tbuckley/cabot-search huggingface dataset:
Reliability of the detection of the mutation burden status by targeted next generation sequencing applying a large gene panel
Authors: N. Pfarr, M. Boxberg, K. Riedmann, M. Jesinghaus, B. Konukiewitz, H. Glimm, P.J. Jost, S. Fröhling, W. Weichert
Journal: Annals of Oncology (2018)

Background: In the emerging field biomarker analysis the need for testing of tumor mutation burden in routine diagnostic becomes more and more important. Currently most analysis is done by exome sequencing but regarding time for diagnosis and limitation of tissue material for testing the applicability of large gene panels becomes of great value. To test the feasibility of targeted next generation sequencing using formalin-fixed paraffin-embedded tissue for assessing tumor mutation burden statuswe applied the 1.95 Mb Illumina TSO500 panel covering an exonic region of about 1.24 Mb. Methods: A three-phase approach was applied: 1. Validation of the panel using DNA derived from 8 different cell lines (mutation high vs. mutation low). 2. Comparison of data from whole exome sequencing (mutation high vs. mutation low) vs.the TSO500 panel from 36 FFPE tumor samples. 3. Testing of ten samples with a) high PD-L1, or b) high MSI status or c) POLE mutation. Sequencing was performed on a NextSeq® system with the NextSeq® 500 hi-Output Kit v2 (300 cycles) and 40ng DNA as input. Data analysis was performed using a bioinformatics pipeline ("TSO500") provided by Illumina with a limit of detection of 5% allele frequency. Results: The mutation burden status of all validation samples (phase 1) were confirmed applying our NGS panel approach achieving a concordance of 100%. In phase 2 we were able to confirm the mutation burden status high or low derived from exome sequencing for all except for two cases achieving a concordance of 94% between the different approaches. In further testing a UDG pre-treatment of DNA samples will be performed to decrease the amount of fixation artefacts and therefore improve the quality of the tested samples. Analysis of the samples from phase 3 confirmed a high mutation status for the MSI high and the POLE mutated cases all revealing a mutation burden values whereas the PD-L1 cases showed only borderline values. Conclusions: We here show that data generated by targeted NGS data approaches can be used to determine the mutation burden status in tumor samples of different entities in high concordance with exome sequencing. Furthermore, additional genetic events (e.g. MSI) that may be clinically exploitable can be identified using a single assay. Legal entity responsible for the study: Nicole Pfarr. Funding: Illumina. Disclosure: N. Pfarr: Member of the immune oncology Consortium (Thermo Fisher Scientific). H. Glimm: Clinical studies: Pfizer, AstraZeneca; Honoraria and travel: Roche, Lilly, Amgen. S. Fröhling: Clinical studies: Pfizer, PharmaMar, AstraZeneca; Honoraria and travel: PharmaMar, Roche, Lilly, Amgen. W. Weichert: Advisory board and/or speakers bureau: Lilly, BMS, Merck/Sharpe, Dome, Novartis, Pfizer, Roche, AstraZeneca, Boehringer, Merck; Research funding: BMS, Roche, MSD. All other authors have declared no conflicts of interest.
Abstract 18889: The Prognostic Impact of Decreased Proportional Pulse Pressure in Heart Failure With Reduced Ejection Fraction
Authors: Masafumi Ono, Atsushi Mizuno, Syun Kohsaka, Ryoma Fukuoka, Nobuyuki Komiyama, Yasuyuki Shiraishi, Takashi Kohno, Yuji Nagatomo, Ayumi Goda, Tsutomu Yoshikawa
Journal: Circulation (2017)

Introduction: Proportional pulse pressure (PPP) is known as a simple index correlated with cardiac index (CI) especially in heart failure patients with reduced left ventricular function. Although P...
Abstract 20474: Comparative Efficacy of Angiotensin Converting Enzyme Inhibitor and Angiotensin Receptor Blocker for Patients With Acute Myocardial Infarction and Renal Dysfunction
Authors: Jumin Won, Young Joon Hong, Myung Ho Jeong, Hyung Ki Jeong, Young Jo Kim, Shung Chull Chae, Taek Jong Hong, In Whan Seong, Jei Keon Chae, Chong Jin Kim, Myeong Chan Cho, Seung-Woon Rha, Jang Ho Bae, Ki Bae Seung, Seung Jung Park
Journal: Circulation (2017)

Introduction: Angiotensin converting enzyme inhibitors (ACEi) reduce mortality in patients with acute myocardial infarction (AMI) and heart failure. Recent trials showed that angiotensin receptor b...
P103 Genomic Evolution Analysis Delineates Acquisition of Invasiveness in Pathological Subtypes of Early-stage Lung Adenocarcinoma
Authors: C. Zhang, Y. Chen, Y. Wang, B. Jiang, S. Dong, Q. Nie, J. Yang, X. Yang, Y. Wu, X. Zhang, W. Zhong
Journal: Journal of Thoracic Oncology (2018)
Immunofixation (IF) in Urine Is Really Necessary to Define Complete Remission in Multiple Myeloma (MM)? a Subanalysis from the Pethema/GEM2012MENOS65 Phase III Clinical Trial
Authors: Ana Jiménez Ubieto, Bruno Paiva, Joaquin Martínez-López, Laura Rosinol, Maria Teresa Cedena Romero, Maria Jose Calasanz, Noemi Puig, Ramon Garcia-Sanz, Norma C. Gutierrez, Maria Luisa Martin-Ramos, Albert Oriol, José Gonzalez Medina, Rafael Alonso Fernandez, Jesús Blanchard, Rafael Rios, Jesús Martín, Rafael Martinez Martinez, Josep Sarra, Miguel-Teodoro Hernández, Javier De La Rubia, Isabel Krsnik, Jose Maria Moraleda, Luis Palomera, Maria-Victoria Mateos, Jesús F San-Miguel, Joan Bladé, Juan-José Lahuerta
Journal: Blood (2018)
Compared Abilities of Endoscopic Techniques to Increase Colon Adenoma Detection Rates: A Network Meta-analysis
Authors: Antonio Facciorusso, Konstantinos Triantafyllou, Mohammad Hassan Murad, Larry J. Prokop, Georgios Tziatzios, Nicola Muscatiello, Siddharth Singh
Journal: Clinical Gastroenterology and Hepatology (2018)
Potential Harms of HIPAA
Authors: Scott Mintzer
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Antipsychotics, Excess Deaths, and Paradoxes of Child Psychiatry
Authors: Barbara Geller
Journal: JAMA Psychiatry (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Differential Expression of Inducible Caspase-9 (iC9) in Allogeneic T Cells Allows Selective Depletion of Activated T Cells Following Exposure to Rimiducid and Permits In Vivo Allodepletion
Authors: Xiaoou Zhou, An Lu, Kelly L Sharp, Margie Harris, Madhavi Anumula, J. Bayle, David M. Spencer, Aaron Foster, Joanne Shaw
Journal: Blood (2018)
Retraction: HMGA Proteins Up-regulate <i>CCNB2</i> Gene in Mouse and Human Pituitary Adenomas
Authors: Ivana De Martino, Rosa Visone, Anne Wierinckx, Dario Palmieri, Angelo Ferraro, Paolo Cappabianca, Gennaro Chiappetta, Floriana Forzati, Gaetano Lombardi, Annamaria Colao, Jacqueline Trouillas, Monica Fedele, Alfredo Fusco
Journal: Cancer Research (2018)

[This article][1] ([1][2]) has been retracted at the request of the editors. The editors were made aware of concerns regarding potential manipulation of data in the article. An internal review by the editors determined that multiple duplicated electrophoretic mobility shift assay–free probe bands
Abstract O.05: The Incidence and Outcome of Kawasaki Shock Syndrome:2003-2013
Authors: Sara K Sexson Tejtel, Andrea A Ramirez, Thomas Seery, Amy Liou, Debra Canter, Marietta DeGuzman, Caroly A Altman
Journal: Circulation (2015)

Kawasaki disease (KD) is the leading cause of acquired heart disease in children with a subset presenting in shock. We sought to describe the incidence and outcomes of KD shock in the US. Methods: The Pediatric Health Information Systems (PHIS), 1/2004-12/2013, dataset including all hospitalizations at 44 of the largest freestanding children’s hospitals in the US was used. We assumed KD shock patients were admitted to the ICU. Results: KD admissions included 16,417 patients, 1,179 requiring ICU care, KD shock, with an annual incidence of 8 - 13%, Figure 1. Among KD shock admissions (versus non-ICU KD), the length of stay (10 vs 4 days, P&lt;0.001) and mortality (10 vs 1 death) is higher in the shock group. The rate of coronary artery (CA) changes during initial admission for KD shock was higher than non-shock, Figure 2 (P&lt;0.001). Conclusions: KD shock may not be an uncommon presentation given 8-13% of KD admissions required ICU care. KD shock patients are more likely to have complications including coronary artery changes, mechanical ventilation, ECMO, and longer hospitalizations than non-ICU admissions.
Abstract 19615: Combined Heart-Kidney Transplantation Acceptable in Older Recipients: Outcomes From the UNOS Registry
Authors: Sadia Dimbil, Ryan Levine, Jignesh Patel, Elizabeth Passano, Lawrence Czer, Jon A Kobashigawa
Journal: Circulation (2017)

Introduction: Combined heart-kidney transplantation (HKTx) has proven to be an acceptable option in a subset of heart transplant patients with end-stage renal failure. It has been demonstrated that older transplant recipients have worse post-transplant outcome. We sought to evaluate whether older HKTx recipients (> 60 years) have increased mortality and worse post-transplant kidney function compared to younger patients (≤ 60 years) who undergo HKTx. Methods: Between 1989 and 2016 we identified 1207 HKTx patients from the United Network for Organ Sharing (UNOS) database. We stratified by age of the recipient (≤ 60 years, n=870 vs > 60 years, n=337) and by age of the donor ( 50 years). As older organs are usually placed in older recipients, we also assessed the demographics of all groups. Endpoints of this study included renal function in terms of creatinine and glomerular filtration rate (GFR) at 12 months after transplant and 1-year survival. With respect to survival, UNOS re...
Abstract 15770: Plasma cBIN1 Based Heart Failure Index (HFI) Identifies Patients With HFpEF and Prognosticates Future Hospitalizations
Authors: Andriana P Nikolova, Tara C Hitzeman, Rachel Baum, Bing Xu, Sosse Agvanian, Yu Xie, Dael Geft, David Chang, Jaime Moriguchi, Antoine Hage, Babak Azarbal, Lawrence Czer, Michelle Kittleson, Jignesh Patel, Jon Kobashigawa, Michele Hamilton, TingTing Hong, Robin Shaw
Journal: Circulation (2017)

Introduction: Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for half of the HF burden worldwide. Cardiac bridging integrator 1 (cBIN1) is a t-tubule protein essential for calcium signaling which correlates with cardiac health. Hypothesis: We hypothesize that a Heart Failure Index (HFI) based on plasma cBIN1 concentration is a diagnostic and prognostic biomarker in HFpEF patients. Methods: The HFpEF cohort comprises 52 stable patients with documented prior episodes of HF and with preserved left ventricular ejection fraction (LVEF≥50%). The control cohort includes 104 age and sex matched healthy volunteers. cBIN1 concentration was determined by a novel cBIN1-specific ELISA test. Patient characteristics were obtained per chart review and patients were followed for 1 year post cBIN1 assay. HFI is computed as the log of the normalized reciprocal of cBIN1. Results: Median HFI is 0 in the healthy population and is increased in the HFpEF population to 1.8 (p<0.0001). Receiver operator chara...
Abstract 10944: The Optimal Definition of Contrast-Induced Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions
Authors: Jessica Parsh, Milan Seth, Carlo Briguori, Paul Grossman, Richard Solomon, Hitinder Gurm
Journal: Circulation (2015)

Background: Multiple definitions exist for contrast induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions (PCI). It is unknown which definition is best associated with adverse events and whether this association is stable across patients with various degrees of baseline renal function. Hypothesis: We hypothesized that commonly used CI-AKI definitions would not be stable in risk prediction for mortality across the spectrum of renal function. Further, we sought to identify the optimal CI-AKI definition which would be both highly predictive of mortality and stable in its association regardless of baseline renal function. Methods: We applied logistic regression models to multiple current CI-AKI definitions to examine the impact of baseline renal function on a candidate CI-AKI definition’s correlation with the adverse outcome of mortality. We then utilized Likelihood ratios to examine candidate definitions and identify those where association with mortality remained constant regardless of baseline serum creatinine (SCr). These definitions were then assessed for specificity, sensitivity and positive and negative predictive values to identify an optimal definition. Results: Our study cohort comprised of 119,554 patients who underwent PCI in the state of Michigan between 2010-2014. Most commonly used definitions were not associated with mortality in a constant fashion across baseline renal function. Of the 266 candidate definitions examined, 16 definition’s association with mortality was not significantly altered by baseline SCr. CI-AKI defined as an absolute increase of SCr ≥ 0.3 mg/dl and a relative SCr increase ≥ 50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for mortality. Conclusions: We identified the optimal definition for CI-AKI to be an absolute increase in SCr ≥ 0.3 mg/dl and a relative SCr increase ≥ 50%. Further work is needed to validate this definition in independent studies, in other clinical settings, and to establish its utility for clinical trials and quality improvement efforts.
Virological analysis of fatal influenza cases in the United Kingdom during the early wave of influenza in winter 2010/11
Authors: J Ellis, M Galiano, R Pebody, A Lackenby, CI Thompson, A Bermingham, E McLean, H Zhao, S Bolotin, O Dar, J  M Watson, M Zambon
Journal: Eurosurveillance (2011)

The 2010/11 winter influenza season is underway in the United Kingdom, with co-circulation of influenza A(H1N1)2009 (antigenically similar to the current 2010/11 vaccine strain), influenza B (mainly B/Victoria/2/87 lineage, similar to the 2010/11 vaccine strain) and a few sporadic influenza A(H3N2) viruses. Clinical influenza activity has been increasing. Severe illness, resulting in hospitalisation and deaths, has occurred in children and young adults and has predominantly been associated with influenza A(H1N1)2009, but also influenza B viruses.
OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer
Authors: Jing Li, Dongdong Cheng, Miaoxin Zhu, Huajian Yu, Zhen Pan, Lei Liu, Qin Geng, Hongyu Pan, Mingxia Yan, Ming Yao
Journal: Theranostics (2018)

Increasing evidence has confirmed that deubiquitinating enzymes play an important role in lung cancer progression. In the current study, we investigated the expression profile of deubiquitinating enzymes in non-small cell lung cancer (NSCLC) tissues and identified OTUB2 as an upregulated deubiquitinating enzyme. The role of OTUB2 in NSCLC is unknown. Methods: Quantitative, real-time PCR and Western blot were used to detect OTUB2 and U2AF2 expression in NSCLC tissues. The correlations between OTUB2 and U2AF2 expression and clinicopathologic features were then analyzed. We used In vitro Cell Counting Kit-8 (CCK-8) , colony formation , and trans-well invasion assays to investigate the function of OTUB2 and U2AF2 in tumorigenesis. The regulation of glycolysis by OTUB2 and U2AF2 was assessed by determining the extracellular acid ratio, glucose consumption, and lactate production. The mechanism of OTUB2 was explored through co-immunoprecipitation and mass spectrometry analyses. A xenograft model was also used to study the tumorigenesis role of OTUB2 In vivo. Results: OTUB2 expression was significantly upregulated in primary NSCLC tissues and greatly associated with metastasis, advanced tumor stages, poor survival, and recurrence. In NSCLC cell lines, OTUB2 promoted cell growth, colony formation, migration, and invasive activities. Mechanistic investigations showed that OTUB2 stimulated the Warburg effect and induced the activation of the serine/threonine kinase/mechanistic target of rapamycin kinase (AKT/mTOR) pathway in different NSCLC cells. More importantly, OTUB2 promoted NSCLC progression, which was largely dependent on the direct binding to and deubiquitination of U2AF2, at least in NSCLC cells. U2AF2 expression was also significantly upregulated in primary NSCLC tissues and dramatically associated with metastasis, advanced tumor stages, poor survival, and recurrence. Importantly, a positive correlation between the protein expression of OTUB2 and U2AF2 in NSCLC tissues was found. In vivo experiments indicated that OTUB2 promoted xenograft tumor growth of NSCLC cell. In addition, our results suggest that high expression of OTUB2, U2AF2 and PGK1 is significantly associated with worse prognosis in NSCLC patients. Conclusion: Taken together, the present study provides the first evidence that OTUB2 acts as a pivotal driver in NSCLC tumorigenesis by stabilizing U2AF2 and activating the AKT/mTOR pathway and the Warburg effect. It may serve as a new potential prognostic indicator and therapeutic target in NSCLC.
A SNP germinal signature for predicting checkpoint inhibitor treatment outcome
Authors: G. Milano, S. Refae, J. Gal, N. Ebran, J. Otto, S. Shell, R. Everts, E. Chamorey, E. Saada-Bouzid
Journal: Annals of Oncology (2018)

Background: Cumulated clinical experience with checkpoint inhibitors (CPIs) points to a strong need for the identification of predictive biomarkers. Surprisingly, the potential role of the host has not been advocated so far. We developed a custom designed panel of single nucleotide polymorphisms (SNPs) from genes potentially implicated in the response to CPIs. Methods: We studied 94 patients treated in Centre Antoine Lacassagne (Nice, France) with CPI (anti PD-1/PD-L1). High-throughput genotyping of germinal DNA was performed by MassARRAY ImmunoCarta (AGENA Bioscience®) using a custom-panel of 173 SNPs across 90 selected genes (minor allelic frequency ≥5% in the Caucasian population). All tested SNPs were in Hardy-Weinberg equilibrium, and linkage disequilibrium analyses were performed (r2>0.8). A Ridge-penalized logistic regression with 5-fold cross validation was used for the SNP identification to predict objective response (complete or partial response) to treatment. Results: Median age of patients was 68 (range: 32-85), 67% were male, 51% had non-small cell lung carcinoma (NSCLC), 14% had head and neck squamous cell carcinoma (HNSCC), 15% had renal cell carcinoma (RCC), 13% had melanoma and 7% had another cancer type. Median follow-up was 16.3 months (95%CI: 12.5-18.3). The following SNPs' decreasing intrinsic weight according to response were selected by the multivariate modeling approach (CCR2: rs1799864, FAS: rs2234767, CD3G: rs3753058, CTLA4: rs5742909, CCL2: rs13900, TNXB: rs12153855, Il1RN: rs419598, PD1: rs11568821, IL17A: rs2275913, IL12B: rs3212227, TLR3: rs7668666, CXCR3: rs2280964, IL10: rs1800871, IL6: rs2069837, TRAF3: rs7145509, VEGFR3: rs307821). In the training set, the accuracy was 0.87 (95%CI: 0.76-0.95; p < 0.001) associated with a sensitivity and a specificity of 0.90 and 0.83, respectively, with a ROC curve AUC at 0.93 (95%CI: 0.87-0.99). In the validation set, the accuracy decreased to 0.71 (95%CI: 0.52-0.85; p < 0.02) associated with a sensitivity and a specificity of 0.82 and 0.60, respectively, and with a ROC curve AUC of 0.85 (95%CI: 0.72-0.98). Conclusions: These preliminary results point to the feasibility of a signature based on host characteristics for predicting response to CPI. Legal entity responsible for the study: Centre Antoine Lacassagne, Nice, France. Funding: Has not received any funding. Disclosure: G. Milano: Paid scientific consultant: Agena Bioscience. S. Shell, R. Everts: Employee of Agena Bioscience. All other authors have declared no conflicts of interest.
A letter to the editor on “Anterior Perineal PlanE for ultra-low Anterior Resection of the rectum (APPEAR) technique: A systematic review”. The APPEAR procedure is a sphincter-saving transsphincteric rectal resection technique, and the ischioanal fossa should not be considered as “The rectal no man's land”
Authors: Ali Naki Yücesoy
Journal: International Journal of Surgery (2018)
Abstract 14776: Predictors of “Visual-functional Mismatch” in Contemporary Practice -the Characteristics Associating With Mismatch Between Angiographic Stenosis and Hybrid IFR-FFR Strategy
Authors: Yuta Morioka, Hiroyuki Arashi, Junichi Yamaguch, Hiromu Kadowaki, Kazuki Tanaka, Ryosuke Itani, Hisao Otsuki, Kensuke Shimazaki, Shintaro Haruki, Masashi Nakao, Kazuho Kamishima, Kentaro Jujo, Yuichiro Minami, Hiroshi Ogawa, Nobuhisa Hagiwara
Journal: Circulation (2016)

Background: A “hybrid Instantaneous wave-free ratio (IFR) and fractional flow reserve (FFR) strategy” are increasing to evaluate functional severity of coronary intermediate stenosis in clinical se...