tbuckley/cabot-search huggingface dataset:
Bayesian Inference of Evolutionary Histories under Time-Dependent Substitution Rates
Authors: Jade Vincent Membrebe, Marc A Suchard, Andrew Rambaut, Guy Baele, Philippe Lemey
Journal: Molecular Biology and Evolution (2019)

Many factors complicate the estimation of time scales for phylogenetic histories, requiring increasingly complex evolutionary models and inference procedures. The widespread application of molecular clock dating has led to the insight that evolutionary rate estimates may vary with the time frame of measurement. This is particularly well established for rapidly evolving viruses that can accumulate sequence divergence over years or even months. However, this rapid evolution stands at odds with a relatively high degree of conservation of viruses or endogenous virus elements over much longer time scales. Building on recent insights into time-dependent evolutionary rates, we develop a formal and flexible Bayesian statistical inference approach that accommodates rate variation through time. We evaluate the novel molecular clock model on a foamy virus cospeciation history and a lentivirus evolutionary history and compare the performance to other molecular clock models. For both virus examples, we estimate a similarly strong time-dependent effect that implies rates varying over four orders of magnitude. The application of an analogous codon substitution model does not implicate long-term purifying selection as the cause of this effect. However, selection does appear to affect divergence time estimates for the less deep evolutionary history of the Ebolavirus genus. Finally, we explore the application of our approach on woolly mammoth ancient DNA data, which shows a much weaker, but still important, time-dependent rate effect that has a noticeable impact on node age estimates. Future developments aimed at incorporating more complex evolutionary processes will further add to the broad applicability of our approach.
SAT-376-Bile acids induce STAT3 and repress FOXP3 expression in hepatic CD4 lymphocytes under cholestatic conditions
Authors: Ramesh Kudira, Celine Silva-Lages, Amy Taylor, Tiffany Shi, Rebekah Karns, Mary Mulen, Wujuan Zhang, Kenneth Setchell, Alexander Miethke
Journal: Journal of Hepatology (2019)
Abstract 14984: Healthy Eating Healthy Aging: a Community-based Intervention Program for Older Adult Asian American, Native Hawaiian and Pacific Islanders
Authors: Eun Jeong Lee, Linda K Ko, Annie Feng, Cindy Tang, Cevadne Lee
Journal: Circulation (2017)

Background: Cardiovascular disease is the 2nd leading cause of death for Asian Americans, Native Hawaiians & Pacific Islanders (AANHPIs) between the ages 65-84, the 1st leading cause of death among...
SAT-133-2D-Shear-Wave elastography predicts survival in advanced chronic liver disease
Authors: Jonel Trebicka, Victor De Ledinghen, Christophe Aubé, Aleksander Krag, Laurent Castera, Jérôme Dumortier, Jerome Boursier, Mireen Friedrich-Rust, Pol Stanislas, Ivica Grgurevic, Rongqin Zheng, Sven Francque, Halima Gottfriedova, Ioan Sporea, Annalisa Berzigotti, Wenping Wang, Pierre-Emmanuel Rautou, Filipe Andrade, Christian P Strassburg, Jian Zheng, Christophe Cassinotto, Merrouche Wassil, Ditlev Rasmussen, Valérie Vilgrain, Aymeric Guibal, Camille Vassord, Stefan Zeuzem, Luisa Vonghia, Renata Senkerikova, Alina Popescu, Anita Paisant, Cristina Margini, Floraine Zuberbulher, Marie Irles-Depe, Maja Thiele, Christian Jansen
Journal: Journal of Hepatology (2019)
Capping Silica Nanoparticles with Tryptophan‐Mediated Cucurbit[8]uril Complex for Targeted Intracellular Drug Delivery Triggered by Tumor‐Overexpressed IDO1 Enzyme
Authors: Haishi Qiao, Jing Jia, Haowen Shen, Sibo Zhao, Enping Chen, Wei Chen, Bin Di, Chi Hu
Journal: Advanced Healthcare Materials (2019)

Abstract Nanosystems responsive to tumor‐specific enzymes are considered as a highly attractive approach to intracellular drug release for targeted cancer therapy. Mesoporous silica nanoparticles are capped with tryptophan‐mediated cucurbit[8]uril complex with Fe 3 O 4 to minimize the premature drug leakage while being able to deliver the payload on demand at the target tissue. The supramolecular interaction between tryptophan and cucurbit[8]uril is disrupted in the presence of indoleamine 2,3‐dioxygenase 1 (IDO1) enzyme (abundant in the tumor intracellular microenvironment), which catalyzes the metabolism of tryptophan into N ‐formylkynurenine, resulting in the disassembly of the “gate‐keeper” of the nanocarriers and intracellular release of therapeutics exclusively in tumor cells. The drug release from the nanocarrier with high selectivity to overexpressed IDO1 enzyme induces significant cytotoxicity against HepG2 cells in vitro, as well as the superior antitumor effects in vivo. This robust supramolecular nanosystem with sophisticated structure and property provides a promising platform for intracellular drug release targeting the intrinsic microenvironmental enzyme inside the tumor cells.
SAT-282-Decrease in HbA1c accounts for the rapid decline in the measurement of liver stiffness by transient elastography in diabetic patients
Authors: Tugba Celebi, Nilay Danis, Fulya Gunsar, Galip Ersoz, Zeki Karasu, Ilker Turan, Omer Ozutemiz, Ulus Akarca
Journal: Journal of Hepatology (2019)
THU-340-Epidemiology of NAFLD and advanced fibrosis in the French general population: A population-based cohort study in 118, 664 subjects (NASH-CO study)
Authors: Lawrence Serfaty, Oumarou Nabi, Jerome Boursier, Philippe Mathurin, Victor De Ledinghen, Marcel Goldberg, Marie Zins, Karine Lacombe
Journal: Journal of Hepatology (2019)
SAT-223-AA genotype of the deSNP rs6726639 of gene MERTK (MER Tyrosine Kinase) is associated with development of hepatocellular carcinoma after hepatitis C virus clearance
Authors: Vincenza Calvaruso, Stefania Grimaudo, Salvatore Petta, Rosaria Maria Pipitone, Giuseppe Cabibbo, Elisabetta Conte, Bianca Magro, Francesca Rini, Ciro Celsa, Lorenza Di Marco, Calogero Camma, Antonio Craxi, Vito Di Marco
Journal: Journal of Hepatology (2019)
Anti-proliferative activity of bromodomain inhibitors JQ1 and OTX015 in triple negative breast cancer.
Authors: Alberto Ocana, Veronica Corrales-Sanchez, Javier Perez Peña, Gemma Serrano-Heras, Maria Jose Gascon-Escribano, Juan Carlos Montero, Atanasio Pandiella
Journal: Journal of Clinical Oncology (2015)

e12078 Background: Triple negative breast cancer is a devastating disease with limited therapeutic options beyond standard chemotherapy. BET bromodomain inhibitors are a new family of compounds that reduce activity of oncogenic transcription factors through the inhibition of bromodomains. In the present study we explore the effect of bromodomain inhibitors JQ1 and OTX015 on triple negative cancer cells. Methods: We used a panel of triple negative breast cancer cell lines including HS578T, BT549, MDAMB231 and HCC3153. Cell proliferation and growth was measured by MTT uptake and 3D growth in matrigel. Evaluation of apoptosis and cell cycle was performed by flow cytometry using Annexin V and propidium iodide, respectively. Western-blots were used for evaluation of protein expression. To evaluate if JQ1 combined with other chemotherapy drugs was synergistic, additive, or antagonist, we used the CalcuSyn v2.0 software program. Results: Doses of JQ1 and OTX015 in the nanomolar ranged reduced proliferation and cell growth in triple negative cell lines including HS578T, BT549, MDAMB231 and HCC3153. Treatment with JQ1 at 200nM and 500nM led to arrest at the G0/G1 phase in HS578T and MDAMB231 at 12 and 24 hours; that was confirmed by the biochemical evaluation of cell cycle mediators. An induction of apoptosis was observed at 48 hours in HS578T. Administration of JQ1 with chemotherapies showed synergistic effects with taxanes and vinca-alkaloids in HS578. Effect on bromodomain proteins and downstream effectors will be presented at the meeting. Conclusions: BET bromodomain inhibitors JQ1 and OTX015 show antiproliferative effects in a panel of triple negative breast cancer cell lines. JQ1 induces an arrest at G0/G1 and synergizes with some chemotherapies. Further insights into the mechanism of action will be presented at the meeting.
Detection of EGFR activating and T790M resistance mutations in plasma of lung cancer patients using combined exosomal RNA and cfDNA capture.
Authors: Kay Brinkmann, Daniel Enderle, Alexandra Spiel, Tina Koestler, Jennifer Emenegger, Johan Skog, Mikkel Noerholm, Vincent J. O'Neill
Journal: Journal of Clinical Oncology (2015)

e22156 Background: Initial response to tyrosine kinase inhibitors (TKIs) in NSCLC patients with EGFR activating mutations are commonly observed, however patients inevitably progress as a consequence of acquired resistance (AR). Secondary mutations in the EGFR domains play a role in clinical resistance of a substantial portion of patients, and novel agents are in development in this setting. Tissue based assays, requiring repeat biopsy, are less attractive, and detection of AR mutations in circulation would be an appealing alternative. Here we present data demonstrating the feasibility of detection of activating and AR EGFR mutations using a combined single-step exosomal RNA (exoRNA) and cfDNA approach to maximize sensitivity. Methods: We applied our proprietary column-based method to co-isolate both exoRNA and cfDNA from 21 plasma samples (2 mL each) of lung cancer patients collected at the time of clinical resistance to EGFR TKI therapy, which were EGFR-genotyped on time-matched tissue from a repeat biopsy. The resulting plasma total nucleic acids were subjected to reverse transcription and subsequent mutation analysis by targeted next generation sequencing (NGS) of select genes. We analyzed a disease-specific gene panel covering 9 mutation hotspots from 6 genes including EGFR mutations on exon 19, 20 and 21 in a qualitative and quantitative manner. NGS data was generated using a custom library preparation method and bioinformatics pipeline to efficiently call the rare mutations. Results: Our data demonstrate the ability to detect activating and AR mutations on exoRNA and cfDNA co-isolated from plasma of lung cancer patients. Concordance with tissue (shown below) was 17/21 (81%) for activating mutations; and 12/16 (75%) for AR mutations. Additionally, we demonstrate that all T790M-positive patients also exhibit activating EGFR mutations on exon 19 and/or exon 21. Conclusions: Detection of both activating and AR mutations to EGFR therapy in plasma is feasible and offers a highly sensitive alternate to repeat biopsy. Positive Agreement with Tissue Sensitizing EGFR mutations T790M mutation All stages 81% (17/21) 75% (12/16) M0/M1a 67% (4/6) 40% (2/5) M1b 87% (13/15) 82% (9/11)
A surface-engineered polyetheretherketone biomaterial implant with direct and immunoregulatory antibacterial activity against methicillin-resistant Staphylococcus aureus
Authors: Wei Liu, Jinhua Li, Mengqi Cheng, Qiaojie Wang, Yebin Qian, Kelvin W.K. Yeung, Paul K. Chu, Xianlong Zhang
Journal: Biomaterials (2019)
Variations in Modeling for Treating All Patients With Stroke With Suspected Large Vessel Occlusion
Authors: Willemijn J. Maas, Maarten Uyttenboogaart, Maarten M. H. Lahr
Journal: JAMA Neurology (2019)

To the Editor We read the article by Holodinsky et al,1 who reported the results of a modeling study to identify the optimal triage and transport strategy for patients suspected of having large-vessel occlusion, with interest.
THU-131-Effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir for retreatment of chronic hepatitis C patients with a previous failure to direct-acting antivirals: A real-life study from the NAVIGATORE Lombardia and Veneto Networks
Authors: Elisabetta Degasperi, Angiola Spinetti, Andrea Lombardi, Simona Landonio, Pier Giorgio Scotton, Luisa Pasulo, Antonio Carlotto, Alessia Giorgini, Pietro Pozzoni, Paolo Angeli, Maurizio Carrara, Massimo Puoti, Federico Gatti, Giada Carolo, Maria Vinci, Alessia Zoncada, Paolo Bonfanti, Alessio Aghemo, Alessandro Soria, Riccardo Centenaro, Franco Maggiolo, Francesco Paolo Russo, Pierangelo Rovere, Sara Piovesan, Franco Capra, Filippo Viviani, Lorenzo Morini, Roberta Soffredini, Canio Carriero, Stefania Paolucci, Franco Noventa, Alfredo Alberti, Pietro Lampertico, Stefano Fagiuoli
Journal: Journal of Hepatology (2019)
THU-311-Liver enzymes cut offs in patients with advanced non-alcoholic fatty liver disease: A multi-center study
Authors: Ma Ai Thanda Han, Rola Saouaf, Nabil Noureddin, Jonathan Grotts, Vinay Sundaram, Andrea Scott, Mahsa Mansouri, Mary Barbara, Matthew Tjahja, Emmanuel Thomas, Zeid Kayali, Edward Mena, Naim Alkhouri, Mazen Noureddin
Journal: Journal of Hepatology (2019)
Correlation of histopahologic response and prognostic markers with survival in locally advanced non-small cell lung cancer patients who have treated with neoadjuvant chemotherapy.
Authors: Nadire Kucukoztas, Arzu Oguz, Samed Rahatli, Omer Dizdar, Gul Sema Yildiran Keskin, Ozgur Ozyilkan, Ozden Altundag
Journal: Journal of Clinical Oncology (2015)

e18521 Background: We aimed to determine the response and prognosis in patients with stage III NSCLC who had received neoadjuvant therapy and also to determine the relationship with prognosis and treatment response of the expression of ERCC1 and RRM1. Methods: 27 patients with stage III NSCLC were included in this study who received neoadjuvant chemotherapy and had been operated between 2003 and 2013. Lung tissue biopsies were evaluated by immunohistochemical methods for ERCC1 protein expression in patients who received neoadjuvant cisplatin and for RRM1 protein expression in patients who received neoadjuvant gemcitabine. Results: 1 (3.7%) women and 26 (96.3%) male patients were enrolled in the study. Median age was 59 (45-75). 14 patients (51.9%) underwent lobectomy and 13 patients (48.1%) were performed pneumonectomy. 19 patients (70.4%) were at stage 3A and eight patients (29.6 %) were at stage 3B. 13 patients (48.1%) received adjuvant cisplatin-based chemotherapy. 3 patients (11.1%) received postoperative radiotherapy. The median follow-up time was 36 months. In all patients, the average DFS was 26.6 months. The average OS was 48 months. From the perspective of stage 3A and 3B; DFS (p = 0.379) and OS (p = 0.69) did not differ significantly in terms. 16 patients (59.3%) after receiving neoadjuvant chemotherapy was found viable tumor ratio equal and under 10% in the surgical pathology materials. 11 patients (40%) was found viable tumor above the rate of 10% . When considered from this point of view DFS (p = 0.16) and OS (p = 0.097) showed no difference. The DFS (p = 0.846) and OS (p = 0.6) was not different between patients who received adjuvant chemotherapy and who did not. Conclusions: In patients with stage III NSCLC who received neoadjuvant chemotherapy found longer OS and DFS durations than from literature. ERCC1 and RRM1 expressions that were predictive markers of response of the treatment for cisplatin and gemcitabine was not correlated to therapy and survival.
FRI-275-Fecal microbiota profiles as a diagnosis marker in PSC and PSC-IBD patients compare to healthy controls
Authors: Yelena Lapidot, Shira Ben-Simon, Oranit Cohen-ezra, Yana Davidov, Peretz Weiss, Mariya Likhter, Ella Veitsman, Omry Koren, Michal Safran, Ziv Ben Ari
Journal: Journal of Hepatology (2019)
Abstract 378: A Systematic Review of Mobility/Immobility in Thromboembolism Risk Assessment Models for Hospitalized Patients
Authors: Fan Ye, Carolyn Stalvey, Matheen Khuddus, David Winchester, Hale Toklu, Joseph Mazza, Steven Yale
Journal: Circulation Research (2017)

Introduction: Venous thromboembolism (VTE) is a potentially fatal disorder. Prophylaxis is often suboptimal in medical inpatients, attributed to the difficulty in identifying at-risk patients. Simple and validated risk-assessment models (RAMs) are available to assist clinicians in identifying and stratifying patients who have a higher likelihood for developing VTE. Despite the well-documented association of immobility with increased risk of thrombosis, immobility is not consistently defined in clinical studies. Methods: We conducted a systematic review of published RAMs, based on objective criteria, to determine how the term immobility is defined in RAMs. Results: We identified seventeen RAMs with six being externally validated. The concept of immobility is vaguely described in different RAMs, impacting the validity of these models in clinical practice. The widespread variability in defining mobility in RAMs precluded its accurate clinical application further limiting generalization of published RAMs. Conclusion: Externally validated RAMs with clearly defined qualitative or quantitative terms of immobility are needed to assess VTE risk in real-time at the point-of-care.
Magnetic Hydrogel with Optimally Adaptive Functions for Breast Cancer Recurrence Prevention
Authors: Fei Gao, Wensheng Xie, Yuqing Miao, Dan Wang, Zhenhu Guo, Anujit Ghosal, Yongsan Li, Yen Wei, Si‐Shen Feng, Lingyun Zhao, Hai Ming Fan
Journal: Advanced Healthcare Materials (2019)

Abstract Engineering biocompatible hydrogels using functional nanoparticles has attracted considerable attention because of their uniquely appealing cooperative effects that can enable multimodality imaging and treatment with improved efficacy against serious diseases. However, the effects of high‐content nanoparticle dopants on the rheological properties of hydrogels frequently lead to an unsatisfactory therapeutic result, which is particularly notable in the design of magnetic hydrogel formulations for cancer therapy. Herein is reported a novel magnetic hydrogel functionalized by ferromagnetic vortex‐domain iron oxide (FVIOs) with optimally adaptive functions for prevention of breast cancer recurrence. The FVIOs can perfectly incorporate into the dynamic hydrogel networks with an extremely low concentration (0.6 mg mL −1 ), 17 times lower than that of conventional superparamagnetic iron oxide nanoparticles with sufficient heating capacity. Such magnetic hydrogels exhibit high inductive heating and remarkable rheological properties simultaneously. Moreover, the self‐healing, self‐conformal ability, controlled release of loaded doxorubicin, biodegradation, and pH‐responsiveness of the magnetic hydrogel project their efficient sustainable therapeutic ability. In vivo postoperative treatment has further demonstrated the high efficacy of FVIO‐based magnetic hydrogels, as evidenced by the significant suppression of the local tumor recurrences compared to chemotherapy or hyperthermia alone. This unique magnetic hydrogel formulation with optimally adaptive functions shows strong potential in preventing relapses of various cancers.
SAT-013-Potentially Preventable readmissions and complications in hospitalized patients with hepatic encephalopathy in a large multi-center cohort
Authors: Jasmohan S Bajaj, Puneeta Tandon, Jacqueline O’leary, Florence Wong, Guadalupe Garcia-Tsao, Scott Biggins, Patrick S. Kamath, Paul J. Thuluvath, Jennifer Lai, Hugo E. Vargas, Ram Subramanian, Benedict Maliakkal, Michael Fallon, Leroy Thacker, Rajender Reddy
Journal: Journal of Hepatology (2019)
Gastroesophageal Reflux and Serum Biomarkers in Systemic Sclerosis–Associated Interstitial Lung Disease: Comment on the Article by Elhai et al
Authors: Sergey Moiseev, Antonina Sosnovskaya, Fatima Chotchaeva, Elena Shchegoleva, Pavel Novikov
Journal: Arthritis & Rheumatology (2019)
Role of chemokines in resectable non-small cell lung cancer (NSCLC)
Authors: M. Drosslerová, M. Šterclová, M. Vašáková, A. Tašková, V. Hytych, P. Horažďovský, E. Richterová, M. Smětáková, L. Havel
Journal: Annals of Oncology (2019)

Background: Complex network of chemokines is a part of immune reaction targeted against tumor cells. Chemokines influence cancer growth. It is not clear whether the concentrations of chemokines at the time of diagnosis of NSCLC reflect extent of the disease. Aim: To compare chemokine concentrations (CCL2, CCL8, CXCL12) in plasma of patients with resectable NSCLC to those without cancer. To find out whether the chemokine concentrations differ according to stage of the disease. Methods: We enrolled 69 patients undergoing surgery for proven/suspected NSCLC (37 males- mean age 66 years, 32 females- mean age 64 years). They underwent standard diagnostic and staging procedure to determine resectability (CT/PET-CT, bronchoscopy, ev. abdominal ultrasound), then surgery was made. We diagnosed 42 patients with NSCLC, 27 patients in the control group had benign lung pathologies (e.g. chondrohamatoma, fibrous tissue) and remained as the control group. We took plasma samples before surgery in treatment naive patients. The chemokine concentrations were assesed by ELISA LSBio Kits. The results were stated in pg/ml (CCL2, CCL8), ng/ml (CXCL12). Parametric statistics was used for results analysis. Results:Table8PCCL2 (pg/ml)pCCL8 (pg/ml)PCXCL12 (ng/ml)pNSCLC/benign lesions169,09/146,590,34556,22/48,840,4866,32/5,30,204NSCLCst. I/ benign lesions177,16/146,590,31049,66/48,840,9375,08/5,30,764NSCLCst.II+IIIa/ benign lesions163,65/146,590,53966,34/48,840,2347,82/5,30,017 Open table in a new tab Conclusions: Chemokine values did not differ in NSCLC versus control group. Patients with NSCLC stages II and IIIA had significantly higher CXCL12 concentrations than control group. This could be because CXCL12 promotes tumor growth and metastasis. Legal entity responsible for the study: The authors. Funding: Internal grant of Thomayer Hospital. Disclosure: All authors have declared no conflicts of interest.
Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT
Authors: Xina Zhang, Buqing Sai, Fan Wang, Lujuan Wang, Yuhui Wang, Leliang Zheng, Guiyuan Li, Jingqun Tang, Juanjuan Xiang
Journal: Molecular Cancer (2019)

Metastasis is the main cause of lung cancer mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) are a component of the cancer microenvironment and contribute to cancer progression. Intratumoral hypoxia affects both cancer and stromal cells. Exosomes are recognized as mediators of intercellular communication. Here, we aim to further elucidate the communication between BMSC-derived exosomes and cancer cells in the hypoxic niche. Exosomal miRNA profiling was performed using a microRNA array. Lung cancer cells and an in vivo mouse syngeneic tumor model were used to evaluate the effects of select exosomal microRNAs. Hypoxic BMSC-derived plasma exosomal miRNAs were assessed for their capacity to discriminate between cancer patients and non-cancerous controls and between cancer patients with or without metastasis. We demonstrate that exosomes derived from hypoxic BMSCs are taken by neighboring cancer cells and promote cancer cell invasion and EMT. Exosome-mediated transfer of select microRNAs, including miR-193a-3p, miR-210-3p and miR-5100, from BMSCs to epithelial cancer cells activates STAT3 signaling and increases the expression of mesenchymal related molecules. The diagnostic accuracy of individual microRNA showed that plasma exosomal miR-193a-3p can discriminate cancer patients from non-cancerous controls. A panel of these three plasma exosomal microRNAs showed a better diagnostic accuracy to discriminate lung cancer patients with or without metastasis than individual exosomal microRNA. Exosome-mediated transfer of miR-193a-3p, miR-210-3p and miR-5100, could promote invasion of lung cancer cells by activating STAT3 signalling-induced EMT. These exosomal miRNAs may be promising noninvasive biomarkers for cancer progression.
Effects of exercise training on papain-induced pulmonary emphysema in rats
Authors: C. Flo, F. D. T. Q. S. Lopes, D. Kasahara, A. C. Duarte Silva, R. C. Jesus, D. H. R. F. Rivero, Wilson Jacob Filho, Paulo Hilario Nascimento Saldiva, Mílton de Arruda Martins
Journal: American Journal of Respiratory and Critical Care Medicine (2004)