tbuckley/cabot-search huggingface dataset:
Digital <i>Fusion-Gene</i> expression profiling in acute leukemia (AL): Clinical validation of throughput molecular technology in laboratory medicine.
Authors: Ariz Akhter, Fariborz Rashid-Kolvear, Fahad Farooq, Abid Qureshi, Meer-Taher Shabani-Rad, Gary Sinclair, Douglas Allan Stewart, Adnan Mansoor
Journal: Journal of Clinical Oncology (2015)

7066 Background: AL is a heterogenous and aggressive disease with dismal prognosis. Chromosomal translocations constitute the basis of current WHO classification and are central to AL pathogenesis. FISH technique is utilized to detect variable translocations for patient prognosis and therapy selection. It is a labor intensive and expensive technique, which may not support rapidly expanding scope of additional translocations of clinical importance in AL patients. Hence, throughput automated technologies may play a critical in the management of AL patients. Methods: Nanostring platform utilizes a novel digital color-coded automated technology that is based on direct multiplexed measurement of gene expression. The “nCounter Leukemia Fusion Gene Expression Assay Kit” allows profiling a comprehensive set of 25 fusion genes that result from balanced translocations in AL. It also includes probes for 12 clinically proven AL-related biomarkers. RNA extracted from FFPE tissue from 50 AL patients with known balanced chromosomal translocations and validated the fusion gene expression on this platform. Results: We observed highly significant concordance between Nanostring fusion gene results with FISH data in various translocation such as t(9;22) (BCR-ABL); t(15;17) PML-RARA; t(8;21) (AML-ETO); t(4;11) (MLL-AF4) and Inv(16) (CBFB-MYH11) (P< 0.05). Nanostring technology failed to validate fusion gene transcript in patients with t(12;21) (TEL-AML). High expression of BAALC, a prognostic biomarker associated with poor outcome in AL patients was noted in t(9;22) (58%), t(15;17) (12%), t(4;11) (50%), t(12, 21) (20%), t(8;21) (20% ) and Inv(16) (63%). Conclusions: We have validated the application of automated throughput technology for AL patients in a clinical laboratory. Our study provides an efficient, viable and economical solution for the rapidly expanding molecular repertoire of laboratory testing for AL patients, which is critical to determine prognosis and select effective therapy. This approach also provides a promise to seamlessly incorporate newly discovered (up to 800) targets of diagnostic and prognostic importance on this digital platform.
Quantitative Lipidomics in Pulmonary Alveolar Proteinosis
Authors: Matthias Griese, Francesco Bonella, Ulrich Costabel, Jacques de Blic, Nguyen-Binh Tran, Gerhard Liebisch
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Pulmonary alveolar proteinosis (PAP) is characterized by filling of the alveolar spaces by lipoprotein-rich material of ill-defined composition, and is caused by molecularly different and often rare diseases that occur from birth to old age.Objectives: To perform a quantitative lipidomic analysis of lipids and the surfactant proteins A, B, and C in lavage fluids from patients with proteinosis of different causes in comparison with healthy control subjects.Methods: During the last two decades, we have collected BAL samples from patients with PAP due to autoantibodies against granulocyte-macrophage colony-stimulating factor; genetic mutations in CSF2RA (colony-stimulating factor 2 receptor α-subunit), MARS (methionyl aminoacyl-tRNA synthetase), FARSB (phenylalanine-tRNA synthetase, β-subunit), and NPC2 (Niemann-Pick disease type C2); and secondary to myeloid leukemia. Their lipid composition was quantified.Measurements and Main Results: Free cholesterol was largely increased by 60-fold and cholesteryl esters were increased by 24-fold. There was an excessive, more than 130-fold increase in ceramide and other sphingolipids. In particular, the long-chain ceramides d18:1/20:0 and d18:1/24:0 were elevated and likely contributed to the proapoptotic environment observed in PAP. Cellular debris lipids such as phosphatidylethanolamine and phosphatidylserine were only moderately increased, by four- to sevenfold. The surfactant lipid class phosphatidylcholine expanded 17-fold, lysophosphatidylcholine expanded 54-fold, and the surfactant proteins A, B, and C expanded 144-, 4-, and 17-fold, respectively. These changes did not differ among the various diseases that cause PAP.Conclusions: This insight into the alveolar lipidome may provide monitoring tools and lead to new therapeutic strategies for PAP.
Abstract 13726: The Ryanodine Receptor Stabilizer S44121 / Arm036 Improves Peripheral and Respiratory Muscle Function in a Mouse Model of Heart Failure
Authors: Marion Pauly, Stefan Matecki, Jerome Thireau, Muriel Bouly, Jerome Roussel, Sylvain Richard, Alain Lacampagne
Journal: Circulation (2014)

Background: Congestive heart failure (CHF) is associated with progressive skeletal muscle dysfunction (reduced exercise capacity and increased fatigability). Type 1 ryanodine receptor (RyR1) is the...
Abstract A61: Identification of therapeutic proteins in venom gland of Ectatomma opaciventre for head and neck tumor therapy
Authors: Ângela das Neves Oliveira, Lucas Ian Veloso Correia, Lídia Maria Rebolho Batista Arantes, Ana Carolina de Carvalho, Elisa Alves Messias, Bruna Pereira Sorroche, Flávia Coltri Eguchi, Renata Santos Rodrigues, Matias Eliseo Melendez, André Lopes Carvalho
Journal: Clinical Cancer Research (2018)

Abstract Background: Head and neck cancer is the sixth most common cancer site worldwide and is associated with low survival and high mortality rates, when diagnosed in advanced stages. The pursuit for potential therapeutic targets in natural resources may lead to the development of new antineoplastic agents. Several compounds coming from venomous animals are being tested in clinical trials due to their high selectivity and different physiologic activities. In this way, ant-venom glands are composed of bioactive molecules, such as peptides/proteins and allergens, which may be considered as potential therapeutic agents for oncology. Objectives: The aim was to identify potential therapeutic proteins expressed in venomous glands of Ectatomma opaciventre ants, for the treatment of head and neck squamous cell carcinoma (HNSCC) tumors. Materials and Methods: The mRNA library of Ectatomma opaciventre was sequenced using Illumina NextSeq 500 platform (76 bp unpaired-end) and NextSeq 500/550 Mid Output v2 kit (150 cycles). Libraries were constructed using TruSeq Stranded mRNA LT Sample Prep Kit (Illumina). A de novo assembly of the Ectatomma opaciventre transcriptome was performed using Velvet software. Results: The RNA-seq of E. opaciventre venom gland generated 55,131,904 raw reads. The de novo Velvet assembly produced 23,254 contigs, which matched against 12,061 NCBI-Blastn transcripts. From these contigs, 437 full-length transcripts were identified, from which two potential therapeutic genes were selected: SPARC and Phospholipase B. Both SPARC and Phospholipase B genes have been previously described as having antitumor properties. Conclusions: In conclusion, this deep transcriptome sequencing may have identified two potential therapeutic proteins, which are being analyzed in HNSCC cell lines. Citation Format: Ângela das Neves Oliveira, Lucas Ian Veloso Correia, Lídia Maria Rebolho Batista Arantes, Ana Carolina de Carvalho, Elisa Alves Messias, Bruna Pereira Sorroche, Flávia Coltri Eguchi, Renata Santos Rodrigues, Matias Eliseo Melendez, André Lopes Carvalho. Identification of therapeutic proteins in venom gland of Ectatomma opaciventre for head and neck tumor therapy [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A61.
SAT-318-Comparative accuracy of NAFLD fibrosis score, apri score, and FIB-4 score in predicting significant fibrosis in African Americans and Caucasians with non-alcoholic fatty liver disease
Authors: Hemnishil Marella, Surosree Ganguli, Yala Kirthi Reddy, Peter Snell, Brian Murphy, Pradeep Podila, Anna Jones, Yu Jiang, Satish Kedia, Uchenna Agbim, Benedict Maliakkal, Satheesh Nair, Sanjaya Satapathy
Journal: Journal of Hepatology (2019)
Addressing the Sexually Transmitted Infection and HIV Syndemic
Authors: Monica Gandhi, Matthew A. Spinelli, Kenneth H. Mayer
Journal: JAMA (2019)

The HIV and sexually transmitted infection (STI) epidemics, which have always been and will always be intertwined, are at an inflection point. Two scientific advancements over the last decade have substantially influenced the sexual health of people living with HIV and individuals at risk for HIV.
Finding missed cases of familial hypercholesterolemia in health systems using machine learning
Authors: Juan M. Banda, Ashish Sarraju, Fahim Abbasi, Justin Parizo, Mitchel Pariani, Hannah Ison, Elinor Briskin, Hannah Wand, Sebastien Dubois, Kenneth Jung, Seth A. Myers, Daniel J. Rader, Joseph B. Leader, Michael F. Murray, Kelly D. Myers, Katherine Wilemon, Nigam H. Shah, Joshua W. Knowles
Journal: npj Digital Medicine (2019)

Familial hypercholesterolemia (FH) is an underdiagnosed dominant genetic condition affecting approximately 0.4% of the population and has up to a 20-fold increased risk of coronary artery disease if untreated. Simple screening strategies have false positive rates greater than 95%. As part of the FH Foundation's FIND FH initiative, we developed a classifier to identify potential FH patients using electronic health record (EHR) data at Stanford Health Care. We trained a random forest classifier using data from known patients (n = 197) and matched non-cases (n = 6590). Our classifier obtained a positive predictive value (PPV) of 0.88 and sensitivity of 0.75 on a held-out test-set. We evaluated the accuracy of the classifier's predictions by chart review of 100 patients at risk of FH not included in the original dataset. The classifier correctly flagged 84% of patients at the highest probability threshold, with decreasing performance as the threshold lowers. In external validation on 466 FH patients (236 with genetically proven FH) and 5000 matched non-cases from the Geisinger Healthcare System our FH classifier achieved a PPV of 0.85. Our EHR-derived FH classifier is effective in finding candidate patients for further FH screening. Such machine learning guided strategies can lead to effective identification of the highest risk patients for enhanced management strategies.
FRI-138-HBVcore-versus HBVpolymerase-specific CD8+ T cells differ in chronically HBV-infected patients
Authors: Kathrin Heim, Anita Schuch, Elahe Salimi Alizei, Janine Kemming, Hendrik Luxenburger, Christoph Neumann-Haefelin, Maike Hofmann, Robert Thimme
Journal: Journal of Hepatology (2019)
SAT-171-HEV seroprevalence in blood donors in Turkey: Comparison of two commercial anti-HEV total Ab ELISA kit
Authors: Osman Yaşar, Güniz Cengiz, Ersin Karatayli, Mehtap Kizilpinar, Esra Yurdcu, Rabia Albayrak, Aysel Guven, Önder Arslan, Zeynep Ceren Karahan, Baris Otlu, Huseyin Guducuoglu, Selma Gökahmetoglu, Elife Berk, Özlem Gitmisoglu, Rüchan Sertöz, Cihan Yurdaydin, MITHAT Bozdayi, Senem Ceren Karatayli
Journal: Journal of Hepatology (2019)
THU-049-Impaired adaptive immunity is an early event in liver cirrhosis preceding acute-on-chronic liver failure
Authors: Sabrina Rueschenbaum, Sandra Ciesek, Alexander Queck, Marek Widera, Katharina Schwarzkopf, Bernhard Brüne, Christoph Welsch, Stefan Zeuzem, Andreas Weigert, Christian Lange
Journal: Journal of Hepatology (2019)
PS-018-Paroxysmal nocturnal hemoglobinuria and Budd Chiari syndrome: Impact of Eculizumab therapy on survival and liver outcome in 54 patients: A multicentric valdig study
Authors: Aurélie Plessier, Bun René, Anna Baiges, Akash Shukla, garcia pagan juan carlos, Dominique Valla, Deraucourt Emmanuelle, Isabelle Ollivier-Hourmand, Jean Paul Cervoni, Victor De Ledinghen, Tazi Zoubida, nousbaum jean baptiste, Bureau christophe, Christine Silvain, Tournilhac Olivier, Gerfaud valentin mathieu, François Durand, Gerard Socie, Odile Goria, Tellez luis, Agustin Albillos, Stefania Gioia, Oliviero Riggio, Payance Audrey, Andrea De Gottardi, PE Rautou, Peffault de la tour Regis, gault nathalie, Sicre Flore
Journal: Journal of Hepatology (2019)
Transient Introduction of miR-294 in the Heart Promotes Cardiomyocyte Cell Cycle Reentry After Injury
Authors: Austin Borden, Justin Kurian, Emily Nickoloff, Yijun Yang, Constantine D. Troupes, Jessica Ibetti, Anna Maria Lucchese, Erhe Gao, Sadia Mohsin, Walter J. Koch, Steven R. Houser, Raj Kishore, Mohsin Khan
Journal: Circulation Research (2019)

Embryonic heart is characterized of rapidly dividing cardiomyocytes required to build a working myocardium. Cardiomyocytes retain some proliferative capacity in the neonates but lose it in adulthood. Consequently, a number of signaling hubs including microRNAs are altered during cardiac development that adversely impacts regenerative potential of cardiac tissue. Embryonic stem cell cycle miRs are a class of microRNAs exclusively expressed during developmental stages; however, their effect on cardiomyocyte proliferation and heart function in adult myocardium has not been studied previously.
THU-189-Role of comorbidites in sofosbuvir-based treatment response: Clinical experience from an Italian real life cohort
Authors: Vitor Hugo Martins, Giulia Troshina, Giulia Verzon, Michela Ciruolo, Felice Rizzi, Claudia Chialà, Ludovica Venezia, Pablo Cortegoso Valdivia, Federico Cravero, Stefano Rizza, Giorgio Maria Saracco, Alessia Ciancio
Journal: Journal of Hepatology (2019)
Abstract 14662: Targeted Delivery of an Anti-miR to Cardiomyocytes Using Ultrasound and Microbubbles Suppresses Hypertrophy
Authors: Jonathan A Kopechek, Andrew R Carson, Charles F McTiernan, Xucai Chen, Rafey Feroze, Linda Lavery, Bima Hasjim, Flordeliza S Villanueva
Journal: Circulation (2015)

Introduction: MicroRNAs (miRs) are dysregulated in various cardiovascular diseases and anti-miRs have been developed to therapeutically inhibit the activity of specific miRs. An anti-miR against miR-23a suppressed hypertension-induced cardiac hypertrophy in preclinical models, but clinical translation is limited by a lack of targeted cardiac delivery systems. Ultrasound (US) targeted microbubble (MB) destruction (UTMD) is a novel therapeutic delivery platform that utilizes MBs as nucleic acid carriers. We hypothesized that UTMD-mediated delivery of anti-miR-23a suppresses cardiomyocyte hypertrophy and assessed UTMD-mediated functional delivery of anti-miR-23a to cultured cardiomyocytes (CMs) in vitro to lay the groundwork for future in vivo translational studies. Methods: Neonatal CMs were isolated from hearts of 1 to 2 day old Sprague Dawley rats. MBs were loaded with LNA-modified negative control anti-miR (NC) or anti-miR-23a, added to CM cultures (anti-miR concentration 300 pM) and insonified with a clinical US imaging system (1.3 MHz, MI setting=1.6). CMs were exposed to 100 μM phenylephrine (PE) to induce hypertrophy. Levels of miR-23a and FOXO3a (miR-23a target) were assessed by qRT-PCR 48 hr after UTMD and normalized to that in NC treated CMs. To quantify hypertrophy, CM surface areas pre- and post-PE were measured by a blinded observer. Results: UTMD treatment with anti-miR-23a knocked down CM miR-23a levels by 51 ± 24% compared to UTMD treatment with NC (N=5-6 per group, p &lt; 0.01). Expression of FOXO3a mRNA (miR-23a target) was 47 ± 16% higher following UTMD-mediated anti-miR-23a delivery compared to NC (N=3 per group, p &lt; 0.05). The increase in CM surface area upon PE exposure was 22 ± 13% less with UTMD-mediated anti-miR-23a delivery compared to NC (N=3 per group, p &lt; 0.05). Conclusions: To our knowledge, this is the first study of UTMD-mediated modulation of miR levels in cardiac tissue with an anti-miR. UTMD mediated delivery of anti-miR-23a to CMs caused knockdown of miR-23a levels, restored expression of downstream target mRNA levels, and suppression of CM hypertrophy. These results lay important groundwork for future in vivo studies leading to targeted clinical strategies to therapeutically modulate miRNA activity in the human heart.
SAT-165-Identification of chromatin-accessible domains on the host genome and hepatitis B virus mini-chromosome in infected primary human hepatocytes
Authors: Oceane Floriot, Giuseppe Rubens Pascucci, Matteo Pallocca, Francesca de Nicola, Michel Rivoire, Marie-Laure Plissonnier, Mirjam Zeisel, Massimo Levrero, Francesca Guerrieri
Journal: Journal of Hepatology (2019)
SAT-395-Bone marrow-mesenchymal stem cells of cirrhosis patients show insulin resistance and bioenergetic exhaustion
Authors: dhananajay Kumar, Deepanshu Maheshwari, Smriti Shubham, Nidhi Nautiyal, Sheetalnath Rooge, Lovkesh Anand, Ashish Vyas, Rekha Kumari, Shwetank Sharma, Rakhi Maiwall, Sujata Mohanty, Chhagan Bihari, Anupam Kumar, Shiv Kumar Sarin
Journal: Journal of Hepatology (2019)
Mobile Telephone Use and Reaction Time in Drivers With Glaucoma
Authors: Nara G. Ogata, Fábio B. Daga, Alessandro A. Jammal, Erwin R. Boer, Linda L. Hill, James M. Stringham, Remo Susanna, Felipe A. Medeiros
Journal: JAMA Network Open (2019)

Combining mobile telephone use with driving is not unusual. However, distracted driving limits driving performance because of limited capacity for persons to divide attention.To investigate the frequency of mobile telephone use while driving and to assess whether patients with glaucoma had a disproportionate decrease in driving performance while conversing on a mobile telephone compared with healthy participants.Cross-sectional study of surveys collected from 112 patients with glaucoma and 70 control participants investigating mobile telephone use while driving. A randomly selected subgroup of 37 patients with glaucoma and 28 controls drove in a driving simulator to investigate peripheral event detection performance during distracted driving at the Visual Performance Laboratory, Duke University, Durham, North Carolina. Data collection was performed from December 1, 2016, through April 30, 2017.Participants answered a survey and submitted to a driving simulation test with and without mobile telephone use.Survey answers were collected, and distracted driving performance, assessed by reaction time to peripheral stimuli, was analyzed.Of the 182 participants who answered the survey, the 112 participants with glaucoma included 56 women (50.0%) and had a mean (SD) age of 73.6 (9.6) years. The 70 controls included 49 women (70.0%) and had a mean (SD) age of 68.4 (10.9) years. When asked about mobile telephone use while driving, 30 patients with glaucoma (26.8%) admitted rarely using and 2 (1.8%) sometimes using it. In the control group, 20 participants (28.6%) admitted rarely using and 2 (2.9%) sometimes using the telephone while driving (P = .80). Reaction times to peripheral stimuli were significantly longer among patients with glaucoma compared with controls during mobile telephone use (median [interquartile range], 1.86 [1.42-2.29] seconds vs 1.14 [0.98-1.59] seconds; P = .02). Compared with driving performance while not using a mobile telephone, the mean (SD) increase of 0.85 (0.60) second in reaction time while conversing on the mobile telephone among patients with glaucoma was significantly greater than the mean (SD) increase of 0.68 (0.83) second for controls (P = .03).This study's findings indicate that patients with glaucoma use mobile telephones while driving as frequently as healthy participants. However, the findings also suggest that patients with glaucoma may experience a greater decline than healthy participants in their ability to detect peripheral events while driving when also talking on a mobile telephone. Patients with glaucoma should be informed that they may have a higher driving risk that may be worsened by distractions, such as mobile telephone use.
In-depth serum proteomics reveals biomarkers of psoriasis severity and response to traditional Chinese medicine
Authors: Meng Xu, Jingwen Deng, Kaikun Xu, Tiansheng Zhu, Ling Han, Yuhong Yan, Danni Yao, Hao Deng, Dan Wang, Yaoting Sun, Cheng Chang, Xiaomei Zhang, Jiayu Dai, Liang Yue, Qiushi Zhang, Xue Cai, Yi Zhu, Hu Duan, Yuan Liu, Dong Li, Yunping Zhu, Timothy R. D. J. Radstake, Deepak M.W. Balak, Danke Xu, Tiannan Guo, Chuanjian Lu, Xiaobo Yu
Journal: Theranostics (2019)

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.
Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis
Authors: Maren H. Harms, Henk R. van Buuren, Christophe Corpechot, Douglas Thorburn, Harry L.A. Janssen, Keith D. Lindor, Gideon M. Hirschfield, Albert Parés, Annarosa Floreani, Marlyn J. Mayo, Pietro Invernizzi, Pier Maria Battezzati, Frederik Nevens, Cyriel Y. Ponsioen, Andrew L. Mason, Kris V. Kowdley, Willem J. Lammers, Bettina E. Hansen, Adriaan J. van der Meer
Journal: Journal of Hepatology (2019)