tbuckley/cabot-search huggingface dataset:
Targeted high-throughput sequencing for the routine diagnosis of somatic theranostic mutations on formalin-fixed, paraffin-embedded FFPE tumor samples: A prospective study of 3366 cancer samples.
Authors: Jean Mosser, Alexandra Lespagnol, Amyra Aliouat, Annick Mosser, Helena Gourdet, Gaelle Moron, Frederique Guenot, Cecile Chaplais, Marie de Tayrac
Journal: Journal of Clinical Oncology (2015)

e22187 Background: Improving of patient care relies on tumor genetic profiling that will guide treatment strategy. This implies the ability of parallel genotyping of a growing number of mutations. By providing an increase in sequencing throughput, NGS technology is suitable for routine implementation of such diagnostic in the near future. To address this challenge, we developed a robust end-to-end production and analysis workflow for routine molecular diagnosis of FFPE samples. Methods: A custom panel of 97 amplicons covering a 5.8 kb region was designed to detect mutations in 17 key cancer genes. We used an amplicon strategy workflow for library preparation including: Access Array System (Fluidigm) for targeted amplification, and MiSeq (Illumina) for deep sequencing. A pipeline dedicated to diagnosis was developed to automate the process of variant detection from the alignment of the genomic sequences to the detection and annotation of two types of genetic variations: single nucleotide variations (SNVs) and short insertions or deletions (indels). NGS data was obtained on 3366 patients (1598 NSCLC, 1447 colorectal cancers, 230 melanomas and 91 gliomas) and compared with reference technics pyrosequencing (PS) and allele-specific PCR (ARMS) used in routine. Results: Deep sequencing results in a minimum of 500X coverage for all amplicons, and detects 826 alterations, including 770 SNVs and 56 short indels. Among theses, 822 were also found with the reference methods. NGS lead to 3 false negative mutations due to poor DNA quality. Four false positive mutations detected only by NGS suggest that NGS can detect mutations bypassed by classical methods. Considering PS and ARMS as references, deep sequencing provides a 99,6% sensitivity and a 99,9% specificity. Conclusions: We demonstrate that our deep sequencing approach can be reliably implemented as a diagnostic test for routine detection of somatic mutations. Our strategy allows the simultaneous analysis of hotspot mutations in 17 key cancer genes for 48 samples in a single assay and thus improves the molecular diagnosis of tumors in a cost and time efficient manner.
THU-158-High efficacy of sofosbuvir and velpatasvir regardless of patients’ clinical characteristics
Authors: Vitor Hugo Martins, Giulia Troshina, Giulia Verzon, Michela Ciruolo, Felice Rizzi, Claudia Chialà, Ludovica Venezia, Pablo Cortegoso Valdivia, Stefano Rizza, Giorgio Maria Saracco, Alessia Ciancio
Journal: Journal of Hepatology (2019)
FRI-026-Long-term assessment of the effects of obeticholic acid in patients with primary biliary cholangitis on immune and inflammatory markers
Authors: Gideon Hirschfield, Frederik Nevens, Mitchell Shiffman, Joost Ph Drenth, Christopher Bowlus, Victor Manuel Vargas Blasco, Pietro Andreone, Alexander Liberman, Elizabeth Smoot Malecha, Leigh Macconell, Michael Trauner
Journal: Journal of Hepatology (2019)
Abstract 18165: Paroxysmal Atrial Fibrillation Risk Factors and Treatments: What is the Impact on Quality of Life?
Authors: Kathleen T Hickey, Robert R Sciacca, Angelo B Biviano, William Whang, Hasan Garan, Ashton P Frulla, Nicole R Hauser, Teresa C Riga, Paul Gonzalez, Daniel Y Wang
Journal: Circulation (2016)

Introduction: Paroxysmal Atrial Fibrillation (PAF), compounding cardiac risk factors and their treatments can impact quality of life (QoL). The aim of this study was to assess the impact of PAF tre...
Abstract 15121: Cigarette Taxes Have Greater Impact on Smoking Rates in Young Adults: An Assessment Using the Behavioral Risk Factor Surveillance System 2001-2015
Authors: Michael S Sharbaugh, Andrew D Althouse, Floyd W Thoma, Vince M Figueredo, Joon S Lee, Suresh R Mulukutla
Journal: Circulation (2017)

Introduction: We sought to determine if changes in state cigarette taxes are associated with declining smoking rates from 2001-2015, both in the overall U.S. population and within age-specific subg...
Genome-wide identification of cancer-specific alternative splicing in circRNA
Authors: Jing Feng, Ke Chen, Xin Dong, Xiaolong Xu, Yuxuan Jin, Xinyang Zhang, Wenbo Chen, Yujing Han, Lin Shao, Yang Gao, Chunjiang He
Journal: Molecular Cancer (2019)

Circular RNA (circRNA) is a group of RNA families generated by RNA circularization, which was discovered ubiquitously across different cancers. However, the internal structure of circRNA is difficult to determine due to alternative splicing that occurs in its exons and introns. Furthermore, cancer-specific alternative splicing of circRNA is less likely to be identified. Here, we proposed a de novo algorithm, CircSplice, that could identify internal alternative splicing in circRNA and compare differential circRNA splicing events between different conditions ( http://gb.whu.edu.cn/CircSplice or https://github.com/GeneFeng/CircSplice ). By applying CircSplice in clear cell renal cell carcinoma and bladder cancer, we detected 4498 and 2977 circRNA alternative splicing (circ-AS) events in the two datasets respectively and confirmed the expression of circ-AS events by RT-PCR. We further inspected the distributions and patterns of circ-AS in cancer and adjacent normal tissues. To further understand the potential functions of cancer-specific circ-AS, we classified those events into tumor suppressors and oncogenes and performed pathway enrichment analysis. This study is the first comprehensive view of cancer-specific circRNA alternative splicing, which could contribute significantly to regulation and functional research of circRNAs in cancers.
PS-015-Role of methylation-controlled J-protein, endogenous repressor of the mitochondrial respiratory chain, in cholestatic liver disease
Authors: Paula Iruzubieta, Lucía Barbier-Torres, Naroa Goikoetxea, Teresa Cardoso Delgado, David Fernández Ramos, Marta Varela-Rey, Virginia Gutiérrez de Juan, Pablo Fernández Tussy, Imanol Zubiete-Franco, Jorge Simón, Daniela Mestre Congregado, Fernando Lopitz Otsoa, Beatriz Gómez Santos, Xabier Buque, Marcos López-Hoyos, Patricia Apichueta, José M. Mato, Juan Anguita, Mercedes Rincón, Javier Crespo, María Luz Martínez-Chantar
Journal: Journal of Hepatology (2019)
Chemotherapy with immune-checkpoint inhibitors in first-line treatment metastatic NSCLC patients: Systematic review and literature-based meta-analysis
Authors: A. Addeo, G.L. Banna, G. Metro, M. Di Maio
Journal: Annals of Oncology (2019)

Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC), but little is known about the real benefit within the different PDL1 expression subgroups. Our aim was to estimate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhibitors plus chemotherapy versus chemotherapy alone, overall and in subgroups defined by PDL1 expression. Methods: This meta-analysis searched PubMed and checked references of articles to identify trials that combined checkpoint with chemotherapy versus chemotherapy in the first-line setting. For each trial included in this study, the trial name, year of publication or conference presentation, patients' clinic-pathological characteristics, type of chemotherapy, type of checkpoint inhibitor and PDL1 expression were extracted. Data collection took place from October 1th to October 24th, 2018. A random-effects model was applied. Results: Eight trials with advanced NSCLC were included in this meta-analysis. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, compared with chemotherapy in the ITT population (HR, 0.61; 95% CI, 0.61-0.66; P<.000001). OS was prolonged in the PDL1 0% group (HR, 0.78; 95% CI, 0.67-0.90; P<.0007) and in the PDL1 high (HR, 0.61; 95% CI, 0.48-0.78; P<.00001) but not in the PDL1 low (HR, 0.77; 95% CI, 0.55-0.107; P < 0.12). Chemotherapy plus pembrolizumab showed OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P<.00007)in low PD-L1 low, unlike atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P < 0.69). Checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P < 0.00001) across PDL1 subgroups. Conclusions: Checkpoint inhibitors plus chemotherapy compared to chemotherapy, are associated with prolonged OS and PFS in first-line therapy in NSCLC. In low PDL1 subgroup the benefit was statistically significant only in the pembrolizumab backbone trials. The findings of this meta-analysis could assist in the design and interpretation of future trials and in economic analyses. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: A. Addeo: Consulting role: MSD, Roche, Pfizer, Astrazeneca, BMS, Boehringer Ingelheim; Research grant: Boehringer Ingelheim; Travel grant: Roche, MSD. M. Di Maio: Honoraria for lectures in meeting, participation in Advisory boards: Astellas, Janssen. All other authors have declared no conflicts of interest.
TCTAP A-130 Accuracy and Safety of Newly Developed Optical-based FFR Device Compared to Conventional FFR Device
Authors: Akihiro Suzuki, Hiroaki Takashima, Yuki Saka, Katsuhisa Waseda, Hirohiko Ando, Yusuke Nakano, Shinichiro Sakurai, Masanobu Fujimoto, Hirofumi Ohashi, Akihito Tanaka, Hideki Ishii, Tetsuya Amano
Journal: Journal of the American College of Cardiology (2019)
Avid 68Ga-PSMA Uptake in Accessory Submandibular Salivary Gland
Authors: Wei Zhang, Li Zhang, Yanhong Zhao, Yue Chen
Journal: Clinical Nuclear Medicine (2019)

Abstract Accessory submandibular salivary gland (ASSG) is an extremely rare variation of the submandibular salivary gland. We reported a 65-year-old man with prostate cancer underwent 68 Ga-PSMA PET/CT for active surveillance. The images showed abnormal PSMA uptake adjacent to the submandibular salivary gland without abnormal activity distribution in the rest regions of the body. The lesion density was similar to that of the submandibular salivary gland. Pathological biopsy confirmed that it was an ASSG. Our case illustrates that ASSG is an addition benign cause of extraprostatic uptake of PSMA.
TCTAP C-136 Unexpected Complications During Transradial PCI
Authors: Md Saqif Shahriar, Mir Jamal Uddin, Sabina Hashem, Ashraf Ur Rahman, Fathima Aaysha Cader, Md Minhaj Arefin, Chayan Singha
Journal: Journal of the American College of Cardiology (2019)
Temperature-responsive biometamaterials for gastrointestinal applications
Authors: Sahab Babaee, Simo Pajovic, Ameya R. Kirtane, Jiuyun Shi, Ester Caffarel-Salvador, Kaitlyn Hess, Joy E. Collins, Siddartha Tamang, Aniket V. Wahane, Alison M. Hayward, Hormoz Mazdiyasni, Robert Langer, Giovanni Traverso
Journal: Science Translational Medicine (2019)

Temperature-responsive, reconfigurable metamaterials actuated by ingestion of warm water can be applied to the upper gastrointestinal tract.
Association between the EGFR or KRAS mutation status and the FDG-PET findings in surgically resected lung adenocarcinoma.
Authors: Kazuya Takamochi, Kaoru Mogushi, Kota Imashimizu, Mariko Fukui, Shiaki Oh, Masayoshi Itoh, Yoshihide Hayashizaki, Kenji Suzuki, Hideya Kawaji
Journal: Journal of Clinical Oncology (2015)

7535 Background: 18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on the glucose metabolism. The association between EGFR or KRAS mutations and the standardized uptake value (SUV) of 18F-FDG has not yet been fully elucidated. Methods: Correlations between the EGFR or KRAS mutation status and clinicopathological factors including SUVmax were statistically analyzed in 734 surgically resected lung adenocarcinoma patients. A cap analysis of gene expression (CAGE), a method to determine and quantify the transcription initiation activities of mRNA across the genome reflecting gene expression levels by determining the 5’ ends of capped RNA molecules using high-throughput sequencers, was done to examine the molecular basis between the SUVmax and mutations in 62 lung adenocarcinomas. Results: EGFR and KRAS mutations were detected in 334 (46%) and 83 (11%) of the 734 lung adenocarcinomas, respectively. Univariate analyses showed EGFR mutations to be more frequently observed in females, never-smokers, patients with normal CEA levels, tumors without lymph node involvement and blood vessel invasion, and tumors with lower SUVmax values. In multivariate analyses, the smoking status and the SUVmax were the significant predictors of EGFR mutations. In contrast, no relationship was seen between the KRAS mutation status and the SUVmax. Four genes associated with the glucose metabolism and five genes associated with the cell cycle showed a lower expression in the EGFR mutated tumors than the wild type tumors and a positive correlation with SUVmax. However, no such genes were found for KRAS mutations. Conclusions: Tumors with EGFR mutations show lower values of SUVmax than wild type ones.In contrast, no relationship was found between KRAS mutation and the SUVmax. These results suggest that tumors with EGFR mutations are less aggressive with likely lower levels of glucose metabolism.
SAT-306-Autotaxin is a valuable biomarker for predicting liver fibrosis in patients with non-alcoholic fatty liver disease
Authors: Yasushi Honda, Kento Imajo, Takashi Kobayashi, Takaomi Kessoku, Yuji Ogawa, Masato Yoneda, Satoru Saito, Atsushi Nakajima
Journal: Journal of Hepatology (2019)
FRI-456-MELD score is the only predictor for 30-day mortality in patients with ruptured hepatocellular carcinoma treated by emergent transarterial embolization
Authors: Ya-Ting Cheng, Wei Teng, Rachel Wen-Juei Jeng, Yi-Chung Hsieh, Kar-Wai Lui, Chien-Hao Huang, Wei-Ting Chen, Chien-Fu Hung, Chen-Chun Lin, Chun-yen Lin, Shi-Ming Lin, I-Shyan Sheen
Journal: Journal of Hepatology (2019)
When doctors and parents disagree: royal college issues advice on dealing with conflict
Authors: Abi Rimmer
Journal: BMJ (2019)

Disagreement between doctors and parents about a child’s treatment can usually be resolved by careful listening or early involvement of mediation services, says new advice from the Royal College of Paediatrics and Child Health (RCPCH).1

When this does not work, legal and ethical advice may be needed for the parties to act in the child’s best interests.

The advice on how to manage such disagreements over a child’s care has been issued after the high profile cases of Alfie Evans and Charlie Gard, babies born with untreatable conditions. Their cases prompted media campaigns, lengthy court battles, and threats from …
Recent developments and future directions in adult lower-grade gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus
Authors: David Schiff, Martin Van den Bent, Michael A Vogelbaum, Wolfgang Wick, C Ryan Miller, Martin Taphoorn, Whitney Pope, Paul D Brown, Michael Platten, Rakesh Jalali, Terri Armstrong, Patrick Y Wen
Journal: Neuro-Oncology (2019)

Abstract The finding that most grades II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and deletional analysis of cyclin-dependent kinase inhibitor 2A and 2B. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing, and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein.
PS-118-HCV eradication before or following curative management of HCC in patients with cirrhosis allows optimal tumour management and improves survival: The French multicentre prospective ANRS CO12 CirVir cohort experience
Authors: Pierre Nahon, Layese Richard, Cagnot Carole, Marcellin Patrick, Dominique Guyader, Pol Stanislas, Roudot Francoise, Etienne Audureau
Journal: Journal of Hepatology (2019)
EBV(LMP1)-induced metabolic reprogramming inhibits necroptosis through the hypermethylation of the <i>RIP3</i> promoter
Authors: Feng Shi, Min Zhou, Li Shang, Qianqian Du, Yueshuo Li, Longlong Xie, Xiaolan Liu, Min Tang, Xiangjian Luo, Jia Fan, Jian Zhou, Qiang Gao, ShuangJian Qiu, Weizhong Wu, Xin Zhang, Ann M. Bode, Ya Cao
Journal: Theranostics (2019)

EBV infection is a recognized epigenetic driver of carcinogenesis. We previously showed that EBV could protect cancer cells from TNF-induced necroptosis. This study aims to explore the epigenetic mechanisms allowing cancer cells with EBV infection to escape from RIP3-dependent necroptosis. Methods: Data from the TCGA database were used to evaluate the prognostic value of RIP3 promoter methylation and its expression. Western blotting, real-time PCR, and immunochemistry were conducted to investigate the relationship between LMP1 and RIP3 in cell lines and NPC tissues. BSP, MSP and hMeDIP assays were used to examine the methylation level. Induction of necroptosis was detected by cell viability assay, p-MLKL, and Sytox Green staining. Results: RIP3 promoter hypermethylation is an independent prognostic factor of poorer disease-free and overall survival in HNSCC patients, respectively. RIP3 is down-regulated in NPC (a subtype of HNSCC). EBV(LMP1) suppresses RIP3 expression by hypermethylation of the RIP3 promoter. RIP3 protein expression was inversely correlated with LMP1 expression in NPC tissues. Restoring RIP3 expression in EBV(LMP1)-positive cells inhibits xenograft tumor growth. The accumulation of fumarate and reduction of α-KG in EBV(LMP1)-positive cells led to RIP3 silencing due to the inactivation of TETs. Decreased FH activity caused fumarate accumulation, which might be associated with its acetylation. Incubating cells with fumarate protected NPC cells from TNF-induced necroptosis. Conclusion: These results demonstrate a pathway by which EBV(LMP1)-associated metabolite changes inhibited necroptosis signaling by DNA methylation, and shed light on the mechanism underlying EBV-related carcinogenesis, which may provide new options for cancer diagnosis and therapy.
FRI-154-Augmentation of HBV-specific CD4 T cell responses via combined 0X40 stimulation and PD-L1 blockade
Authors: Katharina Wild, Felix Jacobi, Maike Smits, Katharina Zoldan, Tobias Flecken, Julia Lang, Philipp Ehrenmann, Florian Emmerich, Maike Hofmann, Christoph Neumann-Haefelin, Robert Thimme, Tobias Böttler
Journal: Journal of Hepatology (2019)
False-Positive 68Ga-DOTATATE PET/CT in Active Chronic Prostatitis
Authors: Burcak Yilmaz, Hilal Serap Arslan, Cihan Gundogan, Mehmet Nuri Gunes, Tevfik Fikret Cermik
Journal: Clinical Nuclear Medicine (2019)

Abstract A 66-year-old man with neuroendocrine tumor originating from midgut was referred to 68 Ga-DOTATATE PET/CT imaging for restaging postoperatively. No suspicious uptake regarding residual primary tumoral involvement was seen. But there was diffuse high uptake in prostate gland suggestive of prostatitis or secondary primary tumoral lesion. Concurrent prostate-specific antigen level was 5.02 ng/mL (range, 0–4 ng/mL), C-reactive protein level was 8.25 mg/L (range, &lt;5 mg/L), and white blood cell count was 6.83 × 10 3 /μL (range, 3.9–10.9 × 10 3 /μL). Diagnosis of active chronic prostatitis was achieved by core biopsy, which is identified as potential cause for false-positive diffuse uptake on 68 Ga-DOTATATE PET/CT.
Improved neuropsychological outcomes following proton therapy relative to X-ray therapy for pediatric brain tumor patients
Authors: Jeffrey P Gross, Stephanie Powell, Frank Zelko, William Hartsell, Stewart Goldman, Jason Fangusaro, Rishi R Lulla, Natasha Pillay Smiley, John Han-Chih Chang, Vinai Gondi
Journal: Neuro-Oncology (2019)

Abstract Background Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT). Methods Pediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation—including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning—were identified. Multivariate analyses were performed to assess differences in neuropsychological outcomes and included tests for interaction between treatment cohort and follow-up time. Results Between 1998 and 2017, 125 patients with tumors located in the supratentorial (17.6%), midline (28.8%), or posterior fossa (53.6%) compartments received radiation and had posttreatment neuropsychological evaluation. Median age at treatment was 7.4 years. The PRT patient cohort had higher estimated SES and shorter median time from radiotherapy completion to last neuropsychological evaluation (6.7 vs 2.6 y, P &lt; 0.001). On multivariable analysis, PRT was associated with higher full-scale IQ (β = 10.6, P = 0.048) and processing speed (β = 14.4, P = 0.007) relative to XRT, with trend toward higher verbal IQ (β = 9.9, P = 0.06) and general adaptive functioning (β = 11.4, P = 0.07). Planned sensitivity analyses truncating follow-up interval in the XRT cohort re-demonstrated higher verbal IQ (P = 0.01) and IQ (P = 0.04) following PRT, with trend toward improved processing speed (P = 0.09). Conclusions PRT is associated with favorable outcomes for intelligence and processing speed. Combined with other strategies for treatment de-intensification, PRT may further reduce neuropsychological morbidity of brain tumor treatment.
Safety and Efficacy of Transcatheter Aortic Valve Replacement With Continuation of Oral Anticoagulation
Authors: Miriam Brinkert, Lukas S. Keller, Noriaki Moriyama, Florim Cuculi, Matthias Bossard, Dirk Lehnick, Richard Kobza, Mika Laine, Fabian Nietlispach, Stefan Toggweiler
Journal: Journal of the American College of Cardiology (2019)