tbuckley/cabot-search huggingface dataset:
SAT-405-Genomic expression in circulating PBMCs of patients with hepatocellular carcinoma: Effect of ablative treatment
Authors: Palmieri Vincenzo, annamaria gesualdo, Marica Cariello, Antonio Moschetta, Francesca Passerini, Fabiana D’Onofrio, Enrica Settimo, Lucia Donatella Grimaldi, Piero Portincasa
Journal: Journal of Hepatology (2019)
THU-127-Clinical Practice experience with pan genotypic therapies glecaprevir-pibrentasvir and sofosbuvir-velpatasvir in the TRIO Network
Authors: Michael Curry, Bruce Bacon, Steven Flamm, Scott Milligan, Naoky Tsai, Nicole Wick, Zobair Younossi, Nezam Afdhal
Journal: Journal of Hepatology (2019)
FRI-211-Evaluation of the safety and tolerability of transaminase flares during antiviral therapy in patients with HBeAg negative chronic HBV infection or HBV/HDV co-infection
Authors: Michel Bazinet, Victor Pantea, Gheorghe Placinta, Iurie Moscalu, Valentin Cebotarescu, Lilia Cojuhari, Pavlina Jimbei, Liviu Iarovoi, Valentina Smesnoi, Tatiana Musteata, Alina Jucov, Adalbert Krawczyk, Andrew Vaillant
Journal: Journal of Hepatology (2019)
Characterization and potential role of PD-L1 positive lung cancer stem cells in lymph nodes metastasis
Authors: A. Raniszewska, E. Rutkowska, R. Sokolowski, J. Domagala-Kulawik
Journal: Annals of Oncology (2019)

Background: An immunotherapy was found to be effective in achieving long-term survival in some lung cancer patients and has emerged to searching for new immune biomarkers. It is suggested that lung cancer stem cells (LCSCs) are responsible for tumor initiation, maintenance and its metastatic potential. In our previous studies, we confirmed the presence of PD-L1 positive LCSCs (EPCAM+/CD133+) in metastatic lymph nodes (LNs). The aim of this study was to assess the presence of LCSCs in LNs aspirates using extended LCSCs markers and compare it with clinical data of patients. Methods: LCSCs were analyzed in LNs aspirates obtained during EBUS TBNA procedure. Flow cytometry with anti-CD44, anti-CXCR4 antibodies was applied to identify LCSCs. Additionally anti-PD-L1 was applied and geometric mean fluorescence (GMF) intensity of PD-L1 on LCSCs was measured. Results: 20 patients with confirmed non small cell lung cancer were enrolled. The highest proportion of PD-L1+ LCSCs was found in patients with metastatic disease; median values (p25-75)- 4,76% (1,51-7,65%) versus non metastatic- 0.01% (0-0,13%), p < 0.05. Higher percentage of PD-L1 positive LCSCs was found in patients with EGFR mutations and ALK rearrangements than in those without oncogenic addiction, p < 0.05. We observed significant correlation between proportion of PD-L1+ LCSCs and pack years smoked (r = 0.76, p < 0.05) and between expression (GMF) of PD-L1 and pack years smoked (r = 0.67, p < 0.05). Conclusions: We confirmed the significance of LCSCs in tumor growth and aggressiveness. LCSCs may serve as a potential strategy to enhance cancer immunotherapy efficacy. The development of predictive biomarkers is needed to optimize patient benefit and guide combination approaches. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 15186: Simple Sarcopenia Screening Test is Useful to Predict Future Adverse Events in Male Patients With Cardiovascular Risk
Authors: Yoshiro Onoue, Yasuhiro Izumiya, Shinsuke Hanatani, Tomoko Tanaka, Satoru Yamamura, Yuichi Kumura, Satoshi Araki, Hisao Ogawa
Journal: Circulation (2015)

Introduction: Progressive loss of skeletal muscle termed “sarcopenia” is an independent risk factor for mortality in patients with cardiovascular diseases. Recently, a simple screening test that can identify sarcopenia using three variables (age, grip strength and calf circumference) has been developed. We utilized the screening test and assessed its clinical utility in patients with cardiovascular risk. Hypothesis: Simple sarcopenia screening test predicts future adverse events in patients with cardiovascular risk. Methods and Results: The study included 479 patients who have one or more risk factors. The sarcopenia screening score was calculated, and the patients were divided into sarcopenia (n=260) and non-sarcopenia (n=219) group. The sarcopenia group had significantly higher BNP, E/e’, and lower estimated glomerular filtration rate (eGFR) than the non-sarcopenia group. Multivariate linear regression analyses showed that the sarcopenia score correlated significantly with BNP independent of age, sex, hypertension, diabetes mellitus, and eGFR. In multivariate Cox proportional hazards analysis, BNP (ln[BNP]) (hazard ratio [HR]: 2.17; 95% confidence interval [CI]: 1.42-3.32, p&lt;0.01), body mass index (HR: 1.23; 95%CI: 1.05-1.45; p=0.01), NYHA functional classification (HR: 2.84; 95%CI: 1.63-4.95, p&lt;0.01) and the presence of sarcopenia (HR: 2.88; 95%CI: 1.06-7.82; p=0.04) were independent predictors of heart failure re-hospitalization. With regard to the gender difference, Kaplan-Meier curve revealed that event free survival rate was significantly lower only in the male, but not female sarcopenia group. In addition, serum brain-derived neurotrophic factor, known as a brain and skeletal muscle-derived protein, were significantly lower in the male sarcopenia group than non-sarcopenia group. Conclusions: Simple sarcopenia screening test could predict the future adverse events in male patients with cardiovascular risk.
EGFR mutations in Latinos from the United States and Latin America.
Authors: Ariel Lopez-Chavez, Moses Evbuomwan, Liqiang Xi, Guinevere Chun, Tatiana Vidaurre, Oscar Arrieta, George Oblitas, Ana Belen Oton, Alejandro R. Calvo, Arun Rajan, Pooja Amarapurkar, Mark Raffeld, Seth M. Steinberg, Lorena Arze-Aimaretti, Giuseppe Giaccone
Journal: Journal of Clinical Oncology (2015)

8070 Background: Activating mutations in the epidermal growth factor receptor gene (EGFR) confer hypersensitivity to EGFR tyrosine kinase inhibitors in patients with advanced non–small-cell lung cancer (NSCLC). Racial and ethnic differences in the frequency of such mutations have been previously described; however, there are limited and conflicting reports on its frequency in the Latino population. Methods: We collected samples from 642 patients with NSCLC from 7 institutions in the US and Latin-America. Activating EGFR mutation analysis of exons 18 through 21 was performed at 2 CLIA certified central laboratories. Statistical analyses were performed using Fisher’s exact test or Mehta’s modification to Fisher’s exact test to determine relationships among parameters. All p-values are two-tailed and reported without adjustment for multiple comparisons. Results: EGFR mutation analysis was successfully performed in 480 of 642 patients (75%) of which 90 (19%) were Latinos, 318 (66%) non-Latino Whites, 35 (7%) non-Latino Asians, 30 (6%) non-Latino Blacks and 7 (2%) from other race/ethnicities. EGFR mutations were found in 21 of 90 (23%) Latino patients and its frequency varied according to country of origin. The highest frequency was observed in Latinos from Peru (37%) followed by US (23%), Mexico (18%), Venezuela (10%) and Bolivia (8%). In Latinos never smokers and Latinos with adenocarcinoma histology, the frequency of EGFR mutations was 38% and 30% respectively. There was a significant difference in the frequency of EGFR mutations among the different racial/ethnic subgroups analyzed (p < 0.001) with non-Latino Asians having the highest frequency (57%) followed by Latinos (23%), non-Latino Whites (19%) and non-Latino Blacks (10%). However, there was no difference between Latinos (23%) and non-Latinos (22%) (p = 0.78) and Latinos and non-Latino Whites (p = 0.37). While patients from Peru had an overall higher frequency of mutations (37%) than all other Latinos (17%), such difference was not statistically significant (p = 0.06) and diminished greatly when smoking and adenocarcinoma histology subgroups were analyzed independently. Conclusions: There was no significant difference between the frequency of EGFR mutations in NSCLC in Latinos and non-Latinos.
Gut Microbial Associations to Plasma Metabolites Linked to Cardiovascular Phenotypes and Risk
Authors: Alexander Kurilshikov, Inge C.L. van den Munckhof, Lianmin Chen, Marc J. Bonder, Kiki Schraa, Joost H.W. Rutten, Niels P. Riksen, Jacqueline de Graaf, Marije Oosting, Serena Sanna, Leo A.B. Joosten, Marinette van der Graaf, Tessa Brand, Debby P.Y. Koonen, Martijn van Faassen, P. Eline Slagboom, Ramnik J. Xavier, Folkert Kuipers, Marten H. Hofker, Cisca Wijmenga, Mihai G. Netea, Alexandra Zhernakova, Jingyuan Fu
Journal: Circulation Research (2019)

Rationale: Altered gut microbial composition has been linked to cardiovascular diseases (CVDs), but its functional links to host metabolism and immunity in relation to CVD development remain unclear. Objectives: To systematically assess functional links between the microbiome and the plasma metabolome, cardiometabolic phenotypes, and CVD risk and to identify diet-microbe-metabolism-immune interactions in well-documented cohorts. Methods and Results: We assessed metagenomics-based microbial associations between 231 plasma metabolites and microbial species and pathways in the population-based LLD (Lifelines DEEP) cohort (n=978) and a clinical obesity cohort (n=297). After correcting for age, sex, and body mass index, the gut microbiome could explain ≤11.1% and 16.4% of the variation in plasma metabolites in the population-based and obesity cohorts, respectively. Obese-specific microbial associations were found for lipid compositions in the VLDL, IDL, and LDL lipoprotein subclasses. Bacterial L-methionine biosynthesis and a Ruminococcus species were associated to cardiovascular phenotypes in obese individuals, namely atherosclerosis and liver fat content, respectively. Integration of microbiome-diet-inflammation analysis in relation to metabolic risk score of CVD in the population cohort revealed 48 microbial pathways associated to CVD risk that were largely independent of diet and inflammation. Our data also showed that plasma levels rather than fecal levels of short-chain fatty acids were relevant to inflammation and CVD risk. Conclusions: This study presents the largest metagenome-based association study on plasma metabolism and microbiome relevance to diet, inflammation, CVD risk, and cardiometabolic phenotypes in both population-based and clinical obesity cohorts. Our findings identified novel bacterial species and pathways that associated to specific lipoprotein subclasses and revealed functional links between the gut microbiome and host health that provide a basis for developing microbiome-targeted therapy for disease prevention and treatment.
FRI-277-Effect of probiotics in the treatment of NASH: A randomized clinical trial
Authors: Gabriela Port, Cristiane Tovo, Sabrina Fernandes, Alessandra Peres, Gilson Dornelles, Giselle Pinto, Vanessa Houde, Thibault Varin, Genevieve Pilon, Andre Marette, Caroline Buss
Journal: Journal of Hepatology (2019)
Cellular Senescence in the Kidney
Authors: Marie-Helena Docherty, Eoin D. O’Sullivan, Joseph V. Bonventre, David A. Ferenbach
Journal: Journal of the American Society of Nephrology (2019)

Senescent cells have undergone permanent growth arrest, adopt an altered secretory phenotype, and accumulate in the kidney and other organs with ageing and injury. Senescence has diverse physiologic roles and experimental studies support its importance in nephrogenesis, successful tissue repair, and in opposing malignant transformation. However, recent murine studies have shown that depletion of chronically senescent cells extends healthy lifespan and delays age-associated disease—implicating senescence and the senescence-associated secretory phenotype as drivers of organ dysfunction. Great interest is therefore focused on the manipulation of senescence as a novel therapeutic target in kidney disease. In this review, we examine current knowledge and areas of ongoing uncertainty regarding senescence in the human kidney and experimental models. We summarize evidence supporting the role of senescence in normal kidney development and homeostasis but also senescence-induced maladaptive repair, renal fibrosis, and transplant failure. Recent studies using senescent cell manipulation and depletion as novel therapies to treat renal disease are discussed, and we explore unanswered questions for future research.
PS-102-Circulating native albumin in patients with cirrhosis admitted to hospital for acute decompensation and acute-on-chronic liver failure: Relation to serum albumin levels, albumin function, and patient outcomes
Authors: Maurizio Baldassarre, Marina Naldi, Michele Bartoletti, Agnese Antognoli, Maristella Laggetta, Martina Gagliardi, Giacomo Zaccherini, Giulia Iannone, Dario Pratelli, Marco Domenicali, Katja Waterstradt, Manuela Bartolini, Franco Trevisani, Mauro Bernardi, Paolo Caraceni
Journal: Journal of Hepatology (2019)
Active Site-Induced Evolutionary Constraints Follow Fold Polarity Principles in Soluble Globular Enzymes
Authors: Alexander Mayorov, Matteo Dal Peraro, Luciano A Abriata
Journal: Molecular Biology and Evolution (2019)

A recent analysis of evolutionary rates in >500 globular soluble enzymes revealed pervasive conservation gradients toward catalytic residues. By looking at amino acid preference profiles rather than evolutionary rates in the same data set, we quantified the effects of active sites on site-specific constraints for physicochemical traits. We found that conservation gradients respond to constraints for polarity, hydrophobicity, flexibility, rigidity and structure in ways consistent with fold polarity principles; while sites far from active sites seem to experience no physicochemical constraint, rather being highly variable and favoring amino acids of low metabolic cost. Globally, our results highlight that amino acid variation contains finer information about protein structure than usually regarded in evolutionary models, and that this information is retrievable automatically with simple fits. We propose that analyses of the kind presented here incorporated into models of protein evolution should allow for better description of the physical chemistry that underlies molecular evolution.
Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial
Authors: Sebastian Michels, Bartomeu Massutí, Hans-Ulrich Schildhaus, Jeremy Franklin, Martin Sebastian, Enriqueta Felip, Christian Grohé, Delvys Rodriguez-Abreu, Diana S.Y. Abdulla, Helge Bischoff, Christian Brandts, Enric Carcereny, Jesús Corral, Anne-Marie C. Dingemans, Eva Pereira, Jana Fassunke, Rieke N. Fischer, Masyar Gardizi, Lukas Heukamp, Amelia Insa, Anna Kron, Roopika Menon, Thorsten Persigehl, Martin Reck, Richard Riedel, Sacha I. Rothschild, Andreas H. Scheel, Matthias Scheffler, Petra Schmalz, Egbert F. Smit, Meike Limburg, Mariano Provencio, Niki Karachaliou, Sabine Merkelbach-Bruse, Martin Hellmich, Lucia Nogova, Reinhard Büttner, Rafael Rosell, Jürgen Wolf
Journal: Journal of Thoracic Oncology (2019)
SAT-269-The sustained deleterious impact of viremia on patient reported outcomes in patients with chronic hepatitis C who don’t achieve sustained virologic response
Authors: Zobair Younossi, Maria Stepanova, Andrei Racilla, Arian Afendy, Ira Jacobson, Andrew Muir, Stanislas Pol, Stefan Zeuzem, Eric Lawitz, Anuj Gaggar, Robert Myers, Issah Younossi, Fatema Nader
Journal: Journal of Hepatology (2019)
Genetic Testing and Results in a Population-Based Cohort of Breast Cancer Patients and Ovarian Cancer Patients
Authors: Allison W. Kurian, Kevin C. Ward, Nadia Howlader, Dennis Deapen, Ann S. Hamilton, Angela Mariotto, Daniel Miller, Lynne S. Penberthy, Steven J. Katz
Journal: Journal of Clinical Oncology (2019)

Genetic testing for cancer risk has expanded rapidly. We examined clinical genetic testing and results among population-based patients with breast and ovarian cancer.The study included all women 20 years of age or older diagnosed with breast or ovarian cancer in California and Georgia between 2013 and 2014 and reported to the SEER registries covering the entire state populations. SEER data were linked to results from four laboratories that performed nearly all germline cancer genetic testing. Testing use and results were analyzed at the gene level.There were 77,085 patients with breast cancer and 6,001 with ovarian cancer. Nearly one quarter of those with breast cancer (24.1%) and one third of those with ovarian cancer (30.9%) had genetic test results. Among patients with ovarian cancer, testing was lower in blacks (21.6%; 95% CI, 18.1% to 25.4%; v whites, 33.8%; 95% CI, 32.3% to 35.3%) and uninsured patients (20.8%; 95% CI, 15.5% to 26.9%; v insured patients, 35.3%; 95% CI, 33.8% to 36.9%). Prevalent pathogenic variants in patients with breast cancer were BRCA1 (3.2%), BRCA2 (3.1%), CHEK 2 (1.6%), PALB2 (1.0%), ATM (0.7%), and NBN (0.4%); in patients with ovarian cancer, prevalent pathogenic variants were BRCA1 (8.7%), BRCA2 (5.8%), CHEK2 (1.4%), BRIP1 (0.9%), MSH2 (0.8%), and ATM (0.6%). Racial/ethnic differences in pathogenic variants included BRCA1 (ovarian cancer: whites, 7.2%; 95% CI, 5.9% to 8.8%; v Hispanics, 16.1%; 95% CI, 11.8% to 21.2%) and CHEK2 (breast cancer: whites, 2.3%; 95% CI, 1.8% to 2.8%; v blacks, 0.1%; 95% CI, 0% to 0.8%). When tested for all genes that current guidelines designate as associated with their cancer type, 7.8% of patients with breast cancer and 14.5% of patients with ovarian cancer had pathogenic variants.Clinically-tested patients with breast and ovarian cancer in two large, diverse states had 8% to 15% prevalence of actionable pathogenic variants. Substantial testing gaps and disparities among patients with ovarian cancer are targets for improvement.
Efficacy and safety of adjuvant chemotherapy in lung cancer: Real-world evidence
Authors: F.S.R. Roitberg, M.F.B.V. Neffá, R.R.C.C. Bonadio, G. Harada, E.Z. Mendoza, M.P. Mak, T.K. Takahashi, R.E. Martins, C. Mesquita, F.C. Santini, P.H.X.N. de Araújo, L.L. Lauricella, G.F. Prado, T.Y. Takagaki, E.S. de Mello, F. Gabrielli, H.D.A. de Andrade Carvalho, R.M. Terra, G. de Castro
Journal: Annals of Oncology (2019)

Background: Platinum-based adjuvant chemotherapy (CT) improves survival in surgically resected non-small-cell lung cancer (NSCLC) patients (pts). However, cisplatin and vinorelbine (PV), the most studied regimen, is often associated with increased rates of grade 3-4 toxicities. We aimed to study the efficacy and safety of adjuvant CT in NSCLC pts in a real-world scenario. Methods: We performed a retrospective analysis of NSCLC pts treated with surgery with curative intent between 2009 and 2018 in an academic cancer center. After surgery, pts were accessed to receive adjuvant CT, based on physicians' discretion. Electronic records were reviewed and data were collected for pts and tumor characteristics, treatments, outcomes (overall survival [OS] and disease-free survival [DFS]), and toxicities. OS and DFS were estimated by the Kaplan-Meier method, and curves were compared by log-rank. Prognostic factors were evaluated using Cox regression. Results: 250 consecutive pts were studied: 80 adjuvant CT and 170 observation; 55/80 received PV. Median age 65 years, 62% adenocarcinoma and 28% squamous cell carcinoma. The observation group differed from the adjuvant CT group in terms of type of surgery (lobectomy, 88% vs 76%; p = .020), 7th ed TNM staging (I, 50% vs 2%; II, 29% vs 45%; III, 20% vs 42%; p < .001), and lymph node status (N0, 71% vs 31%; p < .001). After a median follow-up of 24 months (mo), median DFS was 56.0 vs 39.3 mo in CT and observation groups, and median OS was 61.4 vs 58.5 mo, respectively. In an adjusted analysis, adjuvant CT was associated with improved DFS (HR 0.36, IC 95% 0.23-0.58; p < .001) and OS (HR 0.47, IC 95% 0.28-0.78; p .004). Toxicities were high in the PV group: 49% of the pts required hospitalization, 45% discontinued treatment, and 89% presented grade 3-4 toxicities, including 29% of febrile neutropenia. Five pts (9%) had treatment-related deaths. Conclusions: Our study supports both the OS and DFS benefits of NSCLC adjuvant CT in the real world scenario. However, PV was associated with alarming rates of treatment-related toxicities and deaths, suggesting that new adjuvant avenues are warranted. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
HOXB13 networking with ABCG1/EZH2/Slug mediates metastasis and confers resistance to cisplatin in lung adenocarcinoma patients
Authors: Jun Zhan, Peng Wang, Shuai Li, Jiagui Song, Huiying He, Yunling Wang, Zhaofei Liu, Fan Wang, Hua Bai, Weigang Fang, Quan Du, Min Ye, Zhijie Chang, Jie Wang, Hongquan Zhang
Journal: Theranostics (2019)

Rationale: Distant metastasis and chemoresistance are the major causes of short survival after initial chemotherapy in lung adenocarcinoma patients.However, the underlying mechanisms remain elusive.Our pilot study identified high expression of the homeodomain transcription factor HOXB13 in chemoresistant lung adenocarcinomas.We aimed to investigate the role of HOXB13 in mediating lung adenocarcinoma chemoresistance.Methods: Immunohistochemistry assays were employed to assess HOXB13 protein levels in 148 non-small cell lung cancer patients.The role of HOXB13 in lung adenocarcinoma progression and resistance to cisplatin therapy was analyzed in cells, xenografted mice, and patient-derived xenografts.Needle biopsies from 15 lung adenocarcinoma patients who were resistant to cisplatin and paclitaxel therapies were analyzed for HOXB13 and EZH2 protein levels using immunohistochemistry. Results: High expression of HOXB13 observed in 17.8% of the lung adenocarcinoma patients in this study promoted cancer progression and predicted poor prognosis.HOXB13 upregulated an array of metastasis-and drug-resistance-related genes, including ABCG1, EZH2, and Slug, by directly binding to their promoters.Cisplatin induced HOXB13 expression in lung adenocarcinoma cells, and patient-derived xenografts and depletion of ABCG1 enhanced the sensitivity of lung adenocarcinoma cells to cisplatin therapy.Our results suggest that determining the combined expression of HOXB13 and its target genes can predict patient outcomes.Conclusions: A cisplatin-HOXB13-ABCG1/EZH2/Slug network may account for a novel mechanism underlying cisplatin resistance and metastasis after chemotherapy.Determining the levels of HOXB13 and its target genes from needle biopsy specimens may help predict the sensitivity of lung adenocarcinoma patients to platinum-based chemotherapy and patient outcomes.