tbuckley/cabot-search huggingface dataset:
PB2207 EARLY SPLEEN RESPONSE IS A GOOD PROGNOSTIC FACTOR OF RUXOLINIB OUTCOME IN PATIENTS WITH MYELOFIBROSIS
Authors: E. Lomaia, N. Siordiya, G. Dimov, O. Senderova, M. Mihalev, A. Furtovskaya, O. Ochirova, O. Li, K. Trizna, A. Otmorskaya, E. Sokurova, A. Khazieva, A. Zaritskey
Journal: HemaSphere (2019)

Background: Ruxolitinib(RUXO) improves long‐term prognosis in patients(pts) with primary or post‐polycythemia/post‐thrombocythemia myelofibrosis(MF). The most patients experience spleen response. Meanwhile there are a few data how the speed of spleen response in MF affects RUXO treatment outcome. Aims: Evaluate prognostic significance of early spleen response on results of RUXO treatment in patients with MF and assess the factors associated with spleen response. Methods: In the multicenter real world ptactice study 42 patients (male 18, 43%) with MF and spleen data available at least at 3 months were included. Median age at the time of RUXO initiation was 55(25‐75)yrs. Median time from MF diagnosis to RUXO was 52(2‐346)mos. Median time on RUXO was 29 (4‐81)mos. Spleen response(SR) was assessed by palpation. Median spleen length before RUXO was 19(5‐33 cm) with massive spleen &gt;10 cm in the most pts ‐ 36(86%). Constitutional symptoms had 40(95%) of pts. DIPSS score was low, inter‐1 or inter‐2/high in 1(3%), 23(59%) and 15(38%) of 39 evaluable pts. Results: Spleen length reduction at 3mos was: &lt;25% in 13(31%)(Group 1), 25‐&lt;50% in 14(33%) (Group 2) and ≥50% in 15(36%)(Group 3) pts. At 6 mos 3/12(25%) and 3/14(21%) evaluable pts from Gr1 and Gr2 improved their SR. Some more pts from these groups experienced spleen reduction later, but mainly in case of RUXO dose elevation. SR, assessed according to IWG‐MRT criteria, was 13/42(31%) and 17/41(41,5%) in evaluable pts at 3mos and 6 mos, respectively. In all groups a few pts lost their SR. RUXO was stopped in 11(26%) pts, mainly due to disease progression or/and death. Depth of sSR significantly correlated with overall survival. All pts of Gr3 remained alive, whereas 7/29(24%) pts dead in Gr2 and Gr3 overall(p = 0,021). Less pts in Gr3 had huge spleen(&gt;20 cm), blasts 1% or more, low hemoglobin and were treated with low RUXO dose. There were equal symptoms burden in in different groups (Table 1). Summary/Conclusion: The majority of pts respond to RUXO. Depth of SR at 3 mos significantly influenced RUXO long term outcome – all pts with &gt;50% of spleen reduction at 3 mos are alive. It seems that pts with higher dose of RUXO, no periferal blasts, less spleen size and higher hemoglobin level are more responded to RUXO. Larger cohort of pts is needed to confirm statistical significance of this data. image
Abstract 17860: Cardiac Iodine-123 Metaiodobenzylguanidine Imaging Predicts Poor Prognosis Even in Patients Admitted With Acute Decompensated Heart Failure
Authors: Shunsuke Tamaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Sato, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Masatake Fukunami
Journal: Circulation (2015)

Introduction: Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging has been shown to provide prognostic information in patients with chronic heart failure. However, little is known about the prognostic value of cardiac MIBG imaging in patients admitted with acute decompensated heart failure (ADHF). Hypothesis: We assessed the hypothesis that cardiac MIBG imaging might also be useful for the prediction of poor clinical outcome in patients admitted with ADHF. Methods: We studied 115 consecutive patients admitted for ADHF from October 2011 to January 2013 and discharged with survival (age: 74±13 years, male: 56%, NYHA class at discharge: 2.2±0.8, left ventricular ejection fraction measured by echocardiography: 47.1±15.5%). Cardiac MIBG imaging, echocardiography and venous blood sampling were performed just before discharge. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate were calculated from the chest anterior view images obtained at 20 and 200min after isotope injection. The endpoints were unplanned hospitalization for worsening heart failure (WHF) and pump failure death (PFD). Results: During a follow-up period of 2.0±0.8 years, 32 patients had WHF and 15 patients had PFD. At multivariate Cox analysis, out of the variables including clinical, hemodynamic, biochemical, echocardiographic and MIBG parameters, H/M on delayed image (late H/M) was independently associated with WHF (p=0.0003) and PFD (p=0.0255), although brain natriuretic peptide showed the significant association with the endpoints at univariate analysis. Kaplan-Meier analysis showed that the patients with late H/M &lt;1.65 (mean value) had a significantly higher risk of both WHF and PFD than those with late H/M ≧1.65 (Figure). Conclusions: Cardiac MIBG imaging could predict poor outcome even in patients admitted with ADHF.
Abstract 244: Differential mRNA Expressions in Thoracic Aortic Aneurysm in Patients with Bicuspid and Tricuspid Aortic Valve
Authors: Yuanjia Zhu, Andrea Hanick, Mariah Wright, John Barnard, Eric E Roselli, David R Van Wagoner
Journal: Circulation Research (2016)

Objective: Bicuspid aortic valve (BAV), the most common congenital heart condition, is frequently associated with thoracic aortic aneurysm (TAA). Aortic mRNA expression patterns in BAV patients and expression differences between BAV and tricuspid aortic valve (TAV) patients are unclear. We sought to compare mRNA expressions in TAA in patients with BAV and TAV. Methods and Results: Ascending aorta tissue was obtained from 58 aortic aneurysm repair patients (31 BAV, 27 TAV) and from 8 heart transplant donors. Illumina Human HT-12v4 microarrays were used to assess mRNA expression. After standard QC and filtering, probes were analyzed using multivariable linear regression analysis, adjusting for age, gender, medication use (beta blockers, ACE-Is, ARBs), and 10 surrogate variables. Ingenuity Pathway Analysis (IPA) was used to identify pathways and top regulator effect networks that were differentially expressed in BAV vs. TAV and BAV vs. donors. In BAV vs. TAV, MMP9, ESM1 and IL1B were downregulated 0.63, 0.74 and 0.77 fold, whereas COMP was upregulated 2.29 fold (p &lt; 0.05 for all). In BAV vs. donors, IL1R2, MCEMP1, IL18RAP and ACAN were downregulated 0.66, 0.2, 0.2 and 0.05 fold, while ADAMTS8, CCL21 and CIDEA were upregulated 6.97, 6.24 and 4.65 fold (p &lt; 0.0001). IPA analysis showed P53 as the top upstream regulator for both BAV vs. TAV (p = 1.9e-8) and BAV vs. donors (p = 2.3e-25). IRF7, which protects against angiotensin II-induced hypertrophy in cardiomyocytes, was also a significant upstream regulator for BAV vs. TAV (p = 3.6e-7). Additionally, miR-124-3p in BAV vs. TAV (p = 6.3e-7) and BAV vs. donors (p = 1.7e-22), as well as miR-96-5p in BAV vs. TAV (p = 4e-7) were predicted significant upstream regulators. Immune response was shown to be the top regulator effect network in BAV vs. TAV, whereas perivascular fibrosis was shown to be an important regulator effect network in BAV vs. donors. Cell stress pathways were also activated in BAV vs. donors. Conclusions: Distinct pathways and regulator effect networks exist in TAA with BAV or TAV. TAV associated TAA is more associated with inflammatory responses, while BAV aortopathy is more associated with extracellular matrix remodelling and cell stress. MiRs may also play an important role in BAV aortopathy.
Mepolizumab failed to affect bullous pemphigoid: A randomized, placebo‐controlled, double‐blind phase 2 pilot study
Authors: Dagmar Simon, Shida Yousefi, Simone Cazzaniga, Christina Bürgler, Susanne Radonjic, Carine Houriet, Kristine Heidemeyer, Hans‐Wilhelm Klötgen, Evelyne Kozlowski, Luca Borradori, Hans‐Uwe Simon
Journal: Allergy (2019)

The authors declare that they have no conflicts of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Pathogenic Autoreactive T and B Cells Cross-React with Mimotopes Expressed by a Common Human Gut Commensal to Trigger Autoimmunity
Authors: William E. Ruff, Carina Dehner, Woo J. Kim, Odelya Pagovich, Cassyanne L. Aguiar, Andrew T. Yu, Alexander S. Roth, Silvio Manfredo Vieira, Christina Kriegel, Olamide Adeniyi, Melissa J. Mulla, Vikki M. Abrahams, William W. Kwok, Ruth Nussinov, Doruk Erkan, Andrew L. Goodman, Martin A. Kriegel
Journal: Cell Host & Microbe (2019)
Maintenance with Weekly Carfilzomib in Elderly Newly Diagnosed Multiple Myeloma (IFM 2012-03)
Authors: Arthur Bobin, Guillemette Fouquet, Alain Duhamel, Salomon Manier, Lionel Karlin, Brigitte Kolb, Mourad Tiab, Carla Araujo, Nathalie Meuleman, Jean Valère Malfuson, Pascal Bourquard, Pascal Lenain, Arnaud Jaccard, Karim Belhadj, Michel Attal, Philippe Moreau, Cyrille Hulin, Xavier Leleu
Journal: Blood (2019)
Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions
Authors: Somashekar G. Krishna, Phil A. Hart, Ahmad Malli, Andrew J. Kruger, Sean T. McCarthy, Samer El-Dika, Jon P. Walker, Mary E. Dillhoff, Andrei Manilchuk, Carl R. Schmidt, Timothy M. Pawlik, Kyle Porter, Christina A. Arnold, Zobeida Cruz-Monserrate, Darwin L. Conwell
Journal: Clinical Gastroenterology and Hepatology (2019)
Reflectance confocal microscopy confirms residual basal cell carcinoma on clinically negative biopsy sites before Mohs micrographic surgery: A prospective study
Authors: Cristian Navarrete-Dechent, Miguel Cordova, Saud Aleissa, Konstantinos Liopyris, Stephen W. Dusza, William Phillips, Anthony M. Rossi, Erica H. Lee, Ashfaq A. Marghoob, Kishwer S. Nehal
Journal: Journal of the American Academy of Dermatology (2019)
Survey of the translation shifts in hepatocellular carcinoma with ribosome profiling
Authors: Qin Zou, Zhengtao Xiao, Rongyao Huang, Xin Wang, Xun Wang, Haitao Zhao, Xuerui Yang
Journal: Theranostics (2019)

Despite the critical position of translation in the multilevel gene expression regulation program, high-resolution and genome-wide view of the landscape of RNA translation in solid tumors is still limited.Methods: With a ribosome profiling procedure optimized for solid tissue samples, we profiled the translatomes of liver tumors and their adjacent noncancerous normal liver tissues from 10 patients with hepatocellular carcinoma (HCC).A set of bioinformatics tools was then applied to these data for the mining of novel insights into the translation shifts in HCC.Results: This is the first translatome data resource for dissecting dysregulated translation in HCC at the sub-codon resolution.Based on our data, quantitative comparisons of mRNA translation rates yielded the genes and processes that were subjected to patient specific or universal dysregulations of translation efficiencies in tumors.For example, multiple proteins involved in extracellular matrix organization exhibited significant translational upregulation in tumors.We then experimentally validated the tumor-promoting functions of two such genes as examples: AGRN and VWA1.In addition, the data was also used for de novo annotation of the translatomes in tumors and normal tissues, including multiple types of novel non-canonical small ORFs, which would be a resource for further functional studies.Conclusions: The present study generates the first survey of the HCC translatome with ribosome profiling, which is an insightful data resource for dissecting the translatome shift in liver cancer, at sub-codon resolution.
Reduction of immunosuppressive tumor microenvironment in cholangiocarcinoma by ex vivo targeting immune checkpoint molecules
Authors: Guoying Zhou, Dave Sprengers, Shanta Mancham, Remco Erkens, Patrick P.C. Boor, Adriaan A. van Beek, Michail Doukas, Lisanne Noordam, Lucia Campos Carrascosa, Valeska de Ruiter, Roelof W.F. van Leeuwen, Wojciech G. Polak, Jeroen de Jonge, Bas Groot Koerkamp, Belle van Rosmalen, Thomas M. van Gulik, Joanne Verheij, Jan N.M. IJzermans, Marco J. Bruno, Jaap Kwekkeboom
Journal: Journal of Hepatology (2019)
OP0084 FRAGILITY HIP FRACTURES – DOES DESTINATION AFTER HOSPITAL DISCHARGE HAVE AN IMPACT ON PATIENT’S OUTCOME?
Authors: Miguel Guerra, Sara Ganhão, Francisca Aguiar, Raquel Ferreira, Teresa Martins-Rocha, Ana Filipa Águeda, Georgina Terroso, Carlos Vaz, Lúcia Costa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In Osteoporosis, hip fractures account for significant disease burden, with increased morbi-mortality. Because of this, patients are referred to rehabilitation and specific health care units, in order to regain autonomy and health. However, there is few evidence about patients' outcome, considering destination after inpatient discharge. <h3>Objectives</h3> To evaluate if destination after hospital discharge for a osteoporotic hip fracture has impact in the outcome (mortality and new fracture). <h3>Methods</h3> Patients referred to a Fracture Liaison Service from March 2015 until March 2017 with a fragility hip fracture were considered for this study. Clinical/demographic variables were retrospectively collected until January 2018, including destination at discharge (home, nursing home (NH), inpatient rehabilitation unit (RU)) and outcome (death, new fracture, lost to follow-up). Kaplan Meyer curves with log-rank test were used for statistical analysis (SPSS statistics 23); p&lt;=0.05 was considered statistically significant. <h3>Results</h3> From a total of 522 patients, 437 patients were discharged with a known destination: 58.1% to home (n=254), 27.7% to a RU and the remaining to a NH. Table 1 summarizes clinical and demographic characteristics of the sample. Seventy-four patients died (median time = 264 days, range 22-1049) and 43 suffered a new fracture (median time 301, 15-946); 129 patients maintained follow-up. Mortality rates within each group of discharged patients were: 15.4% in the group destined home, 22.6% in the group forwarded to a NH and 17.4% in those referred to a RU. No statistically significant difference was found in cumulative survivals between groups (figure 1A). The event refracture was observed in 10.2% of those discharged home, 6.5% in the group forwarded to a NH and 10.7% of those referred to a RU. Again, no statistically significant difference was observed (figure 1B). <h3>Conclusion</h3> Previous studies showed lower survival in patients discharged for conventional home care (1,2). In our cohort, despite more than half the sample was discharged home, no difference was found in mortality or re-fracture. Further studies will assist to clarify this matter. <h3>Reference</h3> [1] Pitzul KB, et al. Arch Osteoporos. 2017 Sep 30;12(1):87. <h3>Disclosure of Interests</h3> None declared
Detection of Pathways Affected by Positive Selection in Primate Lineages Ancestral to Humans
Authors: J.T. Daub, S. Moretti, I.I. Davydov, L. Excoffier, M. Robinson-Rechavi
Journal: Molecular Biology and Evolution (2017)

Gene set enrichment approaches have been increasingly successful in finding signals of recent polygenic selection in the human genome. In this study, we aim at detecting biological pathways affected by positive selection in more ancient human evolutionary history. Focusing on four branches of the primate tree that lead to modern humans, we tested all available protein coding gene trees of the Primates clade for signals of adaptation in these branches, using the likelihood-based branch site test of positive selection. The results of these locus-specific tests were then used as input for a gene set enrichment test, where whole pathways are globally scored for a signal of positive selection, instead of focusing only on outlier "significant" genes. We identified signals of positive selection in several pathways that are mainly involved in immune response, sensory perception, metabolism, and energy production. These pathway-level results are highly significant, even though there is no functional enrichment when only focusing on top scoring genes. Interestingly, several gene sets are found significant at multiple levels in the phylogeny, but different genes are responsible for the selection signal in the different branches. This suggests that the same function has been optimized in different ways at different times in primate evolution.
Erratum: Corrigendum: Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome)
Authors: Martin Zenker, Julia Mayerle, Markus M Lerch, Andreas Tagariello, Klaus Zerres, Peter R Durie, Matthias Beier, Georg Hülskamp, Celina Guzman, Helga Rehder, Frits A Beemer, Ben Hamel, Philippe Vanlieferinghen, Ruth Gershoni-Baruch, Marta W Vieira, Miroslav Dumic, Ron Auslender, Vera L Gil-da-Silva-Lopes, Simone Steinlicht, Manfred Rauh, Stavit A Shalev, Christian Thiel, Arif B Ekici, Andreas Winterpacht, Yong Tae Kwon, Alexander Varshavsky, André Reis
Journal: Nature Genetics (2006)
Hexokinase-2 Glycolytic Overload in Diabetes and Ischemia–Reperfusion Injury
Authors: Naila Rabbani, Paul J. Thornalley
Journal: Trends in Endocrinology and Metabolism (2019)

HighlightsHK2 produces increased metabolic flux through glycolysis in hyperglycemia through glucose-mediated stabilization of HK2 to proteolysis.This produces abnormal increases in glycolytic intermediates or glycolytic overload, driving mitochondrial dysfunction and activation of hexosamine, protein kinase C, and dicarbonyl stress pathways.HK2-linked glycolytic overload explains tissue-specific pathogenesis in diabetes linked to vascular complications and contributes to pathogenesis in ischemia–reperfusion injury and cell senescence.This new pathogenic mechanism hypothesis suggested new targets for therapeutic development that gave promising outcomes in initial clinical evaluation.AbstractHexokinase-2 (HK2) was recently found to produce increased metabolic flux through glycolysis in hyperglycemia without concurrent transcriptional or other functional regulation. Rather, stabilization to proteolysis by increased glucose substrate binding produced unscheduled increased glucose metabolism in response to high cytosolic glucose concentration. This produces abnormal increases in glycolytic intermediates or glycolytic overload, driving cell dysfunction and vulnerability to the damaging effects of hyperglycemia in diabetes, explaining tissue-specific pathogenesis. Glycolytic overload is also activated in ischemia–reperfusion injury and cell senescence. A further key feature is HK2 displacement from mitochondria by increased glucose-6-phosphate concentration, inducing mitochondrial dysfunction and oxidative stress. This pathogenic mechanism suggested new targets for therapeutics development that gave promising outcomes in initial clinical evaluation.
FRI0295 EVALUATION OF CLINICAL CHARACTERISTICS IN BEHCET SYNDROME BY GENDER AND AGE; A SINGLE CENTER EXPERIENCE WITH 665 PATIENTS
Authors: Murat Torgutalp, Serdar Sezer, Müçteba Enes Yayla, Ayse Bahar Kelesoglu Dincer, Emine Gzde Aydemir Glksz, Didem Sahin Eroglu, Tahsin Murat Turgay, Gülay Kınıklı, Askin Ates
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> To evaluate clinical characteristics according to age and gender in patients with Behcet's Syndrome (BS). <h3>Objectives</h3> BS is a systemic vasculitis that affects mucosa, skin, joint, eye, vessels, gastrointestinal system, and central nervous system. The disease characterizes by relapses and remissions, and it is known that prognosis is worse in young males. The aim of this study was to reinvestigate the relationship between the clinical features of BS according to gender and age. <h3>Methods</h3> The data of 665 patients (282 male, 383 female), diagnosed as BS according to the ISG-1990 Behçet's Disease classification criteria, were retrospectively evaluated. <h3>Results</h3> All patients had oral aphthous (OA) ulcers (100%). Eighty-five percent of patients had a genital ulcer (GU), 56.5% had erythema nodosum (EN), 65.9% had papulopustular lesions (PPL), 32.6% had ocular involvement, 49.3% had joint involvement, and 21.7% vascular involvement, and 4.8% had neurobehcet. The incidence rates of PPL, ocular involvement, and vascular involvement were significantly higher in males (p &lt;0.001, p = 0.004 and p &lt;0.001, respectively). GU, joint involvement, headache, and pathergy positivity were more common in women (p = 0.006, p &lt;0.001, p &lt;0.001 and p &lt;0.001, respectively). Table 1 shows the comparison of the clinical features according to gender. When we compare the mean age of the patients according to the presence or absence of clinical findings; patients with GU, EN, and vascular involvement were found to be younger than those without (p = 0.006, p = 0.025 and p = 0.007, respectively) (Table-2). <h3>Conclusion</h3> Clinical features of BS may vary according to age and gender. Variations can be observed depending on the size of the population, the center where the study is conducted, and the selected-criteria for inclusion. In our study, PPL, ocular involvement and vascular involvement were more frequent in men, whereas GU, joint involvement, headache, and pathergy positivity were more common in women. In addition, GU, EN, and vascular involvement were related to younger ages. Our results were compatible with the BS literature. <h3>References</h3> None <h3>Disclosure of Interests</h3> None declared
Comparison of the 5637 human urothelial cancer cell line with a second-generation 5637 cell line for cancer therapy
Authors: Weiguo Jian, Hideyuki Yamashita, Deandra Cardenas, Guru Sonpavde, Seth Lerner
Journal: Cancer Research (2008)

2711  Objective: Obtaining stable preclinical animal models with 5637, an invasive human urothelial cancer cell line, is difficult. The purpose of this study was to examine a regenerated 5637 cell line and evaluate the possible development of human urothelial cancer models with the cell line in nude mice.  Materials and methods:  The 5637 cell line, which is derived from muscle-invasive human urothelial cancer, was purchased from the ATCC (Manassas, VA), and a total of 25 athymic 5-6 week old female nude mice (Harlan) were employed. To generate a second-generation 5637 cell line, 1x107 5637 parental cells were inoculated subcutaneously in nude mice. Ten days after implantation, the tumors were harvested. Tumor tissue was cut and minced and then cultured in the medium. We usd the regenerated 5637 cell line to evaluate biologic agents (enzastaurin, dasatinib), chemotherapy (cisplatin, gemcitabine) and gene therapy (Ad5F35TK/GCV) in vitro, and in subcutaneous xenogaft and orthotopic murine models. The orthotopic model was established with 5 to 6 week-old female athymic nude mice that were anesthetized and a 24-gauge angiocatheter was inserted into the bladder through the urethra. One hundred microliter of 0.25% trypsin in 0.02% EDTA was infused and retained in the bladder for 30 min. The bladder was then recatheterized and rinsed with phosphate-buffered saline. A 100 l cell suspension containing 1x107 generated 5637 cell mixed with matrigel (1:1) were instilled into the bladder. The urethra was ligated with a clip for 1 hr. All animals were euthanized after 4-6 weeks and tumors were removed for histology analysis.  Results:  All of the agents evaluated induced apoptosis and inhibited proliferation in parental as well as generated 5637 cell lines in vitro. Subcutaneous xenograft tumors established with generated 5637 cells grew in a larger proportion of animals compared to parental 5637 cells. Orthotopic 5637 tumors were also established in a high proportion of animals in the bladder with the generated 5637 cells, while our earlier attempts at establishing an orthotopic model with parental 5637 cells were unsuccessful.  Conclusion: A second-generation invasive bladder cancer 5637 cell-line derived from xenograft tumors provides a robust preclinical system for the evaluation of a variety of therapeutic agents.