tbuckley/cabot-search huggingface dataset:
Abstract 1946: Identification of miRNAs that contribute to melanoma brain metastasis
Authors: Avital Gaziel, Silvia Menendez, Miguel F. Segura, Jan Zakrzewski, Amy Rose, Robert S. Kerbel, Farbod Darvishian, Dalia Cohen, Iman Osman, Eva Hernando
Journal: Cancer Research (2010)

Abstract Brain metastasis occurs in a large proportion of metastatic melanoma patients and is associated with a dismal prognosis. However, the molecular mechanisms that govern melanoma tropism to the brain remain poorly understood. MicroRNAs (miRNAs) play essential roles in many physiological and pathological processes, and have been recently shown to exert key roles during cancer metastasis. In this study we find that specific miRNAs may be important mediators of melanoma dissemination to the brain. First, we conducted a miRNA microarray analysis of metastatic melanoma tissues that revealed a subset of miRNAs differentially expressed in brain metastases (n=11) relative to other sites (n=48). A brain-specific signature comprised of seven miRNAs was further validated in an independent cohort of metastatic melanoma samples (n=36; 9 brain metastatic specimens). Then, we analyzed the trend of expression of those miRNAs during tumor progression by comparing their levels in primary tumors and their paired metastasis from patients with or without recurrence in the brain (n=18). Differential expression of some miRNAs was already evident at diagnosis in primary tumors that recurred in the brain, while for others it was acquired in the transition from primary to metastasis, suggesting that it may be a later event in tumor progression. Furthermore, in vitro modulation of specific signature miRNAs significantly altered the ability of melanoma cells to execute processes such as adhesion and transmigration through human brain endothelial cells and proliferation in human astrocytes conditioned media. Additionally, using an in vivo model of melanoma brain metastasis, we confirmed the capacity of specific miRNA alterations to promote melanoma cells’ competence to reach the brain. Finally, the analysis of potential downstream mediators of select miRNAs revealed the involvement of immuno-suppressive molecules, as well as inflammatory and chemotactic mediators in this process. Collectively, our results expand our understanding of the mechanisms that control melanoma brain metastasis, potentially revealing novel therapeutic avenues for patients for whom no viable approaches are currently available. 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 1946.
Lymphocytes control bone fracture healing by programming the mineralisation capacity of migratory osteogenic precursors
Authors: Alessandro Serra, Ireen Könnecke, Katharina Schmidt-Bleek, Hanna Schell, Andreas Radbruch, Georg Duda
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Inflammation of the bone microenvironment in arthritic conditions leads to extensive infiltration of immune cells causing destruction of articular cartilage and bone. Similarities characterise bone fracture. Here, sustained inflammation leads to synthesis of bone and cartilage, massive infiltration of hematopoietic cells and controlled tissue resorption terminating into net bone formation. Thus, to better understand how bone inflammation leads to successful repair instead of autoimmunity, the authors have drawn a comprehensive cellular study of post-fracture bone regeneration by confocal microscopy and other histological techniques. <h3>Materials and methods</h3> Experimental closed femoral fracture was used to induce bone regeneration in C57BL/six mice and congenic RAG <sup>−/−</sup> KO (lymphopenic), TCR βδ chain <sup>−/−</sup> KO (T cell deficient) and JHT <sup>−/−</sup> KO (B cell deficient) mice. Confocal microscopy was used to detect the presence of T, B, macrophages, eosinophils, activated osteoclasts, osteogenic precursors and osteblasts in the fracture callus. Histomorphometry was used to quantify bone regeneration. Cell culture was used to measure mineralisation capacity at steady state of bone marrow derived osteogenic precursors in WT and lymphopenic mice. <h3>Results</h3> Our data show that during fracture repair the majority of lymphocytes, macrophages and eosinophils appear late upon ensuing endochondral bone formation. Interestingly, lymphopenic mice had the capacity to mineralise cartilage and undergo subsequent resorption earlier than WT controls in vivo. Accordingly, by histomorphometric comparison of fracture repair in different immunodeficient animal models, the authors found that the speed of endochondral bone formation is T cell dependent. Confocal microscopy also showed that accelerated mineralisation in RAG mice occurred well before lymphocytes could be detected within the callus of WT animals. However, the authors clearly visualised in the callus of RAG and normal mice the concomitant immigration of osteogenic precursors from surrounding tissues. Remarkably, bone marrow osteogenic cells from RAG mice, taken in normal conditions, displayed abnormal mineralisation capacity than normal controls upon cell culture. This suggests that lymphocytes control bone regeneration by programming the basal activity and capacity to respond to damage of osteoblast precursors. <h3>Conclusions</h3> Bone repair involves the migration of bone marrow osteogenic precursors into the bloodstream to reach fracture sites. Immune cells infiltrate the fracture callus during the mid-late stages of bone regeneration and they consist mainly of B lymphocytes. T cells control the velocity of endochondral bone formation by programming the mineralisation capacity of osteogenic cells.
P232 The early detection of chronic obstructive pulmonary disease
Authors: A. Gupta, S. Church, S. Lacey
Journal: Thorax (2010)

<h3>Introduction</h3> Approximately 835 000 people in England have been diagnosed with COPD however it is estimated that over 3 million have the disease1 and those cases that are diagnosed are mainly moderate or severe in nature.2 The direct cost of COPD to the UK healthcare system is estimated to be between £810m and £930 m per annum<sup>3</sup> and without change is set to grow <h3>Methodology</h3> It is essential that we offer good quality early diagnosis but the numbers involved are huge so a screening programme and pathway were developed. Patients at risk of COPD were initially defined as being aged over 40 with a smoking history. Vitalograph COPD6 devices, which measure FEV<sub>1</sub> were used across 22 practices to screen the target population at an average test time of 5 min compared to full spirometry of 20 min. All abnormal results were followed up with full spirometry, performed by an accredited health care provider. <h3>Results</h3> To date 2055 patients have been screened. 841 (41%) demonstrated an abnormal result on COPD6 screening. Of these so far 376 have had COPD confirmed by spirometry. That is 18.3% of the target population and 45% of the group who had abnormal COPD6 results. It is estimated that, nationally over 2 million people have undiagnosed COPD and of those over 50% are diagnosed with moderate to severe disease2 however the results available to date suggest that early detection leads to the majority of patients being identified while their condition is still mild. Results to date demonstrate that 75% of diagnoses were mild, 18% moderate and 3.2% severe. We are still awaiting confirmation of the remaining 3.8%. The project is ongoing. <h3>Outcomes</h3> Mild COPD costs approximately 50% less to treat than moderate COPD and 90% less than severe COPD.<sup>4</sup> Therefore in addition to improving outcomes for patients, early detection will also reduce the burden of care to the NHS and socioeconomic costs.
P594 PROMOTION OF LIVER INJURY AND FIBROSIS BY THE LIVER-DERIVED PLASMA PROTEIN HISTIDINE-RICH GLYCOPROTEIN IS BASED ON POLARIZING HEPATIC MACROPHAGES TOWARDS THE INFLAMMATORY M1 PHENOTYPE
Authors: M. Bartneck, V. Fech, J. Ehling, X. Wei, K. Warzecha, K. Hittatiya, N. Gassler, T. Lammers, W. Jahnen-Dechent, C. Trautwein, F. Tacke
Journal: Journal of Hepatology (2014)
PTU-051 Post-Partum Defecatory Dysfunction: A Complex Problem Involving Co-Existing Faecal Incontinence and Rectal Evacuatory Disorder
Authors: E Horrocks, P Jordan, R Burgell, M Scott, C Knowles
Journal: Gut (2013)

<h3>Introduction</h3> Faecal incontinence and urgency are well-recognised sequelae of obstetric injury, however there is a paucity of literature describing the co-existence of symptoms of rectal evacuatory dysfunction (RED) and faecal incontinence (FI). This study aims to analyse and quantify these symptoms in patients referred for anorectal investigations following obstetric injury. <h3>Methods</h3> Consecutive patients undergoing specialist investigation at a tertiary referral unit following obstetric injury between 1st July 2010 and 31st July 2012 were identified. Symptoms at presentation were ascertained from the history. Patients routinely complete a Cleveland Clinic Constipation Score (CCCS) and Vaizey Incontinence score (VIS) prior to investigation. Symptoms volunteered by the patient were correlated with formal scoring systems to verify accuracy of symptom reporting and to study the co-existence of FI and RED. <h3>Results</h3> One hundred and sixty five women [median age 34 (range 19–55)] were included. Median parity was 2 [range 1–8]. Fourteen women (9.7%) had a 4th degree tear and 68 women (41%) a 3rd degree tear [106 (64%) occurring from the first vaginal delivery]. Three women requiring de-functioning stoma were excluded from further analysis. FI was volunteered in 87 women (54%), [59 urge FI (36%), 57 passive FI (35%) and 28 mixed FI (17%)]. Ninety women (56%) volunteered symptoms of RED. Co-existent symptoms of RED and FI were present in 58 women (36%). VIS and CCCS were available for 79 patients. Median VIS was 8 (IQR 4–13), and was significantly higher in those reporting FI symptoms [median score 11 (IQR 8–15)] than those not [median score 4 (IQR 0–8)] (p &lt; 0.0001 Mann Whitney U Test). Median CCCS was 8 (IQR 4–14), which was significantly higher in those reporting RED symptoms [median score 13 (IQR 11–17)] than those not [median score 5 (IQR 3–8)] (p &lt; 0.0001 Mann Whitney U Test). Fifty four patients (68%) had significant FI based on VIS (score &gt; 5) and 39 patients (49%) had significant RED based on CCCS (score &gt; 8). Thirty patients (38%) had scores compatible with significant co-existent FI and RED. <h3>Conclusion</h3> These results demonstrate symptoms of FI and RED often co-exist following obstetric injury regardless of method used to ascertain symptoms. A multi-modality treatment approach addressing overlapping pathophysiologies should be considered in these patients. <h3>Disclosure of Interest</h3> None Declared
THE CHARACTERISTICS OF IN-STENT RESTENOSIS AFTER DRUG ELUTING STENT IMPLANTATION IN FEMOROPOPLITEAL LESIONS AND 1-YEAR PROGNOSIS AFTER REPEAT ENDOVASCULAR THERAPY FOR THESE LESIONS
Authors: Osamu Iida, Mitsuyoshi Takahara, Yoshimitsu Soga, Keisuke Hirano, Yasutaka Yamauchi, Kan Zen, Daizo Kawasaki, Shinsuke Nanto, Hiroyoshi Yokoi, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2016)
Geoffrey Peter McMullin
Authors: T. Watson
Journal: BMJ (2014)

Peter McMullin died on Good Friday 2014 from complications after a mitral valve repair. He had been active until his last illness, playing golf regularly and working an allotment, but the leaking valve had severely reduced his mobility. He had approached the operation with some misgivings, fully aware of the risks of such a procedure at his age, but felt they were worth taking.

Peter entered Edinburgh medical school as a mature student, nearly 10 years older than his fellow students, and his maturity, quiet altruism, …
STREAMLINING INPATIENT COLONOSCOPY IN A TERTIARY CARE GI SERVICE
Authors: K Murphy, C Lahiff, P MacMathuna, J Leyden
Journal: Gut (2013)

<h3>Introduction</h3> Greater than 20% of all colonoscopies are associated with suboptimal bowel preparation,<sup>1</sup> resulting in lower caecal intubation rates, longer procedure times, decreased adenoma detection rates and higher costs.<sup>2</sup> Inadequate bowel cleansing is more common in hospitalized patients.<sup>3</sup> <h3>Aims/Background</h3> To critically analyse the utilisation of inpatient colonoscopy in a tertiary care university hospital. <h3>Method</h3> We performed a retrospective review of our electronic database for inpatient colonoscopies over a two month period from September to October 2012. Patient demographics, clinical details and key performance indicators were reviewed. Univariate and bivariate statistical analyses were performed using Mann Whitney and Fisher9s exact tests, where appropriate. <h3>Results</h3> Fifty six inpatient colonoscopies were performed during the study period. Twenty colonoscopies (36%) were normal and polyps were found in 15 (27%). There were 2 cancers (4%) and one high grade adenoma (2%). Fourteen (25%) colonoscopies were incomplete. Bowel preparation was suboptimal in 31 (56%) of cases. The reason for admission to hospital related primarily to a GI complaint in 23 (41%) of cases. These patients had significantly shorter median overall lengths of stay (10 versus 18 days, p=0.007) and time to colonoscopy (4 versus 10 days, p&lt;0.0001) when compared with patients admitted for non-GI reasons. No difference was seen in rates of pathology encountered in these patients but there was a trend towards better cancer detection rates (3/23, 13% versus 0/33, 0%; p=0.06). <h3>Conclusion</h3> We observed very high rates of inadequate bowel preparation and relatively low caecal intubation rates for inpatient colonoscopy. Cancer detection rates may be higher in patients admitted with GI complaints, although this needs to be confirmed by expansion of the cohort. The data suggest inpatient colonoscopy should be used sparingly and perhaps reserved for patients with primary GI complaints.
Further studies are needed on the prevention of postpolypectomy bleeding in pedunculated colonic polyps
Authors: Limei Ma, Zhining Fan
Journal: Endoscopy (2014)

We read with great interest the article by Ji et al., in which the authors compared the efficacy of prophylactic clip and endoloop application for the prevention of postpolypectomy bleeding in large pedunculated colonic polyps. The authors concluded that the clip was as effective and safe as the endoloop. We would like to make the following comments.
FRI0132 Insulin resistance is improved by tocilizumab therapy in rheumatoid arthritis: results from the toward study
Authors: H. Mirjafari, J. Wang, M. Klearman, O. Harari, I. Bruce
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Insulin resistance is increased in rheumatoid arthritis (RA). Reductions in inflammation, glucocorticoid therapy and disease-modifying anti-rheumatic drugs (DMARDs) have been associated with improvement in insulin resistance in patients with RA. <h3>Objectives</h3> To study whether tocilizumab (TCZ) therapy, an IL-6 receptor-inhibiting monoclonal antibody, improves insulin resistance in patients with RA. <h3>Methods</h3> TOWARD was a phase 3 study in patients with moderate to severe active RA on stable oral DMARDs that compared TCZ 8 mg/kg to placebo with 2:1 randomisation. Insulin resistance was calculated using the homeostatic model (HOMA-IR). Insulin resistance was classified as a HOMA-IR ≥2.2. Associations of baseline HOMA-IR against variables were analysed using linear regression. We examined associations between baseline HOMA-IR and baseline demographics, cardiovascular disease risk factors and disease-related factors using linear regression. Associations between change in HOMA-IR and change in RA disease parameters were also analysed using regression. <h3>Results</h3> Of the 1123 patients in the study, HOMA-IR could be calculated in 893 (79.5%). Median (IQR) age, glucose, insulin and HOMA-IR were 54 (46-62) years, 5.1 (4.6-5.6) mmol/l, 7.6 (4.6-12.6) µU/ml and 1.7 (1.0-2.9), respectively. 328 patients (37%) had insulin resistance. In an age- and gender-adjusted analysis, baseline HOMA-IR was associated with older age, higher BMI, SBP and DBP as well as IL-6 level (β-coefficient [95% CI]; 0.01 [0.01, 0.02] per pg/dl), RF positivity (0.25 [0.12, 0.38]) and lower IL-6 receptor levels (–0.02 [–0.02,–0.01] per ng/dl). HOMA-IR was reduced over 24 weeks in patients with insulin resistance who received TCZ but not in those who received placebo (Table). <h3>Image/graph</h3> <h3>Conclusions</h3> Insulin resistance is common in RA patients with inadequate response to DMARDs and is associated with RF positivity and IL-6 levels. In patients with pre-existing insulin resistance, HOMA-IR was significantly improved by TCZ therapy while unchanged by placebo. Understanding the mechanistic links between IL-6 and insulin regulation may provide an additional rationale for a stratified approach to using biologics to reduce cardiovascular disease risk in patients with RA. <h3>Disclosure of Interest</h3> H. Mirjafari Employee of: Roche Products Ltd, J. Wang Employee of: Roche Products Ltd, M. Klearman Employee of: Genentech, a member of the Roche group, O. Harari Employee of: Roche, I. Bruce Grant/research support from: UCB, Roche, GSK, Genzyme/Sanofi, Consultant for: Pfizer, UCB, GSK, Human Genome Sciences, Roche, Paid instructor for: Pfizer, UCB, GSK, Human Genome Sciences, Roche, Speakers bureau: Pfizer, UCB, GSK, Human Genome Sciences, Roche
A Model of Gonadotropin Regulation during the Menstrual Cycle in Women: Qualitative Features
Authors: P M Schlosser, J F Selgrade
Journal: Environmental Health Perspectives (2000)

Increasing concerns that environmental contaminants may disrupt the endocrine system require development of mathematical tools to predict the potential for such compounds to significantly alter human endocrine function. The endocrine system is largely self-regulating, compensating for moderate changes in dietary phytoestrogens (e.g., in soy products) and normal variations in physiology. However, severe changes in dietary or oral exposures or in health status (e.g., anorexia), can completely disrupt the menstrual cycle in women. Thus, risk assessment tools should account for normal regulation and its limits. We present a mathematical model for the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in women as a function of estrogen, progesterone, and inhibin blood levels. The model reproduces the time courses of LH and FSH during the menstrual cycle and correctly predicts observed effects of administered estrogen and progesterone on LH and FSH during clinical studies. The model should be useful for predicting effects of hormonally active substances, both in the pharmaceutical sciences and in toxicology and risk assessment.
P637Desmin null mouse as a possible experimental model of arrhythmogenic cardiomyopathy
Authors: N Athanasiadis, M Katsiboulas, C Dimitriou, I Kostavassili, M Mavroidis, CH Davos
Journal: Cardiovascular Research (2014)

Background: Desmin null mice (Des-/-) develop a multisystem disorder involving cardiac, skeletal, and smooth muscle. Myocardial abnormalities include progressive degeneration, cardiomyocyte death, extensive calcification and fibrosis which lead to a dilated cardiomyopathy pattern. The aim of this study is to investigate the presence of arrhythmias in a Des-/- mouse model as compared to wild type (WT) mice.
THU0552 Patients with Osteoarthritis have Better Functional Outcomes Compared to Rheumatoid Arthritis After Primary Hip Arthroplasty: A Cohort Study
Authors: J. A. Singh, D. Lewallen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pain and functional limitation are the main reasons for patients undergoing total hip arthroplasty <h3>Objectives</h3> To assess whether patient-reported outcomes (PROs) differ by underlying diagnosis in patients undergoing primary total hip arthroplasty (THA). <h3>Methods</h3> We used the prospectively collected data from the Mayo Clinic Total Joint Registry to assess the association of diagnosis with index knee functional improvement, moderate-severe pain and moderate-severe activity limitation at 2- and 5-year follow-up after primary THA using multivariable-adjusted logistic regression analyses. Odds ratios (OR) and 95% confidence intervals (CI) are presented. <h3>Results</h3> There were 7,139 primary THAs at 2-years and 4,234 at 5-years. In multivariable-adjusted analyses, at 2-year follow-up, compared to RA/inflammatory arthritis, OA were significantly associated with odds ratio (OR) [95% confidence interval (CI)] of moderate-severe activity limitation with OR 0.5 [95% CI: 0.3, 0.8] (p=0.01) at 2-years, but not at 5-years, OR of 0.7 (95% CI, 0.4, 1.4). There was no significant association of diagnosis with pain at 2- or 5-years. A diagnosis of avascular necrosis of bone (AVN) was associated with higher odds of moderate-severe pain with OR of 2.8 (95% CI, 0.9, 8.5; p=0.06) and 4.1 [95% CI: 1.2, 14.1] (p=0.02) at 5-years. No significant association of AVN with moderate-severe ADL limitation was noted at 2- or 5-years. <h3>Conclusions</h3> We found that patients with OA had better ADL outcomes compared to patients with RA/inflammatory arthritis, but similar pain outcomes after primary THA. AVN is associated with worse pain outcomes, but similar ADL outcomes compared to RA/inflammatory arthritis after primary THA. Insights into mediators of these relationships need to be investigated to understand how xxx influences outcomes after TKA. <h3>Disclosure of Interest</h3> None Declared