tbuckley/cabot-search huggingface dataset:
QOL-38. WILL ELECTRONIC INTEGRATED TEXT, VISUAL AND AUDIO QUESTIONNAIRE BE A BETTER TOOL TO EVALUATE THE HEALTH STATUS OF PAEDIATRIC HYDROCEPHALUS PATIENTS?
Authors: Alf Nicholson, John Caird, Joy Tan
Journal: Neuro-Oncology (2018)

The Electronic Integrated Text, Visual and Audio Questionnaire (EITVAQ) was designed towards developing a disease-specific tool to measure child health status from a child’s perspective. EITVAQ’s outcome is anticipated to be positive, introducing a child-friendly health measurement tool. This was a prospective crossover pilot study that compared EITVAQ to a printed text 2-paged paper questionnaire (TEXT) format quality of life questionnaire in paediatric hydrocephalus patients. The study was conducted from November 2015 to June 2016 in the Neurosurgical Outpatient Department, Temple Street, Children University Hospital. Data was compiled for both EITVAQ and TEXT and analyzed using Software Package using Statistical Analysis (SPSS). There was a 100% rate of completion for EITVAQ. However, only 9 (37.5%) of the patients managed to complete the text format. The mean time to complete EITVAQ was 7 minutes. There are 32 questions found in EITVAQ. The mean score for EITVAQ was 132.92 (83%) satisfactory score. Using Pearson Chi-Square Test, the P-Value is 0.341. Although this is not a significantly substantial value, however, patient with less surgical procedure were able to complete EITVAQ 18.9% more than patient with more than 5 surgical procedures. Furthermore, there was no real correlation between the gross motor function classification system (GMFCS) score and the inability to complete the TEXT format. In this study, the results support that EITVAQ is a better tool to evaluate the health status of paediatric hydrocephalus patients as it is tailored according to their disability needs.
Effect of combination of proteasome inhibitor marizomib and immunomodulatory agent pomalidomide on synergistic cytotoxicity in multiple myeloma.
Authors: Dharminder Chauhan, Deepika Sharma Das, Arghya Ray, Paul G. Richardson, Mohit Trikha, Kenneth Carl Anderson
Journal: Journal of Clinical Oncology (2014)

8588 Background: Our prior studies showed that the proteasome inhibitor marizomib, distinct from bortezomib, triggers apoptosis in multiple myeloma (MM) cells resistant to bortezomib, and induces synergistic anti-MM activity in combination with immunomodulatory agent lenalidomide. Like lenalidomide, pomalidomide is an analogue of thalidomide, has immunomodulatory properties, and has been approved by FDA for treatment of MM. The approved indication for pomalidomide is for MM patients who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified. Here, we examined the combined anti-MM activity of marizomib and pomalidomide using in vitro models of MM. Methods: MM cell lines, patient MM cells, and PBMCs from normal healthy donors were utilized to assess the synergistic anti-MM activity of marizomib and pomalidomide. Results: MM cells were pretreated with DMSO control or with pomalidomide for 24h; marizomib was then added for an additional 24h, followed by analysis of cell viability. A significant decrease in viability of all cell lines was observed in response to treatment with combined low doses of marizomib and pomalidomide, compared with either agent alone. Isobologram analysis confirmed the synergistic anti-MM activity of these agents. The cytotoxicity of combination therapy was observed in MM cells resistant to bortezomib therapies. Marizomib plus pomalidomide-induced apoptosis was associated with: 1) activation of caspase-8, caspase-9, caspase-3, and PARP; 2) downregulation of IRF4, c-myc, and Mcl-1; 3) inhibition of migration of MM cells and angiogenesis; and 4) suppression of proteasome activity. Finally, low doses of marizomib and pomalidomide overcomes the cytoprotective effects of MM-host bone marrow microenvironment. Conclusions: Our study provides the preclinical rationale for a clinical protocol evaluating pomalidomide together with marizomib to potentially improve patient outcome in MM.
The hepatoprotective cytokine Cardiotrophin-1 (CT-1) attenuates inflammation and prevents the systemic effects of endotoxemia by promoting M2 macrophage polarization
Authors: J.M. Vélez-Qrtiz, E.S. María, E. Larequi, P. Colodrero, M. Reboredo, J. Muntané, F.J. Padillo, J. Prieto, S. Hervás-Stubb, M. Bustos
Journal: Journal of Hepatology (2017)
A novel farnesoid X receptor agonist: EDP-305, reduces fibrosis progression in animal models of fibrosis
Authors: D.J. Erstad, C.T. Farrar, R. Masia, D.D.S. Ferreira, L. Wei, J.-K. Choi, S. Ghoshal, N. Rotile, Y. Li, M. Chau, K.K. Tanabe, Y.S. Or, P. Caravan, L.-J. Jiang, B.C. Fuchs
Journal: Journal of Hepatology (2017)
T-tubule remodelling disturbs localized β2-adrenergic signalling in rat ventricular myocytes during the progression of heart failure
Authors: Sophie Schobesberger, Peter Wright, Sergiy Tokar, Anamika Bhargava, Catherine Mansfield, Alexey V. Glukhov, Claire Poulet, Andrey Buzuk, Aron Monszpart, Markus Sikkel, Sian E. Harding, Viacheslav O. Nikolaev, Alexander R. Lyon, Julia Gorelik
Journal: Cardiovascular Research (2017)

Cardiomyocyte β2-adrenergic receptor (β2AR) cyclic adenosine monophosphate (cAMP) signalling is regulated by the receptors' subcellular location within transverse tubules (T-tubules), via interaction with structural and regulatory proteins, which form a signalosome. In chronic heart failure (HF), β2ARs redistribute from T-tubules to the cell surface, which disrupts functional signalosomes and leads to diffuse cAMP signalling. However, the functional consequences of structural changes upon β2AR-cAMP signalling during progression from hypertrophy to advanced HF are unknown.Rat left ventricular myocytes were isolated at 4-, 8-, and 16-week post-myocardial infarction (MI), β2ARs were stimulated either via whole-cell perfusion or locally through the nanopipette of the scanning ion conductance microscope. cAMP release was measured via a Förster Resonance Energy Transfer-based sensor Epac2-camps. Confocal imaging of di-8-ANNEPS-stained cells and immunoblotting were used to determine structural alterations. At 4-week post-MI, T-tubule regularity, density and junctophilin-2 (JPH2) expression were significantly decreased. The amplitude of local β2AR-mediated cAMP in T-tubules was reduced and cAMP diffused throughout the cytosol instead of being locally confined. This was accompanied by partial caveolin-3 (Cav-3) dissociation from the membrane. At 8-week post-MI, the β2AR-mediated cAMP response was observed at the T-tubules and the sarcolemma (crest). Finally, at 16-week post-MI, the whole cell β2AR-mediated cAMP signal was depressed due to adenylate cyclase dysfunction, while overall Cav-3 levels were significantly increased and a substantial portion of Cav-3 dissociated into the cytosol. Overexpression of JPH2 in failing cells in vitro or AAV9.SERCA2a gene therapy in vivo did not improve β2AR-mediated signal compartmentation or reduce cAMP diffusion.Although changes in T-tubule structure and β2AR-mediated cAMP signalling are significant even at 4-week post-MI, progression to the HF phenotype is not linear. At 8-week post-MI the loss of β2AR-mediated cAMP is temporarily reversed. Complete disorganization of β2AR-mediated cAMP signalling due to changes in functional receptor localization and cellular structure occurs at 16-week post-MI.
Individuation of presence and combination of genetic risk factors may help to refine the risk for most severe forms of NAFLD
Authors: U. Vespasiani-Gentilucci, C. Dell’Unto, F. Vorini, M.D. Monache, R. Cecere, C. Francia, F. Cerini, G. Galati, P. Gallo, A. De Vincentis, A.M. Pellicelli, A. Baiocchini, A. Picardi
Journal: Journal of Hepatology (2017)
Characterization of novel GT-1b resistant-associated substitutions (RASs) selected by NS5A inhibitor-based regimens
Authors: S. Fourati, F. Donati, A. Soulier, C. Hézode, L. Poiteau, L. Ollier, H. Danso, A. Ahmed-Belkacem, S. Chevaliez, J.-M. Pawlotsky
Journal: Journal of Hepatology (2017)
Mutations in TP53 Gene Is Independent Prognostic Factor for High Grade B-Cell Lymphoma
Authors: Anna Evgenevna Misyurina, Vsevolod Andreevich Misyurin, Andrey Vitalievich Misyurin, Alla Mikhailovna Kovrigina, Sergey Kirillovich Kravchenko, Elena Alexandrovna Baryakh, Aminat Umaraskhabovna Magomedova, Elena Nikolaevna Pushkova, Elena N. Parovichnikova, Valery Grigorievich Savchenko
Journal: Blood (2016)
ReSPECT is a personal emergency care plan summary
Authors: Zoe Fritz, David Pitcher, Claud Regnard, Juliet Spiller, Madeleine Wang
Journal: BMJ (2017)

Advance care plans in the UK vary in style and content, are restricted to specific organisations or localities, and some are many pages long. An effective advance plan to guide immediate decision making in an emergency must be concise, clear, and universally recognised. The recommended summary plan for emergency care and treatment (ReSPECT), which was developed collaboratively by many stakeholders (www.respectprocess.org.uk), aspires …
Phase II study of amrubicin (AMR) for patients (pts) with non-small cell lung cancer (NSCLC) as third-line or fourth-line chemotherapy: Hokkaido Lung Cancer Clinical Study Group trial (HOT) 0901.
Authors: Toshiyuki Harada, Kenichiro Ito, Kei Takamura, Eiki Kikuchi, Satoshi Oizumi, Tomoya Kuda, Shunichi Sugawara, Makoto Maemondo, Yuka Fujita, Ichiro Kinoshita, Akira Inoue, Fumihiro Hommura, Yutaka Katsuura, Hirotoshi Akita, Hiroshi Isobe, Masaharu Nishimura
Journal: Journal of Clinical Oncology (2012)

7571 Background: Although an increasing number of NSCLC pts receive third-line chemotherapy with the established benefit of second-line chemotherapy, the role of cytotoxic agent in this setting has not yet been well defined prospectively. AMR, third-generation synthetic anthracycline agent, has found favorable clinical activity and acceptable toxicity for NSCLC as well as small cell lung cancer. This prospective trial was conducted to evaluate the efficacy and safety of AMR for NSCLC pts as third-line or fourth-line chemotherapy. Methods: Eligible pts had a performance status 0 to 2, failure of second-line or third-line chemotherapy, and adequate organ function. Pts received AMR 35 mg/m 2 intravenously on days 1-3 every 3 weeks. The primary endpoint was disease control rate (DCR: CR + PR + SD). Secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate (CR + PR), and toxicity profile. The estimated accrual was 37 pts to confirm a DCR of 50% as desirable target level and a DCR of 30 % as uninteresting with alpha = 0.05 and beta = 0.20. Results: From August 2009 to May 2011, 41 pts were enrolled from 10 institutions. Patient characteristics were: male/female 29/12; median age 66 (range 43–74); performance status 0/1/2 16/24/1; adenocarcinoma/squamous cell carcinoma/large cell carcinoma/not other specified 30/8/2/1; EGFR mutation positive/negative/unknown 7/26/8; treatment lines 3rd/4th 26/15. The median number of treatment cycles was 2 (range 1-9). The objective responses were CR 0, PR 4, SD 22, PD 14, and NE 1, giving a DCR of 61.0% (95% CI, 46.0-75.9%). Overall response rate was 9.8% (95% CI, 0.6-18.8%). Median PFS was 2.6 months, whereas median survival time was not reached. Grade 3/4 hematological toxicities were neutropenia (68%), anemia (12%), thrombocytopenia (12%), and febrile neutropenia (17%). Grade 3/4 non-hematological toxicities were anorexia (12%), nausea (10%), and pneumonitis (2%). No treatment-related death was observed. Conclusions: AMR shows significant clinical activity with acceptable toxicities as third-line or fourth-line chemotherapyfor advanced NSCLC.
Abstract IA08: Role of the RNA binding protein UNR/CSDE1 in cancer progression
Authors: Fatima Gebauer
Journal: Cancer Research (2017)

Abstract RNA binding proteins (RBPs) are gaining great attention in cancer research for their potential to regulate essentially every hallmark of tumor development. Yet, the molecular mechanisms that underlie these capacities are unclear, particularly in aggressive cancers such as melanoma, where RBPs remain largely uncharacterized. Here we show that the conserved RBP UNR/CSDE1 is over-expressed in melanoma tumors and promotes invasion and metastasis. iCLIP-Seq, RNA-Seq and ribosome profiling combined with in silico studies unveiled sets of pro-metastatic factors coordinately regulated by UNR as part of RNA regulons. In addition to RNA steady state levels, UNR was found to control many of its targets at the level of translation elongation/ termination. Our results identify UNR as an oncogenic modulator of melanoma progression, unravel the underlying molecular mechanisms, and identify potential targets for this therapeutically challenging malignancy. Citation Format: Fatima Gebauer. Role of the RNA binding protein UNR/CSDE1 in cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr IA08.
Serum fibroblast growth factor 19, 7α-Hydroxy-4-Cholesten-3-one, and bile acids and their associations with clinical characteristics in primary sclerosing cholangitis
Authors: C. Levy, M. Shiffman, S. Caldwell, V. Luketic, P. Invernizzi, G. Minuk, P. Pockros, Z. Goodman, D. Ding, A. Billin, B. Mccolgan, S. Djedjos, R. Myers, M. Subramanian, B. Eksteen, C. Bowlus, A. Muir
Journal: Journal of Hepatology (2017)
Directly active antivirals pharmacokinetics in HCV/HIV co-infected patients with advanced hepatic fibrosis
Authors: L. Marinaro, M. Merli, A. Barco, C. Alcantarini, C. Montrucchio, M.C. Tettoni, G. Vendemiati, G. Bocchino, A. De Nicolò, H. Hasson, A. D’Avolio, C.U. Foppa, G. Di Perri, S. Bonora
Journal: Journal of Hepatology (2017)
Collagen proportion area is an independent predictor of longterm outcome in patients with non-alcoholic fatty liver disease
Authors: E. Buzzetti, A. Hall, M. Ekstedt, R. Manuguerra, C. Covelli, M.G. Misas, T.V. Luong, S. Kechagias, E.K. Manesis, M. Pinzani, A.P. Dhillon, E. Tsochatzis
Journal: Journal of Hepatology (2017)
Projected long term impact of elbasvir/grazoprevir compared to sofosbuvir plus pegylated interferon/ribavirin in chronic hepatitis C virus genotype 1 and 4 patients in Italy: translation of the C-EDGE Head-2-Head study findings
Authors: C. Nwankwo, R. Batterson, E. Todd, Y. Jiang, H.L. Platt, Y. Meng
Journal: Journal of Hepatology (2017)
Myeloma Minimal Residual Disease and Surrogacy—Reply
Authors: Nikhil Munshi, Mehmet Kemal Samur, Walter Gregory
Journal: JAMA Oncology (2017)

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Minimal increases of alpha-fetoprotein above the normal value strongly predict HCC development in compensated Caucasian HBV cirrhotics treated by entecavir or tenofovir: a 7-year longitudinal cohort study in 225 patients
Authors: A. Loglio, G. Grossi, M. Iavarone, M. Viganò, A. Sangiovanni, M. Colombo, P. Lampertico
Journal: Journal of Hepatology (2017)
From bench to bedside: The use of the li-Key technology to improve helper peptides for clinical use in cancer vaccines.
Authors: Timothy J Vreeland, Diane F Hale, Alan K. Sears, Guy T. Clifton, Efi Pappou, Raetasha Sheavette Dabney, Alexandros Ardavanis, Ritesh Patil, Sathibalan Ponniah, Eleftheria Anastasopoulou, Sonia A. Perez, Nathan M. Shumway, George Earl Peoples, Elizabeth Ann Mittendorf
Journal: Journal of Clinical Oncology (2012)

2508 Background: Work involving peptide vaccines has shown that peptides containing MHC Class II epitopes, which elicit CD4+ T cell responses, may play a role in potentiating an immune response. The Ii-Key peptide (amino acids 77-80 of the immune-regulatory Ii protein), when covalently linked to an MHC Class II epitope, can induce conformational change in the epitope binding groove, increasing CD4+ T cell stimulation up to 250 fold. Here we present an update of results from clinical trials evaluating this novel technology in an adjuvant breast cancer vaccine targeting HER2/neu. Methods: We reviewed our trials investigating AE37, a hybrid peptide created by the addition of the Ii-Key peptide (LRMK) to AE36 (GVGSPYVSRLLGICL), an MHC Class II-binding peptide from the intracellular domain of the HER2 protein. We have completed a phase I study and are currently conducting a randomized phase II trial of the AE37 peptide + GM-CSF in the adjuvant treatment of disease-free breast cancer patients with any level of HER2 expression (IHC 1-3+ or FISH&gt;1.2). Results: Phase I data showed the vaccine to be safe and effective in raising anti-HER2 immunity. Importantly, even the cohort of patients given AE37 without GM-CSF showed significant increases in both in vivo and in vitro immune responses. To date, we have enrolled 201 patients to our phase II trial (Vaccine (VG)=103, Control (CG)=98). Toxicity has been minimal (99% of local and systemic toxicities grade ≤2). VG patients have shown significant increases in both in vivo and in vitro responses to both AE36 and AE37, with consistently stronger responses to the AE37 hybrid peptide than the native AE36. With a median f/u of 22 months, Kaplan Meier projections estimate recurrence rates of 10.3% in the VG compared to 18% in the CG; a 43% risk reduction. Conclusions: The AE37 peptide vaccine appears to be effective in eliciting a strong immune response and possibly preventing breast cancer recurrence. These results provide an important proof of concept and suggest that additional studies evaluating Ii-Key hybrid peptide vaccines are warranted, whether in the field of immunotherapy or more traditional vaccines.
Brain metastases (BM) development in molecular selected non-small cell lung cancer (NSCLC) patients included in clinical trials
Authors: S. Cedres, N. Pardo, A. Navarro-Mendivil, A. Martinez, A. Martinez de Castro, J. Remon, F. Amair, J. Zeron, M. Vilaro, E. Felip
Journal: Annals of Oncology (2017)
Apoptosis signal-regulating kinase 1 (ASK1) inhibition reduces liver fibrosis and apoptosis in a NLRP3 mutant model of NASH
Authors: S. Schuster, M.D. McGeough, C.D. Johnson, A. Zagorska, G. Budas, H.M. Hoffman, A.E. Feldstein
Journal: Journal of Hepatology (2017)
Combined Effect of Cytotoxic T-lymphocyte antigen 4 (CTLA-4) and Programmed Cell Death 1 Ligand 1 (PD-L1) expression in tumor infiltrating lymphocytes on prognostic outcomes after resection of hepatocellular carcinoma
Authors: J. An, H.J. Kang, J.H. Shim, G.-W. Song, H.C. Lee, D.J. Suh, E. Yu
Journal: Journal of Hepatology (2017)
Motif mimetic of epsin perturbs tumor growth and metastasis
Authors: Yunzhou Dong, Hao Wu, H.N. Ashiqur Rahman, Yanjun Liu, Satish Pasula, Kandice L. Tessneer, Xiaofeng Cai, Xiaolei Liu, Baojun Chang, John McManus, Scott Hahn, Jiali Dong, Megan L. Brophy, Lili Yu, Kai Song, Robert Silasi-Mansat, Debra Saunders, Charity Njoku, Hoogeun Song, Padmaja Mehta-D’Souza, Rheal Towner, Florea Lupu, Rodger P. McEver, Lijun Xia, Derek Boerboom, R. Sathish Srinivasan, Hong Chen
Journal: Journal of Clinical Investigation (2016)

During the assembly of Figure 10B, incorrect flow cytometry panels were inadvertently included for the Tg sm/p22phox + tempol sample.In addition, a different replicate is now provided for the Tg sm/p22phox sample in Figure 10A.The correct figure panels are below.
Recurrent INHBE-GLI1 fusions in hepatocellular adenomas with sonic hedgehog pathway activation
Authors: J.C. Nault, G. Couchy, C. Balabaud, G. Morcrette, S. Caruso, J.-F. Blanc, Y. Bacq, J. Caldéraro, V. Paradis, J. Ramos, V. Gnemmi, N. Sturm, E. Savier, L. Chiche, J. Selves, C. Pilati, A. Laurent, A. DeMuret, B. Lebail, S. Rebouissou, S. Imbeaud, P. Bioulac-Sage, E. Letouze, J. Zucman-Rossi
Journal: Journal of Hepatology (2017)
MOLECULAR REMISSION IN A MULTIPLE MYELOMA PATIENT AFTER A NON MYELOABLATIVE ALLOGENEIC TRANSPLANT: PROOF OF PRINCIPLE
Authors: Benedetto Bruno, Marco Ladetto, Monica Astolfi, S Sametti, Luciana Veneziano, G Aitoro, Luisa Giaccone, Antonio Palumbo, Alessandro Pileri, Mario Boccadoro, R. Storb
Journal: Blood (2001)
The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency
Authors: Sonya Cressman, Stuart J. Peacock, Martin C. Tammemägi, William K. Evans, Natasha B. Leighl, John R. Goffin, Alain Tremblay, Geoffrey Liu, Daria Manos, Paul MacEachern, Rick Bhatia, Serge Puksa, Garth Nicholas, Annette McWilliams, John R. Mayo, John Yee, John C. English, Reka Pataky, Emily McPherson, Sukhinder Atkar-Khattra, Michael R. Johnston, Heidi Schmidt, Frances A. Shepherd, Kam Soghrati, Kayvan Amjadi, Paul Burrowes, Christian Couture, Harmanjatinder S. Sekhon, Kazuhiro Yasufuku, Glenwood Goss, Diana N. Ionescu, David M. Hwang, Simon Martel, Don D. Sin, Wan C. Tan, Stefan Urbanski, Zhaolin Xu, Ming-Sound Tsao, Stephen Lam
Journal: Journal of Thoracic Oncology (2017)

IntroductionLung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited.MethodsParticipants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk–selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency.ResultsUse of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non–lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention.ConclusionsNon–lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise.