tbuckley/cabot-search huggingface dataset:
Prognostic significance of Cyclin D1 (CCND1) amplification in adenocarcinoma of the esophagus
Authors: Uta Reichelt, Maria Tsourlakis, Alexander Quaas, Bjorn-Christian Link, Jussuf Kaifi, Paulus Schurr, Stephanie Gros, Emre Yekebas, Andreas Marx, Ronald Simon, Jakob Izbicki, Guido Sauter
Journal: Cancer Research (2007)

1957  Introduction:  Cyclin D1 (CCND1) overexpression has been frequently reported in esophageal cancer. In other tumor entities, including pancreatic cancer, breast cancer, bladder and colon cancer CCND1 overexpression has been linked to gene amplification. The aim of our study was to analyze CCND1 copy number alteration in a large set of esophageal cancers with clinical follow up data.  Materials and Methods:  A total of 279 esophageal cancer samples on a tissue microarray (TMA), including 121 adenocarcinomas (ADC) and 158 squamous cell cancers (SQCC) and 141 matched metastases were analyzed for CCND1 gene alteration by means of fluorescence in situ hybridization (FISH). Amplification was defined as presence of at least two times more gene signals than centromer 11 signals.  Results:  Amplification was typically high level with more than 10 gene copies per tumor cell and was strikingly more frequent in squamous cell cancer (85/158, 54%) as compared to adenocarcinoma (14/121, 12%, P  Conclusions:  In conclusion, our data suggest that CCND1 amplification is of major clinical impact in esophageal cancer. This has not been reported for squamous cell cancer from other localizations. Squamous cell cancer of the esophagus is characterized by a molecular pathway involving CCND1 amplification. The overall adverse prognosis of squamous cell cancer of the esophagus might be directly linked to CCND1, since presence of amplification was linked to reduced survival also in adenocarcinoma of the esophagus.
Abstract 2572: Integrated viral sequences in esophageal cancer tissue
Authors: Victoria A. Patten, Lamech Mwaphaga, Christopher G. Mathew, Denver T. Hendricks, M. Iqbal Parker
Journal: Cancer Research (2019)

Abstract The human genome exhibits a significant degree of invasion by viral genomes. During the course of evolution, several RNA and DNA viruses have become integrated into the vertebrate genome and there is no reason to believe that the process has ended. Integrated viral DNA may account for as much as 10% of the human genome and it is very likely that they may act as carcinogens by altering normal cellular gene expression. In this study we have compared the viral DNA sequences present in normal and tumor tissues from esophageal squamous cell carcinoma (ESCC) samples. DNA was extracted from paired normal and tumor biopsies and subjected to whole genome sequencing. Raw data run folders were converted to FASTQ files and progressed through a QC pipeline. Normal and tumor data sets were then blasted and aligned against an extensive viral sequence database using specialized DRAGEN software, so that all integrated viral DNA fragment sequences were identified. The identified viral sequences were then compared between the paired normal and tumor samples. Using this approach, a large number of viral DNA sequences were identified; these included human papilloma viruses, Herpes simplex viruses, adenoviruses and Hepatitis C viruses. Furthermore, some unexpected viruses of interest were also identified. These include the Autographa Californica Nucleopolyhedrovirus, the Emiliana Huxleyi virus 86, the Gryllus bimaculatus nudivirus and the Trichodysplasia spinulosa-associated polyomavirus, present in different tumour DNA samples. Amplification and rearrangements of endogenous retroviruses such as the Human Endogenous Retrovirus K113 were also observed. Endogenous retroviruses (ERV) can serve as long-lasting viral reservoirs and provide evidence for the coexistence between retroviruses and their hosts over many generations. Defective ERVs can also recombine to affect the expression of adjacent genes. It has been proposed that integrated viral sequences may play a possible role in the etiology and promotion of diseases such as cancer, thus targeted studies of specific viral sequences may elucidate the mechanisms of gene disruption and may ultimately lead to the development of more effective therapeutic interventions. Note: This abstract was not presented at the meeting. Citation Format: Victoria A. Patten, Lamech Mwaphaga, Christopher G. Mathew, Denver T. Hendricks, M. Iqbal Parker. Integrated viral sequences in esophageal cancer tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2572.
Angioplasty with versus without routine stent placement for Budd-Chiari syndrome: a randomised controlled trial
Authors: Qiuhe Wang, Kai Li, Chuangye He, Xulong Yuan, Bohan Luo, Xingshun Qi, Wengang Guo, Wei Bai, Tianlei Yu, Jiahao Fan, Zhengyu Wang, Jie Yuan, Xiaomei Li, Ying Zhu, Na Han, Jing Niu, Yong Lv, Lei Liu, Jing Li, Shihao Tang, Shuai Guo, Enxing Wang, Dongdong Xia, Zhexuan Wang, Hongwei Cai, Jianhong Wang, Zhanxin Yin, Jielai Xia, Daiming Fan, Guohong Han
Journal: The Lancet. Gastroenterology & hepatology (2019)
Abstract 19348: Efficacy of Cryoballoon Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation
Authors: Emily Guhl, Donald Siddoway, Evan Adelstein, Samir Saba, Andrew Voigt, Sandeep K Jain
Journal: Circulation (2015)

Introduction: Cryoballoon pulmonary vein isolation (PVI) has emerged as an alternative to radiofrequency PVI for the treatment of paroxysmal atrial fibrillation (AF). The optimal ablation strategy for patients with persistent AF is unclear, as data on Cryoballoon PVI alone are limited. Methods: We analyzed a prospective registry of consecutive patients with persistent AF who underwent Cryoballoon PVI at a single center between 2011 and 2014. Patients were assessed for AF recurrence (including any atrial arrhythmia) after a 3 month blanking period at 6 months, 1 year, 2 years, and as needed for symptoms post PVI. Recurrence was based on typical symptoms or ECG/ event monitor evidence of AF. Kaplan-Meier analysis was used to estimate AF-free survival. Results: The 69 patients who underwent Cryoballoon PVI were aged 59 ± 8 years, 86% male, 54% HTN, had a CHADS2-VASC score 1.6 ± 1.2, and had a LA dimension 4.5 ± 0.6 cm. The AF recurrence-free rate at 1-year post-procedure was 59%. Overall, AF-free survival was 50% at the mean follow-up of 607 days. In comparing patients with persistent AF duration &lt;1 year vs. &gt;1 year, there was a trend toward greater AF recurrence-free rates in the &lt;1 year group (66% vs 55%, p=0.09) Conclusions: Cryoballoon PVI appears to be an effective initial strategy in treating persistent AF, with an AF recurrence-free rate of 59% at 1 year.
Limiting Access to Firearms as a Suicide Prevention Strategy Among Adults
Authors: Joseph A. Simonetti, Ali Rowhani-Rahbar
Journal: JAMA Network Open (2019)

Catherine L. Dempsey, PhD; David M. Benedek, MD; Kelly L. Zuromski, PhD; Charlotte Riggs-Donovan, MS; Tsz Hin H. Ng, MPH; Matthew K. Nock, PhD; Ronald C. Kessler, PhD; Robert J. Ursano, MD
Abstract 15361: Self-reported Overwhelmingness is Independently Associated With Worst Performance on Advanced Cardiac Life Support Training Course Practical Examination
Authors: Raphael A Oliveira, Eliane Soares, Fernando Zampieri, Daniel Azevedo, Heberth Miotto, Maria Aparecida Braga
Journal: Circulation (2015)

Background: It remains controversial whether acute mental stress negatively influences provider performance during Advanced Cardiac Life Support (ACLS) courses. The aim of this study was to evaluate the influence of self-reported acute stress measurements and socio-demographic features on provider performance on ACLS practical exams. Methods: At total of 326 consecutive attendees of ACLS courses were included in a prospective observational study performed by Sociedade Mineira de Terapia Intensiva (SOMITI) training centre, Brazil. Self-reported measures (stress related to the instructor and evaluation, felling overwhelmed and a combination of evaluation-related stress and felling overwhelmed known as the stress/overload index) were provided after attendees completed their practical examinations. We performed multivariate and automated conditional inference tree analyses to appraise the factors that influence provider performance. Poor performance was defined as not passing the practical exam. Results: Thirty-six providers showed poor performance on the practical evaluation. Failing the practical examination was associated with both felling overwhelmed (OR: 1.63 [95% CI: 1.37-1.93], p&lt;0.001) and the stress/overload index (OR: 1.77 [95% CI: 1.37-2.29], p&lt;0.001). Both variables were the most prominent factors associated with poor performance according to conditional inference tree analysis. However, stress related to the evaluation was not independently associated with non-approval. Multivariate analysis revealed that increased age, a lower percentage of ACLS materials studied before the course, stress related to the instructor and occupation as a nurse were also independently associated with poor performance. Conclusion: Self-reported felling overwhelmed was robustly associated with poor performance on the ACLS course practical examinations.
Abstract 16644: Interstage Clinical Outcomes and Resource Utilization Among Babies With Single Ventricle: Results of A Randomized Cross-over Study Comparing Standard of Care (Notebook) to Tablet PC-Based Monitoring
Authors: Girish Shirali, Lori Erickson, Kathy Goggin, Jonathan Apperson, Michael Bingler, Dawn Tucker, David Williams, Andrea Bradley-Ewing, Vincent Staggs, Amy Lay, Leslie Rabbitt, Richard Stroup
Journal: Circulation (2015)

Interstage outcomes for babies with single ventricle remain suboptimal. We have developed a tablet PC-based platform (CHAMP) for remote monitoring. This provides immediate access to data and instant alerts to the team. This study evaluates the caregiver experience with CHAMP, and its impact on interstage mortality, morbidity and resource utilization. Methods: All neonates with single ventricle who were discharged from 5/2014 to 5/2015 were prospectively enrolled. For 1 month after discharge, they were all monitored using a notebook. They were randomized to receive CHAMP at either 1 or 2 months post discharge. A month after randomization, caregivers had to choose either the notebook or CHAMP for the remainder of the inter-stage period. Charts were reviewed for mortality, unplanned readmissions and hospital charges. Caregiver experience was assessed through an exit survey. Results: We enrolled 24 babies (Norwood, n=11; BT shunt, n=9; no stage I at discharge (balanced circulation), n=3; hybrid, n=1). They were interstage for 3143 days. There was no interstage mortality in either group. While using CHAMP, families transmitted data on 77% of days. Resource utilization is summarized in the Table. CHAMP instant alerts and scheduled daily alerts led to 10 readmissions for issues that were not recognized by caregivers (low saturations (n=6) and poor feeding / weight gain (n=4). When given the option after randomization, 23 of 24 families chose CHAMP. At the end of monitoring, 23 completed an exit survey; when asked what form of monitoring they would choose if they had to do this over, 19 (82%) stated they would choose CHAMP, 3 would choose either, and 1 would choose the notebook. Conclusions: CHAMP monitoring was associated with significant decreases in unplanned readmission days, ICU days and hospital charges. CHAMP was well-accepted by caregivers, and would appear to facilitate outpatient care for the fragile population of interstage babies with single ventricle.
Abstract P244: Participation in a Community-based, Family-focused Lifestyle Intervention Improves the Home Food Environment: Athletes for Life Preliminary Findings
Authors: Sonia Vega-López, Emily Ghan, Michael Todd, Meg Bruening, Noe C Crespo
Journal: Circulation (2016)

It is known that availability of food in the home influences dietary behaviors; however, few studies have assessed the effects of lifestyle behavioral interventions on the home food environment (HFE). We hypothesized that participation in Athletes for Life (AFL), a family-oriented lifestyle intervention for cardiometabolic disease prevention, would result in favorable changes in the home food environment of families with children aged 6-11 years. AFL is a 12-week community-based, family-focused behavioral intervention delivered at a community center located in an ethnically-diverse, underserved community within a Southwestern metropolitan area. Participants attend 90-minute sessions, twice per week. For children, AFL includes diverse activities aimed at improving fitness and sport skills. Parents participate in a physical activity session for 45 minutes followed by a 45-minute behavior change program focusing on strategies for diet improvement through increasing fruit and vegetable consumption and reducing sugar intake. Parent-child dyads (n=33) were randomized to an immediate AFL intervention or a wait-list control group. Of those, 26 consented to a home visit to assess the HFE and were included in this analysis (intervention n=13; control n=13). The HFE was assessed in both groups at baseline and again after 12 weeks using a modified version of the Home Food Inventory that focused on home availability and variety (measured as number of different items) of fruits, vegetables, and sugar-containing foods including sugar-sweetened beverages, prepared desserts, candy, and breakfast cereals. Intervention effects on home food availability were assessed using Poisson mixed model regressions controlling for days since the last food-shopping trip and household size. At baseline, intervention and control households had comparable home food environments. Relative to the control group, the intervention households had statistically greater increases in the number of vegetable items (+3.88±0.85 items vs. +0.08±0.63 items; p Time*Group =0.015) and WIC-approved breakfast cereal items (1.16±0.31 items vs. 0.00±0.28 items; p Time*Group =0.033). Changes related to home availability of fruit, prepared desserts, sugar sweetened beverages, candy, and non WIC-approved breakfast cereals were small and of comparable magnitude between groups (n.s.). These results suggest that AFL was successful in eliciting small but significant changes in the HFE, which could positively influence dietary intake among participants. Future assessments of how home food availability affects dietary intake and cardiometabolic disease risk are warranted.
Abstract 1669: Full length transcriptome sequencing of melanoma cell line complements long read sequencing assessment of genomic rearrangements
Authors: Elizabeth Tseng, Brendan Galvin, Ting Hon, Wigard P. Kloosterman, Meredith Ashby
Journal: Cancer Research (2019)

Abstract Transcriptome sequencing has proven to be an important tool for understanding the biological changes in cancer genomes including the consequences of structural rearrangements. Short read sequencing has been the method of choice, as the high throughput at low cost allows for transcript quantitation and the detection of even rare transcripts. However, the reads are generally too short to reconstruct complete isoforms. Conversely, long-read approaches can provide unambiguous full-length isoforms, but lower throughput has complicated quantitation and high RNA input requirements has made working with cancer samples challenging. Recently, the COLO 829 cell line was sequenced to 50-fold coverage with PacBio SMRT Sequencing. To validate and extend the findings from this effort, we have generated long-read transcriptome data using an updated PacBio Iso-Seq method, the results of which will be shared at the AACR 2019 General Meeting. With this complimentary transcriptome data, we demonstrate how recent innovations in the PacBio Iso-Seq method sample preparation and sequencing chemistry have made long-read sequencing of cancer transcriptomes more practical. In particular, library preparation has been simplified and throughput has increased. The improved protocol has reduced sample prep time from several days to one day while reducing the sample input requirements ten-fold. In addition, the incorporation of unique molecular identifier (UMI) tags into the workflow has improved the bioinformatics analysis. Yield has also increased, with v3 sequencing chemistry typically delivering &amp;gt; 30 Gb per SMRT Cell 1M. By integrating long and short read data, we demonstrate that the Iso-Seq method is a practical tool for annotating cancer genomes with high-quality transcript information. Citation Format: Elizabeth Tseng, Brendan Galvin, Ting Hon, Wigard P. Kloosterman, Meredith Ashby. Full length transcriptome sequencing of melanoma cell line complements long read sequencing assessment of genomic rearrangements [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1669.
Abstract 4783: Highly efficient, non-viral precision genome engineering for the generation of personalized neoepitope-specific adoptive T cell therapies
Authors: Kyle Jacoby, Robert Moot, William Lu, Diana Nguyen, Barbara Sennino, Andrew Conroy, Bhamini Purandare, Adam J. Litterman, Fabrizia Urbinati, Susan P. Foy, Theresa Hunter, Albert Tai, Michael T. Bethune, Songming Peng, Olivier Dalmas, Alex Franzusoff, Stefanie J. Mandl
Journal: Cancer Research (2019)

Abstract Methods used to engineer cells for adoptive cell therapies (ACT) utilizing receptors that are constant across many patients (CAR or shared Ag TCRs) typically rely on Lenti-, retro-, or adeno-associated virus to deliver specificity-altering sequences to T cells. However, for personalized therapies such as the generation of neoepitope-specific TCR T cell therapies, use of viral vectors is not feasible due to long manufacturing timelines and prohibitive per-patient costs. PACT Pharma has developed a highly efficient, DNA-mediated (non-viral) proprietary precision genome engineering approach to engineer neoepitope-specific primary human T cells. This method can be widely utilized to generate T cells at research scale, as well as for ex vivo manufacturing. Briefly, genomes of individual primary human CD8 and CD4 T cells are engineered with site-specific nucleases in a single-step transfection process to yield efficient, targeted replacement of the endogenous TCR with the therapeutic neoTCR sequences. In this way, the expression of the endogenous TCR is abolished ensuring natural expression and regulation of the inserted neoTCR. The precision of neoTCR-T cell genome engineering was evaluated by Targeted Locus Amplification (TLA) for off-target integration hot spots or translocations, and by next generation sequencing based off-target cleavage assays and found to lack evidence of unintended outcomes. Engineered neoepitope-specific T cells are highly functional as demonstrated by antigen-specific proliferation, killing and cytokine production. Phenotype and detailed functional characterization of PACTs neoTCR-P1 T cells were performed and are described in a separate abstract. PACT’s precision genome engineering approach enables highly efficient generation of bespoke NeoTCR T cells for personalized adoptive cell therapy for patients with solid tumors. Furthermore, PACT precision genome engineering method is not restricted to the use in T cells and has also been applied successfully to other primary cell types, including natural killer and hematopoietic stem cells. Citation Format: Kyle Jacoby, Robert Moot, William Lu, Diana Nguyen, Barbara Sennino, Andrew Conroy, Bhamini Purandare, Adam J. Litterman, Fabrizia Urbinati, Susan P. Foy, Theresa Hunter, Albert Tai, Michael T. Bethune, Songming Peng, Olivier Dalmas, Alex Franzusoff, Stefanie J. Mandl. Highly efficient, non-viral precision genome engineering for the generation of personalized neoepitope-specific adoptive T cell therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4783.
Abstract 9997: Utilizing a Collaborative Learning Model to Decrease Length of Postoperative Ventilation Following Infant Heart Surgery
Authors: William T Mahle, Susan Nicolson, Lara S Shekerdemian, Michael G Gaies, Madolin K Witte, Eva K Lee, Michelle Goldsworthy, Paul Stark, Kristin M Burns, Marc A Scheurer, David S Cooper, Ravi Thiagarajan, Ben Sivarajan, Danielle Hollenbeck-Pringle, Steven Colan
Journal: Circulation (2015)

Introduction: Collaborative learning utilizes shared experience and expertise to rapidly disseminate knowledge across systems. We employed this strategy to reduce the duration of mechanical ventilation following infant heart surgery. Hypothesis: A collaborative learning derived clinical practice guideline (CPG) will result in a significant increase in the rate of early extubation (EE) following surgical repair of tetralogy of Fallot (TOF) or isolated coarctation (Coarct) in infants. Methods: A collaborative learning initiative that included site visits was employed at five centers (active sites) in the Pediatric Heart Network (PHN). Participants developed a CPG to achieve EE (within 6 hours of surgery) for infants following 2 index operations: 1) repair of isolated Coarct and 2) repair of TOF (30-365 days). EE rates were calculated at the five active sites during the 12 months before and after CPG implementation, and at five other centers in the PHN not participating in collaborative learning or using the CPG (control sites). A differences analysis was performed to compare changes in EE after CPG implementation. Results: Among the five active sites, there were 322 subjects that met eligibility for the CPG (163 pre- and 159 post-implementation). Among the five control centers, there were 259 subjects that would meet eligibility for the CPG (120 pre- and 139 post-implementation). With CPG implementation the rate of EE increased by 44.8% among active sites, from 28.8% to 73.6% (p&lt;0.001). No change in the rate of EE was found in the control sites 11.7% to 13.7% (p=0.58). At active sites, there was no change in the rate of reintubation within 48 hours (3.1% v 3.1%, p=0.97). At active sites there was no statistically significant impact on median intensive care unit (3.0 days pre- vs. 2.9 post-implementation, p=0.6) or total postoperative length of stay (PLOS)(6 days pre- vs. 5 post-implementation, p=0.5) with CPG implementation. Conclusions: A collaborative learning strategy designed to shorten postoperative mechanical ventilation led to a significant increase in the rates of EE with no change in the rate of reintubation. The EE CPG did not significantly change intensive care or total PLOS.