns. <h3>Disclosure of Interest</h3> None Declared
TM-601 targets human cancer cells via a phosphatidylinositol phosphate in lamellipodia
Authors: C. A. Grimes, M. A. Gonda, V. L. Alvarez
Journal: Journal of Clinical Oncology (2005)

9556 Background: Tumor formation requires altered motility of transforming cells to invade surrounding tissues. This altered cellular motility involves formation of lamellipodia, protrusions of the plasma membrane at the leading edge of the cell. Recent studies establish a role for phosphatidylinositol-3-kinase (PI3K) and the PI3K/Akt pathway in initiation of membrane ruffling and actin stress fiber formation, events necessary for lamellipodia formation. PI3K regulates the membrane phospholipids PI(4,5)P2 and PI(3,4,5)P3 that serve pivotal roles in cell signaling, and when deregulated, contribute to tumor formation. Methods: We investigated the mechanism of action of TM-601, a synthetic peptide derivative of scorpion venom, in human cancer cells. Multiple established human cancer cell lines were used in these studies, including solid tumor (glioblastoma, prostate, breast, lung, melanoma, colon) and hematologic tumor cell lines (lymphoma, leukemia, myeloma). Histochemical staining, FACS analysis, and in vitro binding assays were used to characterize TM-601 binding, identify specific intracellular targets, and investigate downstream effects. Results: TM-601 bound all cancer cell lines tested and histological staining localized binding to the lamellipodia of cancer cells. Using in vitro binding assays, we identified phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), as the cellular target of TM-601. Additionally, our results indicated multiple downstream consequences of TM-601 binding to PI(4,5)P2, including reduced activity of PI3Kγ, increased activity of GSK3β, and inhibition of DNA synthesis. Conclusions: TM-601 is a novel 36 amino-acid peptide that targets human cancer cells via a phosphatidylinositol phosphate resulting in altered activity of the PI3K/Akt signal transduction pathway. 131I-TM-601 is currently in Phase II clinical development for the treatment of adult recurrent glioma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration TransMolecular
PTH-060 Evaluation Of An Established Community Gastroenterology Clinic With Comparison To Secondary Care
Authors: OF Ahmad, R Dawood, C Oesterling, D Rusk, A Akbar
Journal: Gut (2014)

<h3>Introduction</h3> Community based specialist clinics improve patient experience and access to healthcare whilst improving GP-Specialist communication.<sup>1</sup> Commissioning dictates that future management of chronic gastro-intestinal conditions needs to involve integrated care. We reviewed the outcomes of an established gastroenterology community clinic run for 3 years by two General Practitioners with a specialist interest in gastroenterology (GPwSIs) and a consultant gastroenterologist from the local hospital. <h3>Methods</h3> A weekly gastroenterology community clinic in primary care was established to service 35 local General Practices. Data was collected from January-September 2013 using referral letters and an electronic database and compared to the local hospital general gastroenterology clinics. <h3>Results</h3> Of 490 patients referred 284 (58%) were triaged to community, 188 (38%) referred onwards to secondary care and 18 (4%) were returned to the referring GP. 37% of appointments were conducted by the consultant. The proportion of patients that did not attend was lower in the community (10%) than secondary care (22%). 86% were discharged back to their referring GP; 16% after the 1<sup>st</sup> appointment and 84% after one further follow up appointment. Others were directly referred to relevant secondary care. 80% had further investigations (39% Gastroscopy, 24% Colonoscopy, 22% CT scan, 12% Ultrasound abdomen, 9% flexible sigmoidoscopy, 1% Oesophageal manometry) all performed in the local hospital. Median wait time from referral to 1<sup>st</sup> clinic appointment was 28 days in the community (56 days in the local hospital). Intra-clinic wait time in community was an average of 3 min (38 min in secondary care). A community patient satisfaction survey (N=102) revealed that 88% would definitely recommend the clinic to a friend, with high levels of satisfaction. A secondary care satisfaction survey (N=214) showed that although overall satisfaction was similar, there was relative dissatisfaction of waiting times, waiting area and communication. <h3>Conclusion</h3> This novel gastroenterology community clinic delivers high quality care closer to patients. It is associated with shorter refe, UKrral waiting times, high discharge rates and excellent patient satisfaction scores. Additional benefits include enhancement of primary/secondary care links, mentoring and teaching of GPwSIs, continuity of care and direct access to onward referral to secondary care for further management across specialties. Further follow up is necessary to evaluate the effect on local healthcare delivery. <h3>Reference</h3> 1 Powell J. Systematic review of outreach clinics in primary care in the UK. <i>J Health Serv Res Policy</i> 2002:7:177–83 <h3>Disclosure of Interest</h3> None Declared.
Endoscopic ultrasound and fine needle aspiration for the diagnosis of extragonadal seminoma metastatic to the pancreas
Authors: Mario Tadic, Tajana Stoos-Veic
Journal: Endoscopy (2014)

A 35-year man presented with back pain and paraparesis. Computed tomography of the abdomen and chest showed a pancreatic mass and a spinal canal lesion from L5 to S3. Of note, a year earlier, he had been in a motor vehicle accident, at which time emergency computed tomography of the chest showed a mediastinal tumor. Tissue obtained during thoracoscopy demonstrated a granulomatous tissue reaction.
Abstract 327: Genomic profiling of sentinel lymph node breast cancer metastasis
Authors: Clarissa Torresan, Savana C. Santos, Jordi Camps, Silma F. Pereira, Enilze M. Ribeiro, Iglenir J. Cavalli, Bassem R. Haddad, Luciane R. Cavalli
Journal: Cancer Research (2010)

Abstract The sentinel lymph node (SLN) is the first node in the axilla to harbor malignant cells in breast tumors with metastasis, and its positivity is an indication for axillary lymph node dissection. Despite significant improvement in the methods for detection of tumor cells at this site, there are a still significant number of false negative cases and the inability to detect malignant cells in lower abundance, such as in the case of micrometastasis. We propose to use methods based on the genomic alterations, which present higher sensitivity and accuracy, and can be used to augment the current methods to identify the epithelial malignant cells at the SLN. In this study, we performed CGH and array-CGH analysis in microdissected tumors cells from the SLN metastatic lesions to identify DNA copy number changes. We compared the changes observed in the SLN lesion to the ones present in the corresponding primary tumors (PT) from the same patients. Here we present the results from the initial analysis of 10 FFPE (formalin-fixed paraffin-embedded) breast cancer samples (5 pairs of SLN and PT). DNA copy number changes were detected by both methods in all the cases analyzed. A remarkable similarity in the DNA profiles between the SLN metastatic lesions and the corresponding PT were observed, despite the high level of heterogeneity observed among the cases. CGH analysis revealed most frequently gains of chromosomal regions (at both lesions) involving 1p, 1q, 6q, 9q, 11p, 11q, 13q, 16p, 17q, 19p, 19q and Xq. Array-CGH analysis detected both amplifications and deletions, affecting mostly the chromosome regions 1p (genes affected KLHL17, NOC2L, PPIAL4), 9q (ANKRD20A, COL5A), 11p (PSMD13, SIRT3), 15q (MAN2C1), 19p (MUC16, AZU1) and 20q regions (PSMA7). In addition, several genes of the HIST, FLJ, SLC and TRIM family as well as the homeobox families HOX and NK were involved in the alterations. FISH analysis is being conducted to confirm the array-CGH findings as well as the analysis of additional matching samples. The assessment of copy number changes in the SLN metastasis (and in its correspondent PT) using genomic profiling is a very sensitive method and will lead to the identification of genomic alterations that can reliably characterize breast tumor cells at the SLN lesions. Once these alterations are validated in larger series of patients, they can be used as molecular markers that can improve the predictive value of the current established methods of SLN evaluation in the identification of patients at higher risk of developing axillary lymph node metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 327.