tbuckley/cabot-search huggingface dataset:
Abstract P304: Salvianolic Acid B Suppresses Human Monocyte-Derived Dendritic Cell Maturation via PPARγ Activation
Authors: Aijun Sun, Hongying Liu, Shijun Wang, Dazhuo Shi, Lei Xu, Yong Cheng, Keqiang Wang, Keji Chen, Yunzeng Zou, Gunbo Ge
Journal: Circulation Research (2011)

Background and purpose: Salvianolic acid B (Sal B), a water-soluble antioxidant derived from a medicinal herb, is known to be effective in the prevention of atherosclerosis. Here, we tested the hypothesis that the anti-atherosclerotic effect of Sal B might be mediated by suppressing human monocyte-derived dendritic cells (DCs) maturation. Experimental approach: DCs was derived by incubating purified human monocytes with GM-CSF and IL-4. DCs was pre-incubated with or without Sal B and stimulated by oxidized low density lipoprotein (ox-LDL) in the presence or absence of PPAR-γ siRNA. Expression of DCs membrane molecules were analyzed by FACS, cytokines were measured by ELISA, and TLR4 associated signaling pathway was determined by Western blotting. Key results: Ox-LDL promoted DCs maturation, stimulated CD40, CD86, CD1a, HLA-DR expression and IL-12, IL-10, TNF-α production and upregulated TLR4 signaling. These effects could be significantly inhibited by Sal B. Sal B also triggered PPAR-γ activation and promoted PPAR-γ nuclear translocation, attenuated ox-LDL-induced upregulation of TLR4 and myeloid differentiation primary-response protein 88 (MyD88), and inhibited downstream p38-MAPK signaling cascade. Knocking down PPAR-γ through siRNA transfection significantly blocked above mentioned effects of Sal B. Conclusions and implications: Our data suggested that Sal B effectively suppressed ox-LDL-induced DCs maturation through PPAR-γ activation.
Fludarabine/Busulfan Plus Low Dose TBI As Reduced Intensity Conditioning in Older Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Myeloid Malignancies
Authors: Manar Mohamed Ibrahim Khalil, Hans A. Messner, Jeffrey H. Lipton, Dennis Dong Hwan Kim, Auro Viswabandya, Santhosh Thyagu, Uday Deotare, Fotios V. Michelis
Journal: Blood (2016)
Hepatocyte nanodelivery using siRNA c-Jun N-terminal Kinase-2 (siJnk2) for the treatment of chronic liver disease
Authors: M.M. Woitok, D. Doleschel, M.E. Zoubek, F. Kiessling, W. Lederle, C. Trautwein, F.J. Cubero
Journal: Journal of Hepatology (2017)
Is the high cost of CML care "worth it"?
Authors: Pei-Jung Lin, Aaron Winn, Susan Kenyon Parsons, Peter J Neumann, Elisa S Weiss, Joshua T Cohen
Journal: Journal of Clinical Oncology (2015)

e17801 Background: The high prices of chronic myeloid leukemia (CML) therapy are well recognized, but less discussion has focused on the value of health care spending on the disease. This study examined whether the added costs have been “worth” the benefits in U.S. CML patients. Methods: We analyzed trends in CML cost and survival over time of 8,510 patients using real-world data from the 1994-2009 Surveillance, Epidemiology and End Results (SEER)-Medicare linked database and the Truven Health MarketScan database. We estimated life expectancy over a 15-year duration post-diagnosis using Weibull survival modeling and projected the corresponding costs using generalized linear modeling, adjusting for patient characteristics. We estimated population-level survival, health care costs, and incremental cost-effectiveness ratios (ICERs, expressed as cost per life year [LY] gained) separately for patients over 65 (“older”), 65 and under (“younger”), and both populations combined. Results: We found that therapeutic improvements in the treatment of CML have been associated with survival gains between 1995 and 2007. During the same timeframe, CML costs have decreased among younger patients and increased for older patients. The ICERs were cost-saving for younger patients, $105,000/LY for older patients, and $29,000/LY at the aggregate level for both populations combined. Conclusions: Our study is the first to our knowledge to examine the value of CML care in the U.S. since the emergence of effective new therapies. Our findings showed that, despite high costs, CML care provided good value for money. Treatment for CML was cost-effective for the population as a whole and cost-saving among younger patients. Our study sheds light on the value of health care spending on CML by considering both the costs and the benefits.
Prospective validation of the Enhanced Liver Fibrosis test for the prediction of disease progression in a randomized trial of patients with primary sclerosing cholangitis
Authors: C. Bowlus, K. Patel, G. Hirschfield, I. Guha, R. Chapman, O. Chazouilleres, D. Ding, C. Jia, B. Mccolgan, R. Myers, M. Subramanian, J. McHutchison, A. Muir, Z. Goodman, W. Rosenberg, C. Levy
Journal: Journal of Hepatology (2017)
Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch
Authors: Jarkko Salojärvi, Olli-Pekka Smolander, Kaisa Nieminen, Sitaram Rajaraman, Omid Safronov, Pezhman Safdari, Airi Lamminmäki, Juha Immanen, Tianying Lan, Jaakko Tanskanen, Pasi Rastas, Ali Amiryousefi, Balamuralikrishna Jayaprakash, Juhana I Kammonen, Risto Hagqvist, Gugan Eswaran, Viivi Helena Ahonen, Juan Alonso Serra, Fred O Asiegbu, Juan de Dios Barajas-Lopez, Daniel Blande, Olga Blokhina, Tiina Blomster, Suvi Broholm, Mikael Brosché, Fuqiang Cui, Chris Dardick, Sanna E Ehonen, Paula Elomaa, Sacha Escamez, Kurt V Fagerstedt, Hiroaki Fujii, Adrien Gauthier, Peter J Gollan, Pauliina Halimaa, Pekka I Heino, Kristiina Himanen, Courtney Hollender, Saijaliisa Kangasjärvi, Leila Kauppinen, Colin T Kelleher, Sari Kontunen-Soppela, J Patrik Koskinen, Andriy Kovalchuk, Sirpa O Kärenlampi, Anna K Kärkönen, Kean-Jin Lim, Johanna Leppälä, Lee Macpherson, Juha Mikola, Katriina Mouhu, Ari Pekka Mähönen, Ülo Niinemets, Elina Oksanen, Kirk Overmyer, E Tapio Palva, Leila Pazouki, Ville Pennanen, Tuula Puhakainen, Péter Poczai, Boy J H M Possen, Matleena Punkkinen, Moona M Rahikainen, Matti Rousi, Raili Ruonala, Christiaan van der Schoot, Alexey Shapiguzov, Maija Sierla, Timo P Sipilä, Suvi Sutela, Teemu H Teeri, Arja I Tervahauta, Aleksia Vaattovaara, Jorma Vahala, Lidia Vetchinnikova, Annikki Welling, Michael Wrzaczek, Enjun Xu, Lars G Paulin, Alan H Schulman, Martin Lascoux, Victor A Albert, Petri Auvinen, Ykä Helariutta, Jaakko Kangasjärvi
Journal: Nature Genetics (2017)

Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.
Abstract 53: PTEN Nuclear Export and p53 Inhibition Mediate Free Fatty Acid-Induced Oxidative Stress in Endothelial Cells
Authors: Yong Wu, Hongci Zhou, Xuan Liu
Journal: Circulation Research (2012)

Oxidative stress induced by free fatty acids (FFA) contributes to metabolic syndrome-associated development of cardiovascular diseases. In this study, we investigated the mechanisms involved in the p53-mediated regulation of antioxidant enzyme glutathione peroxidase-1 (GPx-1) expression and induction of intracellular ROS levels by palmitic acid (PA). The p53 pathway plays a very important role in regulating ROS production. We exposed human umbilical vein endothelial cells (HUVEC) to PA and demonstrated that p53 acetylation and protein levels decrease in a dose-dependent manner. The p53 downregulation correlated with a decrease in its downstream target GPx-1 and increase in the production of intracellular ROS. Nuclear PTEN was previously identified as an important factor involved in the upregulation of p53 acetylation, transcription activity and protein stability. Here, we show treatment of HUVEC with PA induced increase in PTEN phosphorylation at Ser380 and in interaction between PTEN and HAUSP, a deubiquitylating enzyme that cleaves ubiquitin from its substrates. The increased PTEN-HAUSP interaction leads to a dramatic decrease in PTEN mono-ubiquitination and increase in PTEN nuclear export, which prevents p53 acetylation. Pharmacologic inhibition or genetic ablation of mammalian target of rapamycin (mTOR) or S6K abolished PA-induced PTEN phosphorylation, PTEN-HAUSP interaction and PTEN nuclear export, suggesting that mTOR/S6K pathway is responsible for nuclear PTEN phosphorylation. Importantly, inhibition of mTOR/S6K pathway significantly blocks PA-induced PTEN nuclear export, p53-mediated GPx-1 expression, and increase in ROS production in HUVEC cells. These results demonstrate that PA treatment elevates PTEN-Ser380 phosphorylation through mTOR/S6K pathway. Once phosphorylated, PTEN in turn binds to HAUSP, reduces its mono-ubiquitination and nuclear localization, which prevents p53 from activating GPx-1 to compromise the most important antioxidant defense system and cause oxidative damage to human vascular endothelium.
Costimulatory effect of agonistic 4-1BB antibody on proliferation and effector phenotype of tumor-infiltrating lymphocytes in melanoma.
Authors: Amod Sarnaik, Anthony Bilotto, Maria Jure-Kunkel, MacLean S Hall, Wenshi Wang, Ibrahim Younos, Shari Pilon-Thomas, Jeffrey S. Weber
Journal: Journal of Clinical Oncology (2012)

2511 Background: Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) is a promising form of immunotherapy with a 20-30% durable response rate. Its widespread implementation is limited by the relatively long time needed to establish TIL in vitro and the lack of effective tumor reactivity. Our objective was to incorporate co-stimulation with 4-1BB agonism to optimize TIL growth preparation time and tumor reactivity to improve outcomes. Methods: 7 metastatic melanoma patients were consented to an IRB-approved tissue procurement protocol. For each specimen, TIL were propagated in vitro from 4 melanoma tumor fragments per condition with standard 6000 IU/mL of IL-2 and either 10 ug/mL of 4-1BB agonistic antibody (BMS-663513) or its isotype control. After 3 weeks, TIL were counted and phenotyped using flow cytometry. TIL were re-stimulated with HLA-matched melanomas and assessed for interferon-γ (IFNγ) release by ELISA. Statistical comparisons involved the 2-tailed, paired t test using GraphPad Prism software. Results: 4-1BB treatment yielded a median 4.3x10 7 TIL (range 1.1x10 7 -8.4x10 7 ) compared to a median 2.3x10 7 cells in the control (range 1.5x10 6 -5.3x10 7 , p = 0.009). This is clinically significant as the initial minimum target number for TIL generation is 3x10 7 . On phenotypic analysis compared to control, 4-1BB treatment resulted in a 1.5X higher CD8 + cell numbers (p=0.02), a 6X lower CD4 + cell numbers (p=0.02), and 5.5X lower CD4 + CD25 + FoxP3 + Treg cell numbers (p=0.09). A paired sample was re-stimulated in triplicate with HLA-matched tumor target, and ELISA of the supernatant treated with 4-1BB yielded 1.6 fold higher IFNγ (p=0.05). A paired sample was then assayed for known markers of T cell cytolytic activity: EOMES and perforin. 4-1BB treatment resulted in 34.5% EOMES and perforin double positive TIL compared to 18.8% in the control group. Conclusions: 4-1BB agonism is associated with enhanced kinetics of TIL proliferation, increased yield of CD8 + TIL, lower Treg numbers, increased markers of cytolysis, and enhanced IFNγ release upon tumor re-stimulation. 4-1BB agonism may be a useful adjuvant in the generation of TIL in future clinical trials.
Abstract B14: Evidence that Tma20 and Tma22 do not promote translation re-initiation in yeast
Authors: Victoria Torrance, David Lydall
Journal: Cancer Research (2017)

Abstract Translation Machinery Association 20 (Tma20) and Tma22 are two conserved proteins which form a complex involved in translation initiation. The human homolog of TMA20 is an oncogene, originally identified in a T-cell lymphoma and has been shown to induce cell proliferation. Tma20 and Tma22 homologs in Drosophila have been shown to promote translation of mRNAs which contain uORFs by promoting translation re-initiation. uORFs serve as major regulators of gene expression, repressing translation. In yeast Tma20 and Tma22 have recently been shown to have a role in telomere biology by decreasing fitness of cells with uncapped telomeres. To understand how Tma20 and Tma22 affect growth of cells with uncapped telomeres we have investigated translation re-initiation in yeast using new luciferase reporter constructs. Using transcript leader sequences from 22 genes we showed that, as expected, the majority of uORFs repressed expression but found no evidence to suggest that Tma20 or Tma22 promote translation re-initiation in 21 of these genes. However our data suggests that Tma20 and Tma22 inhibit translation re-initiation of the remaining gene, BRE4. Our data suggests that the function of Tma20 and Tma22 is not conserved from Drosophila to yeast. Our finding that Tma20 and Tma22 inhibit translation re-initiation on BRE4 is in agreement with studies in mammalian cells which have shown that Tma20 and Tma22 promote the dissociation of 40S ribosomal subunit from mRNA following translation termination. Our data suggests that perhaps the human homologs of Tma20 and Tma22 may not promote translation re-initiation as has previously been assumed. Citation Format: Victoria Torrance, David Lydall. Evidence that Tma20 and Tma22 do not promote translation re-initiation in yeast. [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 B14.
EML4-ALK rearrangement detection in malignant pleural effusions from patients with advanced non-small cell lung cancer: Feasibility and predictive value.
Authors: Jia Zhong, Jie Wang, Hua Bai
Journal: Journal of Clinical Oncology (2015)

e19094 Background: To evaluate the feasibility of pleural effusions as surrogate samples for the detection of echinoderm microtubule-associated proteinlike4 (EML4)-anaplastic lymphoma kinase (ALK), and to investigate the prognostic and predictive value of EML4-ALK in pleural effusions of non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed 109 NSCLC patients with malignant pleural effusion (MPE). EML4-ALK was identified using paraffin embedded tumor cells in pleural effusion samples by immunohistochemistry (Ventana). EGFR mutation was determined by cell-free DNA in MPE, using cell denaturing high-performance liquid chromatography (DHPLC). Results: 5 of 109 (4.58%) were identified as EML4-ALK cases using paraffin embedded tumor cells in MPE; EML4-ALK cases were detected in 5/61(8.20%) patients of the EGFR wild type subgroup. Patients with an EML4-ALK rearrangement were more likely to be of the EGFR wild type subgroup (5/5, P =0.043). The concordance of EML4-ALK and EGFR mutation in pleural effusions and in biopsy/surgical tissue was 88.9% and 83.3%, respectively. For patients with EML4-ALK rearrangement in MPE, the progression free survival (PFS) was inferior when compared to patients with EGFR mutation, and similar to the EGFR/ALK double negative groups for treatment with EGFR-TKI (1.00 vs. 8.27 vs. 3.03months, P= 0.009). However, PFS appeared to be prolonged in chemotherapy (9.27 vs. 6.53 vs. 3.33 months, P= 0.095) as compared to the other two groups. Moreover, patients with EML4-ALK in MPE benefited from crizotinib treatment. Conclusions: EML4-ALK rearrangement detection in malignant pleural effusions can be used as a complementary method for EML4-ALK detection. Gene mutations in pleural effusions have predictive value for treatment.
Autologous liver transplantation in end-stage hepatic alveolar echinoccossis with 51 patients’ experience–where do we stand?
Authors: T. Aji, J.-H. Dong, Y.-M. Shao, J.-M. Zhao, T. Li, P. Shalayiadang, B. Ran, T.-M. Jiang, T. Tuxun, R.-Q. Zhang, Y.-B. He, H. Wen, J.-F. Huang
Journal: Journal of Hepatology (2017)
HEV as a cause of acute hepatitis acquired in Switzerland
Authors: M.F. Christinet, C. Doerig, H. Moulin, F. Bihl, F. Brunner, B. Müllhaupt, D. Semela, F. Stickel, B.T. Beretta-Piccoli, V. Aubert, A. Telenti, G. Greub, R. Sahli, D. Moradpour
Journal: Journal of Hepatology (2017)
Psoriasis and comorbid diseases
Authors: Junko Takeshita, Sungat Grewal, Sinéad M. Langan, Nehal N. Mehta, Alexis Ogdie, Abby S. Van Voorhees, Joel M. Gelfand
Journal: Journal of the American Academy of Dermatology (2017)

Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being recognized as a systemic inflammatory disorder. Psoriatic arthritis is a well-known comorbidity of psoriasis. A rapidly expanding body of literature in various populations and settings supports additional associations between psoriasis and cardiometabolic diseases, gastrointestinal diseases, kidney disease, malignancy, infection, and mood disorders. The pathogenesis of comorbid disease in patients with psoriasis remains unknown; however, shared inflammatory pathways, cellular mediators, genetic susceptibility, and common risk factors are hypothesized to be contributing elements. As additional psoriasis comorbidities continue to emerge, education of health care providers is essential to ensuring comprehensive medical care for patients with psoriasis.
Different Pediatric Survival After Cardiac Arrest—Reply
Authors: Farhan Bhanji, Amy H. Praestgaard, Alexis A. Topjian
Journal: JAMA Pediatrics (2017)

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Degree of liver fibrosis regression predicted by transient elastography after cure of chronic hepatitis C with direct acting antivirals is overestimated but confirmed by liver biopsy
Authors: P. Pockros, A.M. Crissien-Martinez, C. Frenette, C. Skillin, F. Bao, E. Du, J.J. Pan, J. Waalen
Journal: Journal of Hepatology (2017)
EXalt3: A phase III study of ensartinib (X-396) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)
Authors: L. Horn, Y.-L. Wu, M. Reck, C. Liang, F. Tan, K. Harrow, V. Oertel, G. Dukart, T.S.K. Mok
Journal: Annals of Oncology (2017)
Effect of Combined Patient Decision Aid and Patient Navigation vs Usual Care for Colorectal Cancer Screening in a Vulnerable Patient Population
Authors: Daniel S. Reuland, Alison T. Brenner, Richard Hoffman, Andrew McWilliams, Robert L. Rhyne, Christina Getrich, Hazel Tapp, Mark A. Weaver, Danelle Callan, Laura Cubillos, Brisa Urquieta de Hernandez, Michael P. Pignone
Journal: JAMA Internal Medicine (2017)

Colorectal cancer (CRC) screening is underused, especially among vulnerable populations. Decision aids and patient navigation are potentially complementary interventions for improving CRC screening rates, but their combined effect on screening completion is unknown.
Liver progenitors and hematopoietic stem cells in acute liver failure and cirrhosis
Authors: E. Solanas, F.J. Aranguren, A. Lue, S. Lorente, J.A. Moreno, J. Medrano, A. Gonzales, J.C. Segovia, M.A. De Gregorio, M.J. Morandeira, M.T. Serrano
Journal: Journal of Hepatology (2017)
Repair macrophages in acute liver failure
Authors: Tobias Puengel, Frank Tacke
Journal: Gut (2017)

Inflammation is increasingly recognised to critically determine the clinical course and outcome of acute liver failure (ALF). On the one hand, massive hepatocyte cell death triggers immune cell activation and recruitment to the liver, which can stimulate immune-mediated liver damage. On the other hand, systemic activation of inflammation, systemic inflammatory response syndrome, promotes multiple organ failure and defective antimicrobial responses.1 Innate immune mechanisms play a prominent role in ALF. Mouse models of acute liver injury revealed that liver-resident macrophages, Kupffer cells, sense hepatocyte-mediated release of alarmins, which results in Kupffer cell activation and cytokine release.2 Hence, neutrophils and monocytes are recruited from the bloodstream to the site of injury. During the early phase after recruitment, neutrophils and monocytes have an inflammatory phenotype and aggravate tissue damage.3 4 However, there is ample experimental evidence that monocyte-derived macrophages change their phenotype in the liver, if injury has terminated, towards repair-promoting phagocytes.5 6 Up to now, the ‘human counterpart’ of inflammatory versus restorative macrophages in ALF has been vague. In this issue of Gut , Dr. Antoniades and coworkers present compelling experimental evidence from human samples and a mouse model that restorative macrophages in ALF …