tbuckley/cabot-search huggingface dataset:
OC-080 Low-grade dysplasia in ulcerative colitis: risk factors associated with progression to high-grade dysplasia or colorectal cancer: Abstract OC-080 Table 1
Authors: RCH Choi, A Ignjatovic-Wilson, M Rutter, S Thomas-Gibson, J Warusavitarne, B Saunders, T Graham, AL Hart
Journal: Gut (2015)

<h3>Introduction</h3> The aim of this study was to identify risk factors associated with development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD). <h3>Method</h3> Patients with histologically confirmed extensive UC who were diagnosed with LGD between 1993 and 2012 were identified and followed up to 1<sup>st</sup>January 2013. Data on patient demographics, endoscopic and histological variables at the time of the first LGD episode were collected and correlated with progression to HGD or CRC, our primary outcome measure. Time to event analysis was performed using Cox-proportional hazards methods. <h3>Results</h3> A total of 172 patients were followed for median of 48 months (interquartile range (IQR), 15–87) who underwent 707 follow-up colonoscopies (median, 4; IQR, 2–6) after the initial LGD episode. Overall, 33 patients developed HGD or CRC (19.1%) during study period. Table 1shows variables significantly associated with progression to HGD/CRC on univariate analysis. At multivariate level, only macroscopically non-polypoid (HR, 8.6; 95% CI, 3.0–24.8; <i>p </i>&lt; 0.001) or invisible (HR, 4.1; 95% CI, 1.3–13.4; <i>p = 0</i>.02) lesions, lesions ≥1 cm in size (HR, 3.8; 95% CI, 1.5–13.4; <i>p = 0</i>.01), and a previous history of indefinite for dysplasia diagnosis (HR, 2.8; 95% CI, 1.2–6.5; <i>P = 0</i>.01) remained significant contributory factors for developing HGD/CRC. The detection rate for non-polypoid lesions was significantly higher with chromoendoscopy (15.8%) compared with white-light endoscopy (7.8%; <i>p </i>&lt; 0.001). <h3>Conclusion</h3> The chromoendoscopy was superior at detecting non-polypoid lesions compared with the white-light endoscopy. Lesions that are large (≥1 cm), non-polypoid, and endoscopically invisible or preceded by “indefinite for dysplasia” diagnosis are independent risk factors for the development of HGD/CRC. <h3>Disclosure of interest</h3> None Declared.
Abstract 1081: Activity of microRNA replacement reagent, MRX34, in multiple myeloma <i>in vivo</i> model
Authors: Woo June Jung, Youngil Koh, Sinil Kim, Hyejoo Park, Sung-Soo Yoon
Journal: Cancer Research (2016)

Abstract Background: Despite recent progress in multiple myeloma (MM) treatment with the advent of new targeted anticancer agents such as Bortezomib, Lenalidomide and, Thalidomide MM still remains incurable. To improve clinical outcome of MM patients, many research have been trying to develop novel targeted drugs. Recent studies demonstrated that microRNA Replacement reagent could be a promising therapeutic strategy in patients with hematologic malignancies. Hence, we tried to examine the efficacy of MRX34, a microRNA-34 replacement reagent, in MM animal model. Methods: We examined the anti-tumor activity of a MRX34 against 3MM cell lines (LP1, MOLP-8, and U266), and investigated the survival effects through which this novel agent shows anti-MM activity. For an animal study, we used NRG (NOD-Rag1null IL2rgnull, CB-17 SCID) mice that were injected with MM cells via tail vein. MOLP-8, LP1 and U266 cells were injected Intravenous 106 cells of NRG. When tumors were measurable, mice were assigned to 3 treatment groups receiving the vehicle alone (control), MRX34 0.3mg/kg treatment group and, MRX34 1mg/kg treatment group were given Intravenous 5 times a week. Results: Median survival of mice injected with LP1, MOLP-8 and U266 cell lines were 28days, 29 days and 34days respectively without any treatment. When mice were treated with MRX-34, median survival was 33days, 37days and 42days respectively. There was a significant survival advantage with MRX-34 treatment in MOLP-8 and U266 cell lines. For monoclonal proteins, mice treated with MRX34 group are suppressed M-protein level almost 30% less than M-protein. Summary / Conclusion: Our data indicated that MRX34 had beneficial effects in multiple myeloma animal model. Mice treated with MRX34 showed M-protein suppression and survival advantage. Our results warrant further clinical studies using this novel agent in MM. Citation Format: Woo June Jung, Youngil Koh, Sinil Kim, Hyejoo Park, Sung-Soo Yoon. Activity of microRNA replacement reagent, MRX34, in multiple myeloma in vivo model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1081.
Lenalidomide Response in Relapsed/Refractory Diffuse Large B-Cell Non-Hodgkin’s Lymphoma.
Authors: Izidore S. Lossos, Peter H. Wiernik, Glen Justice, Joseph M. Tuscano, Craig E. Cole, Julie M. Vose, Dennis Pietronigro, Kenichi Takeshita, Annette Ervin-Haynes, Jerome B. Zeldis, Thomas M. Habermann
Journal: Blood (2007)
C13orf31 (FAMIN) is a central regulator of immunometabolic function
Authors: M Zaeem Cader, Katharina Boroviak, Qifeng Zhang, Ghazaleh Assadi, Sarah L Kempster, Gavin W Sewell, Svetlana Saveljeva, Jonathan W Ashcroft, Simon Clare, Subhankar Mukhopadhyay, Karen P Brown, Markus Tschurtschenthaler, Tim Raine, Brendan Doe, Edwin R Chilvers, Jules L Griffin, Nicole C Kaneider, R Andres Floto, Mauro D'Amato, Allan Bradley, Michael J O Wakelam, Gordon Dougan, Arthur Kaser
Journal: Nature Immunology (2016)
Abstract 19170: Coronary Artery Calcium Score in Patients With Heterozygous Familial Hypercholesterolemia is Proportional to Lifetime LDL Burden After up to 28 Years of Treatment
Authors: P. Barton Duell
Journal: Circulation (2013)

Heterozygous familial hypercholesterolemia (FH) is associated with severe hypercholesterolemia and early onset of CVD. Prior studies have demonstrated elevated coronary artery calcium deposition in FH. Initiation of treatment as early as age 8-12 years is presumed to help prevent cardiovascular complications. Hypothesis: Long-term LDL-lowering treatment will reduce accumulation of coronary artery calcium (CAC) in FH. Methods: Cross-sectional analysis of data from 28 patients with heterozygous FH and no prior diagnosis of CVD who had a CAC score measurement. Results: Twenty-eight subjects treated in our University Lipid Disorders Clinic for 0-28 years were studied (current age 58 +/- 11 years, 18 women, pre-treatment LDL cholesterol (C) 245 +/- 93, lipoprotein(a) 72 +/- 104, current CAC score 210 +/- 464, CAC percentile 55 +/- 38). The cumulative lifetime LDL burden was proportional to the age treatment was initiated (r=0.47, P=0.013). The CAC score was proportional to age (r=0.52, P=0.026) and cumulative LDL burden (r=0.71, r=0.0016), and was higher in men vs women (442 +/- 721 vs 81 +/- 129, P=0.046). HDL-C, triglycerides, and lp(a) were not correlated with CAC scores. Nine patients treated &gt; 15 years had an achieved LDL-C 105 +/- 40 compared to 202 +/- in 11 patients treated &lt; 1 year. The long term group initiated aggressive treatment at an average age 21 years younger than the short term group (mean age 38 +/- 15 [range 20-67] vs 59 +/- 11 [range 43-71]; P=0.024). Despite these differences, many long-term patients had elevated CAC scores (33% &gt; 400) after up to 28 years of treatment. Summary: CAC scores, which are a marker for atherosclerotic plaque accumulation (but calcium may be absent in about 50% of plaques in patients with FH) are proportional to age and lifetime LDL burden in patients with FH, but elevated CAC scores are prevalent even after long-term aggressive LDL-lowering therapy beginning at a mean age of 38 years. Conclusions: These findings indicate that patients with heterozygous familial hypercholesterolemia warrant aggressive LDL lowering initiated at a young age.
Abstract 2158: Pharmacologic, pharmacodynamic action of MELK kinase inhibitor OTS167 in cancer cells
Authors: Suyoun Chung, Kyoko Kijima, Yosuke Harada, Naofumi Takamatsu, Takashi Miyamoto, Yo Matsuo, Yusuke Nakamura
Journal: Cancer Research (2016)

Abstract Cancer is the second most common cause of death in US in 2015 and has been the leading cause of death in Japan since 1981. Despite of improved therapeutic strategies in cancer, only limited treatment options can still be available to a subset of patients. Many efforts have been made to develop molecular targeted drugs, but the success rate did not reach to patients’ expectation. Unlike the conventional chemotherapy, the use of maximum tolerated dose (MTD) and the measurement of bulk tumor volume are not always appropriate for the clinical evaluation of molecular targeted drugs. To optimize and personalize the dosing for targeted agents, detailed molecular pathway and biomarkers that are affected by the drug should be elucidated. OTS167 was developed as a novel and potent MELK kinase inhibitor that we previously reported. The expression of MELK is elevated in various human cancers both in solid and hematological tumor and MELK is known to be associated with cancer progression and poor prognosis. Because MELK is indicated its critical roles in cancer stem cell proliferation as well, targeting MELK is an attractive and promising therapeutic strategy for cancer patient. Here, we report the molecular mechanism of action of OTS167 in preclinical model. OTS167 suppressed MELK activity and promoted MELK protein degradation by inhibition of autophosphorylation. OTS167-treated cells showed drastic morphological transformation with the induction of p53 and p21 expression. We also investigated the expression of stem cell markers to elucidate whether OTS167 suppresses cancer stem-like properties through inhibition of MELK. Furthermore, we evaluated antitumor activity of OTS167 using human xenograft model and molecular changes in tumor tissue. The expression of MELK and downstream molecules were decreased in OTS167-treated xenograft tumor tissues by IHC. The change of expression and pharmacological effect were well correlated. Our data provide the evidence for the concept that OTS167 suppresses tumor growth through the inhibition of MELK signaling pathway and suggest the possibility of biomarkers for the assessment of clinical efficacy. Citation Format: Suyoun Chung, Kyoko Kijima, Yosuke Harada, Naofumi Takamatsu, Takashi Miyamoto, Yo Matsuo, Yusuke Nakamura. Pharmacologic, pharmacodynamic action of MELK kinase inhibitor OTS167 in cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2158.
Is there an association between study size and reporting of study quality in dermatological clinical trials? A meta-epidemiological review
Authors: S. Ratib, S.R. Wilkes, M.J. Grainge, K.S. Thomas, C. Tobinska, H.C. Williams
Journal: British Journal of Dermatology (2016)

Clinicians engaged in evidence-based medicine often have to base treatment decisions on randomised clinical trials (RCTs) with small sizes. 1 The choice of sample size is influenced by a number of factors including power, magnitude of difference anticipated, alpha, study design and whether the objective of the trial is equivalence or superiority.Based on our experience of reviewing hundreds of dermatological clinical trials, we hypothesized that sample size could be a crude surrogate of study quality in that larger studies are of generally better quality than smaller ones.Given the substantial evidence that some specific trial characteristics such as allocation concealment may influence treatment effect, 1,2,3 knowledge of study quality before implementing trial results into clinical practice is important.We therefore aimed to examine if there is an association between sample size and risk-of-bias assessment in RCTs included in published Cochrane skin reviews.The Cochrane risk-of-bias tool focusses on whether key items, known to be empirically associated with distortion of treatment effect, are reported or not. 3,4We therefore refer to 'reporting of study quality' as a proxy for formal study quality.
P0815 : Cost-effectiveness of treating different stages of genotype 1 hepatitis C Virus (HCV) with AbbVie 3D (ABT-450/ritonavir/ombitasvir and dasabuvir) +/− ribavirin compared to no treatment in the United States
Authors: S.J. Johnson, D.A. Misurski, T.R. Juday, J.C. Samp, S.E. Marx, H. Parisé, S. Virabhak, S. Saab
Journal: Journal of Hepatology (2015)
Medicine and books: Body Horror: Photojournalism, Catastrophe and War
Authors: Abi Berger
Journal: BMJ (1998)

John Taylor 

Manchester University Press, £15.99, pp 210 

ISBN 0 7190 3722 0 

The thing about looking at photographs is that we have a choice of whether to engage with the event depicted or not. We may have little concept of what preceded the picture being taken or what happened immediately afterwards, but we can look with utter detachment or we can get involved. Much of Body Horror discusses the apparent sanitisation of war and other traumatic situations by the media’s adoption of policies designed more to protect the viewer than to portray reality. Yet, for a book about photography, there are frustratingly few pictures included, and, although the subject matter is fascinating, it not an easy read. 

Throughout the book Taylor suggests that we are likely to be minimising the atrocities of war and disaster by allowing only ethically acceptable photographs to be published, and that we would be more appropriately shocked out of complacency if starker images were splashed across our newspapers. He argues that other nations’ wars and famines could become more our own if we had to face death and destruction rather than the more visually acceptable—but less shocking—alternatives that have come to replace them. Emotive they may be, but better this than bland anaesthesia which sedates and numbs our senses. On the other side of the debate, however, there are those who argue strongly that the persistent use of shocking pictures can induce an analgesic effect and “compassion fatigue,” such that the desired acknowledgement of horror is replaced by “It’s only a photograph.” 

Taylor quotes Martin Bell, the former BBC reporter: “In a world where genocide has returned in recent years to haunt three continents, we should remind ourselves that this crime against humanity requires accomplices—not only the hatred that makes it happen, but the indifference that lets it happen.” It is this indifference and lack of imagination that Taylor and others suggest can come from an inappropriate use of photography. As another critic says, “If we cannot imagine torture, we cannot stop it.” 

In chapter 3 Taylor himself adopts an interesting policy of journalistic self censorship in an effort to reduce gratuitously repulsive material. Rather than printing the actual pictures, he uses words to describe a series of photographs that depict a particularly gruesome execution. But by adopting this method, he ironically creates a far more vivid picture than I suspect the original photographs would have done. I felt physically sickened by his choice of words because they told the story of the execution from start to finish, leaving absolutely nothing to the imagination. Publishing the photographs alongside the text may have drawn me in, but printing them on their own—suspended in midair without text—would almost certainly have been less powerful.
Abstract 3934: Analysis of PKC-ζ protein and mRNA levels in normal and malignant breast tissue
Authors: Christopher Apostolatos, Tracess Smalley, Mildred A. Duncan
Journal: Cancer Research (2016)

Abstract It is estimated that in 2015 breast cancer will be the second leading cause of cancer death in women. For this purpose, biochemical markers for breast cancer have been investigated, to assist in early detection and more accurate diagnoses. In breast cancer tissue, the atypical isozyme of protein kinase C zeta, PKC-ζ, has been a topic in research; It has been shown that an overexpression of this protein may be indicative of developing carcinogenesis and contributes to proliferation through the NF kappa B pathway, which is a stress-regulated switch for cell survival. In this investigation, the expression of PKC-ζ was analyzed in normal and malignant female human breast tissue samples by Western blot, immunoprecipitation and PCR. In the preliminary results, the malignant breast tissue samples illustrated a significant expression of PKC ζ when compared to the expression of PKC-ζ in normal breast tissue samples. The same tissues were also processed for total RNA isolation which was followed by cDNA synthesis and Real Time PCR. The level of PKC-ζ mRNA was tested and no overexpression was observed in either malignant or normal breast tissue samples. While protein studies may suggest that PKC-ζ could be considered a biomarker for breast cancer, the same cannot be said about mRNA levels. The overexpression of PKC-ζ protein level and the normal PKC-ζ mRNA level are indicators of possible miRNA activity that may regulate translation in malignant tissues but not the normal. Citation Format: Christopher Apostolatos, Tracess Smalley, Mildred A. Duncan. Analysis of PKC-ζ protein and mRNA levels in normal and malignant breast tissue. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3934.
Telomere Shortening and Genomic Instability: Primary Cells from Patients with Telomere Repair Complex Mutations Are Susceptible to End-to-End Chromosome Fusion and Aneuploidy.
Authors: Elaine M. Sloand, Rodrigo Calado, Simant Shah, Loretta Pfannes, Jan Blancato, Neal Young
Journal: Blood (2006)
Outcome After Admission at Veterans Affairs vs Non–Veterans Affairs Hospitals—Reply
Authors: Sudhakar V. Nuti, Li Qin, Harlan M. Krumholz
Journal: JAMA (2016)

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Abstract 1276: Pannexin 1 regulates rhabdomyosarcoma tumor growth: a potential novel therapeutic target
Authors: Xiao Xiang, Stephanie Langlois, Marie-Eve St-Pierre, Jessica Barre, Tammy Le Pham, Kyle N. Cowan
Journal: Cancer Research (2016)

Abstract Rhabdomyosarcoma (RMS) is a skeletal muscle-derived soft tissue sarcoma for which a novel therapeutic strategy is greatly needed. RMS cells have lost the ability to terminally differentiate thus proliferating indefinitely. Promoting their redifferentiation to skeletal muscle tissue is thus a promising therapeutic approach. We have recently shown that levels of Pannexin 1 (Panx1) are below detectable limits in undifferentiated myoblasts, but become highly upregulated during their differentiation and indeed promote this process. We thus hypothesize that the levels of Panx1 are deregulated in RMS and that restoration of Panx1 levels may induce differentiation of RMS cells thereby alleviating their malignant properties. Briefly, our results demonstrate that both Panx1 transcript and protein are at very low levels in, both embryonal and alveolar RMS tumor specimens and patient-derived cell lines similar to that seen in fetal skeletal muscle tissue and undifferentiated myoblasts, respectively. In vitro functional analyses have revealed that while re-introduction of Panx1 in RMS cell lines led to their partial differentiation, it significantly inhibited their rate of proliferation and migration. Moreover, re-expression of Panx1 in RMS cell lines prevented both spheroid formation and growth, and induced RMS cell apoptosis. Based on this in vitro data, pre-clinical orthotopic xenograft studies are currently underway to assess the ability of Panx1 to inhibit tumor onset and growth, and induce tumor regression in vivo. Our preliminary results thus far have shown that Panx1 over-expression significantly suppresses RMS xenograft tumor growth. Taken together, these results indicate that restoration of Panx1 levels in RMS reduces its malignant properties. This, together with further investigation into the tumor-suppressive mechanism by which Panx1 mediates its effects, will establish Panx1 as a novel therapeutic target for RMS. Citation Format: Xiao Xiang, Stephanie Langlois, Marie-Eve St-Pierre, Jessica Barre, Tammy Le Pham, Kyle N. Cowan. Pannexin 1 regulates rhabdomyosarcoma tumor growth: a potential novel therapeutic target. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1276.
Perspectives on Some Controversies in Cardiovascular Disease Risk Assessment in the Pharmaceutical Development of Glucose-Lowering Medications
Authors: Byron J. Hoogwerf, David H. Manner, Haoda Fu, Elena Moscarelli, Brenda L. Gaydos, Robert J. Heine
Journal: Diabetes Care (2016)

The U.S. Food and Drug Administration (FDA) issued guidance on requirements to assess cardiovascular disease (CVD) risk with drugs being developed for approval for clinical use. The guidance was triggered by a meta-analysis published by Nissen and Wolski that suggested an increased risk for myocardial infarction with the use of rosiglitazone. This article discusses controversies around CVD trials in diabetes beginning with the University Group Diabetes Program. This is followed by a brief description of the FDA guidance for evaluating CVD risk with glucose-lowering medications. Limitations of meta-analyses of data from phase 2 and 3 (phase 2/3) trials to inform CVD risk are highlighted. These include the differences between patient characteristics in phase 2/3 trials and those in cardiovascular outcome trials (CVOTs) and the relatively short exposure time in phase 2/3 trials. The differences may partly explain the observed disparity between phase 2/3 meta-analyses and the results of completed CVOTs. Approaches to understanding CVD risk with a new medication should get to the answer about risk as efficiently as possible to minimize any potential harm to patients. In that context, we discuss options for clinical trial design and an alternative approach for statistical analyses.
Four in Florida are infected with Zika from local mosquitoes
Authors: Michael McCarthy
Journal: BMJ (2016)

Health officials in Florida have identified four cases of Zika virus disease that were probably caused by bites from local Aedes aegypti mosquitoes.

The US Centers for Disease Control and Prevention (CDC) said on Friday 29 July that the cases were the first evidence that mosquitoes in the United States have been infected by the virus.

“The bottom line here is that Zika is now present in the continental United States,” said Tom Frieden, CDC director, who warned that other outbreaks in the US should be expected. “Everyone, particularly pregnant …