tbuckley/cabot-search huggingface dataset:
Abstract 5651: Achieving simultaneous improvements in workflow and multiplexing in whole-slide tissue imaging
Authors: Michael Natan
Journal: Cancer Research (2018)

Abstract With very high spatial and biological complexity, tumor micro-environments present a significant characterization challenge, which is only heightened by the need to image entire sections of cancer tissue on many different samples. A variety of techniques offer very high levels of multiplexing, but always fail on either speed requirements (incredibly long times required to image a whole slide) or on compatibility issues (expensive, hard-to-operate CapEx not suitable for high-throughput CLIA operation). Ultivue has developed a platform reagent technology (InSituPlex™) that simultaneously enables whole- slide higher multiplexing by immunofluorescence AND complete compatibility with existing instrumentation. The InSituPlex technology comprises five key foundational elements. First, short unique DNA barcodes are covalently attached to each primary antibody (Ab). These conjugates are purified and functionally characterized in tissue for optimal staining specificity. Importantly, all of this work is done in advance by Ultivue. Second, tissue samples are stained in a single step. Third, all the DNA sequences attached to targets (via primary Ab binding) are simultaneously amplified, allowing for detection of less abundant markers e.g. PD-1, PDL-1 etc. Fourth, complementary DNA sequences each with different, covalently- attached fluorescent labels (“imager strands”) are simultaneously hybridized to the amplified DNA on the targets. All these wet chemistry steps are carried out in walkaway mode using commercially available auto-stainers. The samples are then imaged using a standard, whole-slide multi-color fluorescence imaging system. Finally, in an optional fifth step, the imager strands are gently removed via an enzymatic dehybridzation- with complete retention of antigenicity- to enable higher multiplexing via additional rounds of hybridization/imaging. The InSituPlex reagent technology offers many advantages for cancer research over current approaches: • the ability to detect 5, 10, or more targets simultaneously via whole-slide imaging on an each and every sample, with no loss in antigenicity; • the ability to leverage existing auto-stainers and existing fluorescent microscopes with Ultivue's reagent kits to carry out high-throughput analyses of multiple cancer biomarkers; and • the ability to design custom biomarker panels that leverage Ultivue's unique barcoding capability and infrastructure. This poster will elaborate on each step of the technology, and provide multiple examples of data acquired using different biomarker panels and different cancer tissue types. Citation Format: Michael Natan. Achieving simultaneous improvements in workflow and multiplexing in whole-slide tissue imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5651.
Abstract 14711: Circannual Pattern and TEMPerature-Related Incidence of Electrical STorm: The TEMPEST Study
Authors: Federico Guerra, Paolo Bonelli, Marco Flori, Laura Cipolletta, Corrado Carbucicchio, Maite Izquierdo, Edward Kozluk, Marmar Vaseghi, Kalyanam Shivkumar, Francesca Patani, Claudio Cupido, Salvatore Pala, Ricardo Luiz-Granell, Angel Ferrero, Claudio Tondo, Alessandro Capucci
Journal: Circulation (2016)

Introduction: The occurrence of ventricular tachyarrhythmias appears to follow circadian, daily, and seasonal distributions. Identifying potential temporal pattern could be even more important in patients experiencing electrical storm (ES), in which a cluster of ventricular tachycardias (VTs) or ventricular fibrillation (VFs), negatively affects short- and long-term survival. Hypothesis: ES incidence could be associated with the time of the year, time of the week, time of the day and short-term temperature variations. Methods: The Circannual pattern and TEMPerature-related incidence of Electrical Storm study (TEMPEST, # CRD42013003744) is a patient-level meta-analysis. Study selection criteria included: diagnosis of ES; absence of acute coronary syndrome as the arrhythmic trigger; ten or more patients included. At the end of the selection and collection processes, 5 centres had the dataset from their papers merged into the registry. Temperature data and sunrise and sunset hours were retrieved from Weather...
Evolving Paradigms in HIV Malignancies: Review of Ongoing Clinical Trials
Authors: Rachel A. Bender Ignacio, Lilie L. Lin, Lakshmi Rajdev, Elizabeth Chiao
Journal: Journal of the National Comprehensive Cancer Network (2018)

This review highlights current interventional clinical trials for HIV-associated malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic therapies; novel tumor-targeted and virally targeted therapies in both AIDS-defining and non–AIDS-defining cancers (NADC); and other screening or topical/ablative interventions. A search on ClinicalTrials.gov located 35 trials, including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials, 10 trials of therapies with tumor or viral molecular targets, and 7 trials evaluating screening interventions or topical or ablative therapies. Study drugs, mechanisms, and outcomes of interest, including future directions, are discussed. Targeted therapies and immunotherapies address not only the tumor but underlying viral oncogens, including possible benefits on HIV-specific immunologic control. The resulting science from the trials listed in this review will provide important translational breakthroughs for people living with HIV (PLWH) and cancer. We highlight disease-specific challenges that could be addressed in future studies, including testing the safety and efficacy of cutting-edge immunotherapy and targeted treatments used in the general cancer population, and improving gaps in knowledge and practice for cancer screening and its treatment, especially in low-resource regions. Additional important considerations include identification of novel therapies for virally mediated tumors that disproportionally present in PLWH, how to treat persons with HIVAM and advanced immunosuppression, and how to comanage both diseases in antiretroviral therapy–naïve persons and those receiving care in settings where supportive therapies for hematologic toxicities and infections are limited. Current and future clinical trials should address needs of both resource-replete and -limited regions, as well as cancers that are uncommon in or respond differently to HIV-negative populations (eg, Kaposi sarcoma or anal cancer), in addition to an increased focus on NADCs not traditionally linked with HIV, such as lung or gastrointestinal tumors.
Effects of Cavotricuspid Isthmus Ablation on Atrioventricular Node Electrophysiology in Patients With Typical Atrial Flutter
Authors: Ching-TaiTai, Chin-FengTsai, Ming-HsiungHsieh, Wei-ShiangLin, Yung-KuoLin, Shih-HuangLee, Wen-ChungYu, Yu-AnDing, Mau-SongChang, Shih-AnnChen
Journal: Circulation (2001)

Background The atrial musculature in the cavotricuspid isthmus is a part of posterior inputs to the AV node. In patients with typical atrial flutter, effects of radiofrequency ablation of this isthmus on AV node conduction are still unknown. Methods and Results This study included 16 patients with clinically documented typical atrial flutter. Group 1 had 8 patients without and group 2 had 8 patients with dual AV nodal pathway physiology. Electrical pacing from the interatrial septum and low right atrium was performed to evaluate antegrade AV node function before and after ablation of the cavotricuspid isthmus. In group 1, the AV node conduction properties were similar before and after ablation. In group 2, the AV node Wenckebach cycle length and maximal AH interval during low right atrium (356±58 versus 399±49 ms, P=0.008; 303±57 versus 376±50 ms, P=0.008) and interatrial septum (365±62 versus 393±59 ms, P=0.008; 324±52 versus 390±60 ms, P=0.008) pacing were significantly longer after ablation. Eliminatio...
Abstract LB-379: Targeted single-cell RNA expression profiling for cellular characterization of tumor microenvironment
Authors: Alex Chenchik, Michael Makhanov, Costa Frangou, Paul Diehl
Journal: Cancer Research (2018)

Abstract New rapid and robust transcriptome-based methods for cellular characterization of the tumor microenvironment and biomarker discovery are required to improve prognosis and treatment of cancer and other diseases. However, challenges with current approaches for the above applications include high sample requirements, poor sensitivity, low dynamic range, and limited throughput. To address these limitations, we have developed the DriverMap™ targeted RNA expression profiling assay using a genome-wide set of 19,000 validated primer pairs that leverages the sensitivity of multiplex RT-PCR with the throughput and digital readout depth of next-generation sequencing (NGS). Starting from just 10pg (single-cell) to 100ng (10,000 cells) of total RNA is sufficient to quantify over 5 orders of magnitude variation in gene expression levels with performance similar to conventional qRT-PCR. Further, the use of gene-specific primers enables direct analysis of total RNA isolate and obviates the need for globin and rRNA depletion from whole blood samples. And, using a subset of primers empirically selected from the DriverMap™ assay, we have developed a novel single-cell targeted RNA expression (scTRex) profiling assay compatible with conventional oligo dT-molecular indexing, single- cell barcoding strategies. In this study, we present the performance of the assay to analyze the level of immune cell infiltration in tumor samples, and identify active pathways in tumor, xenograft samples and cell lines treated with small molecules. Preliminary studies demonstrate the assay's unparalleled specificity and sensitivity resulting in better detection of low abundance mRNA transcripts as well as an improved cost-effectiveness for high-throughput clinical applications. Citation Format: Alex Chenchik, Michael Makhanov, Costa Frangou, Paul Diehl. Targeted single-cell RNA expression profiling for cellular characterization of tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-379.
Proinflammatory Stimuli Engage Brahma Related Gene 1 and Brahma in Endothelial Injury
Authors: FeiFang, DeweiChen, LimingYu, XinDai, YuyuYang, WenfangTian, XianCheng, HuihuiXu, XinyuWeng, MingmingFang, JiliangZhou, YuqiGao, QiChen, YongXu
Journal: Circulation Research (2013)

Rationale:Endothelial dysfunction inflicted by inflammation is found in a host of cardiovascular pathologies. One hallmark event in this process is the aggregation and adhesion of leukocyte to the vessel wall mediated by the upregulation of adhesion molecules (CAM) in endothelial cells at the transcriptional level. The epigenetic modulator(s) of CAM transactivation and its underlying pathophysiological relevance remain poorly defined. Objective:Our goal was to determine the involvement of Brahma related gene 1 (Brg1) and Brahma (Brm) in CAM transactivation and its relevance in the pathogenesis of atherosclerosis. Methods and Results:In the present study, we report that proinflammatory stimuli augmented the expression of Brg1 and Brm in vitro in cultured endothelial cells and in vivo in arteries isolated from rodents. Overexpression of Brg1 and Brm promoted while knockdown of Brg1 and Brm abrogated transactivation of adhesion molecules and leukocyte adhesion induced by inflammatory signals. Brg1 and Brm in...
Abstract 4924: Evaluation of the efficacy of curcumin and Y15 in platinum resistant ovarian cancer cells
Authors: Arkene S. Levy, Appu Rathinavelu, Nicole Coelho, Amanda Ramnot, Thanigaivelan Kanagasabai, Olena Bracho, Robert Smith
Journal: Cancer Research (2018)

Abstract Curcumin, a compound derived from turmeric (Curcuma longa), inhibits the proliferation of multiple cancer cell types, including ovarian, pulmonary, brain, and breast through various mechanisms. In advanced ovarian cancer, focal adhesion kinase (FAK), a tyrosine kinase, is overexpressed and contributes to platinum resistance. The compound Y15 (1, 2, 4, 5-benzene tetra amine tetrahydrochloride) inhibits FAK phosphorylation and subsequent activation. Therefore, in the present study we evaluated the combined cytotoxic efficacy of Curcumin and Y15 in platinum resistant OVCAR3 ovarian cancer cells. Cells were initially treated with concentrations of Y15 (10-100 μM), and curcumin (0-20µM) to determine IC10 values. Cells were subsequently treated with Y15 (20 μM) and curcumin (5 µM) alone and in combination. The cytotoxic profile of each treatment was assessed using the MTT assay. DNA fragmentation and poly ADP ribose polymerase (PARP) cleavage assays were performed to evaluate the mechanism of cell death. We further evaluated the expression of total FAK, phosphorylated FAK, p53, p21, and BAX in response to treatments using western blot. Y15 significantly increased the cytotoxic efficacy of curcumin when compared to the curcumin only treatment. Cell death by apoptosis was confirmed by PARP cleavage and the presence of DNA fragments in Y15, curcumin, and curcumin plus Y15 treatment groups. The curcumin plus Y15 combination significantly downregulated the expression of phosphorylated FAK when compared to the individual treatments and control. Reduced FAK phosphorylation also correlated with increased expression of P53, P21 and BAX in curcumin and Y15 treatment groups. These results indicate that Y15 significantly enhances the cytotoxic profile of curcumin in platinum resistant OVCAR-3 cells. This study is the first to report a FAK dependent cytotoxic mechanism of curcumin in ovarian cancer and in further work we will evaluate the signaling pathways involved. Citation Format: Arkene S. Levy, Appu Rathinavelu, Nicole Coelho, Amanda Ramnot, Thanigaivelan Kanagasabai, Olena Bracho, Robert Smith. Evaluation of the efficacy of curcumin and Y15 in platinum resistant ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4924.
Abstract 17659: The Impact of Routine HbA1c Screening on the Prevalence of Diabetes Mellitus and Outcomes in Patients Undergoing Percutaneous Coronary Intervention
Authors: Muhammad Abu Tailakh, Doron Zahger, Michael Friger, Aviel Sidi, Efrat Mazor, Victor Novack
Journal: Circulation (2014)

Introduction: The reported rate of Diabetes Mellitus (DM) in patients undergoing Percutaneous Coronary Intervention (PCI) is 30%-40%. In 2008, the International Expert Committee recommended diabetes diagnosis by HbA1c level ≥6.5%. Our aim was to determine the prevalence of previously undiagnosed DM defined by elevated HbA1c in patients undergoing PCI and its association with 1-year clinical outcomes. Methods: Consecutive patients undergoing PCI in a large tertiary teaching hospital were enrolled (2011-2013). HbA1c was measured before angiography. The primary outcome was 1-year Major Adverse Cardio- and Cerebrovascular Event (MACCE) defined as death, stroke, PCI or acute MI. Secondary outcomes included short term mortality. Results: 1313 patients were enrolled (795 with ACS). DM was previously known in 528 (40.2%) patients, 232 (17.7%) had Undiagnosed DM (UDM) based on the HbA1c ≥6.5% and 553 (42.1%) did not have diabetes (Non-DM). In patients with DM HbA1c was 8.0±1.8% as compared 7.6±1.4% in patients UDM (p=0.003). UDM patients were younger (64±11) compared to DM (69±11) and non-DM (64.5±13), p&lt;0.001. In-hospital mortality was 0.9%, 4% and 3.4% in non-DM, DM and UDM patients, respectively (p=0.004). One-year MACCE rates were 18%, 28%, and 19% in non-DM, DM, and UDM groups, respectively (p&lt;0.001). Multivariate analysis showed that compared to non-DM (reference), the DM and UDM groups had MACCE hazard ratios of 2.11 (p&lt;0.001) and 1.06 (p=0.55) adjusted for age, gender, smoking, previous ischemic heart disease and acute coronary syndrome. Conclusions: Pre-procedure HbA1c testing leads to the diagnosis of previously unknown DM in a large subgroup of patients undergoing PCI. These patients represent an intermediate group as their short term mortality resembles that of patients with DM while 1-year MACCE rates are similar to non-DM patients, possibly reflecting early detection and treatment. Our findings support routine screening for DM in all patients undergoing PCI.
Abstract P394: Opioid Use and Atrial Fibrillation: The Reasons for Geographic and Racial Differences in Stroke (regards) Study
Authors: WaqasQureshi, WesleyO'neal, MonikaSafford, PaulMunter, YuliaKhednova, SuzanneJudd, VirginiaHoward, GeorgeHoward, ElsayedSoliman
Journal: Circulation (2015)

Background: The use of opioids has been linked to adverse cardiovascular outcomes, suggesting a potential for an association with atrial fibrillation (AF). Conversely, opioid agonists have shown to reduce AF development in animals. It is unknown whether the use of opioids is associated with AF. Objective: The aim of this study was to examine the baseline association between prescription opioid use and AF in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. Methods: A total of 24,632 participants (mean age: 65 ± 9.4 years; 54% women; 40% blacks) were included in this analysis. Prescription use of opioids was ascertained by pill bottle review during the in-home study visit. AF was identified at baseline by the study electrocardiogram or self-reported history of a previous physician diagnosis. Logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) for the cross-sectional association between opioid use and AF. Results: A total of 1,887 (7.6%) part...
“No respite” for NHS as heatwave exacerbates pressure on services
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Latest NHS performance figures show that the NHS continues to struggle against key performance targets.1 NHS leaders said that this summer’s heatwave in the UK had offered “no respite” and had put added pressure on already overstretched services.

Emergency attendances —In July 2018, 1.4 million people attended an emergency department in England, the highest number in a summer month since …
Abstract 12063: High-risk Plaque Co-localizes With Low Endothelial Shear Stress and Expansive Remodeling in Human Coronary Arteries: <i>A 3D Optical Coherence Tomography Study</i>
Authors: Yiannis S Chatzizisis, Konstantinos Toutouzas, Andreas A Giannopoulos, Maria Riga, Antonios P Antoniadis, Dimitrios Mitsouras, Yusuke Fujinom, Vassilis G Koutkias, Grigorios Cheimariotis, Charalampos Doulaverakis, Ioannis Tsampoulatidis, Ioanna Chouvarda, Ioannis Kompatsiaris, Sunao Nakamura, Frank J Rybicki, Nicos Maglaveras, Dimitris Tousoulis, Charalambos Karvounis, George D Giannoglou
Journal: Circulation (2015)

Background: High risk plaque accounts for the majority of acute coronary events. Low endothelial shear stress (ESS) is a key factor of the natural history of atherosclerosis. The role of ESS in high risk plaque formation is not well studied in man. Hypothesis: To explore the association of low ESS with high risk plaque and to identify the ESS milieu and vascular remodeling response in high risk vs. non high risk plaque. Methods: 35 coronary arteries from 30 patients were 3D reconstructed with fusion of coronary angiography and optical coherence tomography (Fig A-D) . ESS was calculated in the 3D reconstructed arteries using computational fluid dynamics (Fig E) and classified into low, moderate and high in 3 mm long segments. In each segment: i) fibroatheromas were classified into high risk and non high risk based on fibrous cap thickness and lipid pool size ii) vascular remodeling was classified into constrictive, compensatory and expansive. Results: Fibroatheromas in low ESS segments had significantly thinner fibrous cap compared to high ESS segments (89±84 vs.138±83 μm, p&lt;0.05). Lipid pool size was comparable across all ESS categories. The majority of low ESS segments co-localized with high risk plaques (29 vs. 9%, p&lt;0.05), whereas the majority of high ESS co-localized with non high risk plaques (24 vs. 9%, p&lt;0.05, Fig F ). Compensatory and expansive remodeling was the predominant remodeling response in low ESS segments containing high risk plaques. In non-stenotic fibroatheromas (expansive or compensatory remodeling) low ESS was predominantly associated with high risk plaques (29 vs. 3%, p&lt;0.05) whereas high ESS was associated with non high risk plaques (Fig F) . Conclusions: Novel combined anatomic and functional imaging with 3D OCT showed that low ESS and non-constrictive remodeling are associated with high risk plaque in man. Further studies are needed to assess the role of ESS and vascular remodeling in high risk plaque rupture and precipitation of clinical outcomes.
Abstract 2467: Role of PCA3 in prostate cancer cell proliferation and progression
Authors: Bethanie Russel, Jiuhui Wang, Yuanqin Zhang, Daotai Nie
Journal: Cancer Research (2018)

Abstract Background PCA3 is a long non-coding RNA used as an important biomarker in early prostate-cancer diagnosis but its biological functions are not understood. The aim of the study is to investigate the potential role of PCA3 in prostate cancer (PCa) initiation, growth and progression. Methods Human genomic DNA was used as templates for cloning of PCA3 gene. Primers were designed and polymerase chain reactions were performed. The 3 exons of PCA3 were cloned and confirmed by sequencing. To determine the impact of PCA3 and its individual exon in PCa cell growth and survival, we over-expressed them respectively in PC-3 and DU145 cell lines via transduction with lentiviral vector. qPCR was performed to examine the expression level of PCA3. To investigate the effects of PCA3 on prostate cancer cells, cell proliferation assay was performed by using trepan blue staining. Colony formation assays were performed to measure the clonogenic capacity of the cells after PCA3 overexpression and treatments with docetaxel. Results and conclusions Sequencing of PCA3 gene amplified from human tumor cells did not find mutations when compared to RefSeq. We overexpressed PCA3 in prostate cancer cells and found that increased PCA3 expression did not have significant impacts on DU145 or PC-3 cell proliferation. However, PCA3 exon 3 did increase the clonogenic capacity of DU145 cells when compared to the controls. DU145 cells with increased PCA3 exon 3 also presented increased resistance to docetaxel. No significance was observed in clonogenic capacity in transduced PC-3 cells, but PCA3 increased the motility of PC-3 cells. Our studies suggest that PCA3 can modulate prostate cancer cell clonogenic capacity, docetaxel resistance, and motility. Further studies are ongoing to determine the mechanisms involved. Citation Format: Bethanie Russel, Jiuhui Wang, Yuanqin Zhang, Daotai Nie. Role of PCA3 in prostate cancer cell proliferation and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2467.