tbuckley/cabot-search huggingface dataset:
Abstract 5311: Integrated approaches for design of precision cancer immunotherapies: Selection of Class I and Class II T cell neo-epitopes and removal of Treg epitopes
Authors: Guilhem Richard, Lenny Moise, Matthew Ardito, Frances Terry, Gad Berdugo, William Martin, Anne De Groot
Journal: Cancer Research (2018)

Abstract Next-generation sequencing has opened the door to precision cancer therapies targeting mutations expressed by tumor cells. However, most neo-epitopes selected by traditional T cell epitope prediction algorithms prove to be non-immunogenic. Poor predictive performance may partially be due to inclusion of mutated epitopes cross-conserved with self-epitopes recognized by the T cell receptor of regulatory (Treg), anergic or deleted T cells. Vaccination with self-epitopes can lead to weak effector responses, active immune suppression, and toxicity due to immune-mediated adverse effects. We have developed Ancer, an advanced cancer T cell epitope identification and characterization tool, that streamlines the selection of Class I and Class II T cell neo-epitopes. Ancer leverages EpiMatrix and JanusMatrix, state-of-the-art predictive algorithms that have been extensively validated in prospective vaccine studies for infectious diseases [Moise et al., Hum. Vaccines Immunother 2015; Wada et al., Sci. Rep. 2017]. Distinctive features of Ancer are its ability to accurately predict Class II HLA ligands with EpiMatrix and its 82% positive predictive value, as estimated in previous prospective studies. Additionally, the application of JanusMatrix allows for the prioritization of neo-epitopes with reduced potential for Treg induction, that is responsible for diminished efficacy of current cancer therapies. We validated Ancer's predictive accuracy using datasets of HLA-bound peptides detected by mass spectrometry, which are independent of training sequence data used in model development. Analysis of sequences from Abelin et al., Immunity 2017 shows a 96% agreement between Ancer predictions and peptides eluted from common Class I HLAs, while only 86% of these sequences are accurately predicted by NetMHC or NetMHCpan. An additional retrospective analysis of a cancer immunogenicity study [Strønen et al., Science 2016] demonstrates that Ancer selects immunogenic neo-epitopes with 72% accuracy, as compared to 21% accuracy when using public prediction tools. These results demonstrate that Ancer may focus epitope candidate selection on higher value sequences than conventional algorithms. Class I and Class II neo-epitopes with low Treg activation potential may then be used to support the development of safer and more effective vaccines. Citation Format: Guilhem Richard, Lenny Moise, Matthew Ardito, Frances Terry, Gad Berdugo, William Martin, Anne De Groot. Integrated approaches for design of precision cancer immunotherapies: Selection of Class I and Class II T cell neo-epitopes and removal of Treg epitopes [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 5311.
Abstract P089: Pre-eclampsia and Risk of Subsequent Hypertension: In an American Indian Population
Authors: Lyle G Best, Laramie Lunday, Elisha Webster, James R Beal
Journal: Circulation (2016)

Background and Objectives: Preeclampsia (PE) is a pregnancy-specific disorder that affects 2-8% of all pregnancies and as many as 60,000 annual maternal mortalities globally. A number of proposed pathophysiologic mechanisms relate to similar factors implicated in cardiovascular disease, such as endothelial dysfunction, inflammation, insulin resistance and impaired renal regulation. Pre-eclampsia has been associated with subsequent hypertension, cardiovascular disease and related mortality in later life. Methods: The 3 most recent blood pressures, body mass index (BMI) and use of hypertensive medications were recorded from electronic medical records of routine clinic visits for 130 cases and 289 controls previously identified and carefully characterized for a study of the etiology and complications of PE. Comparison between case and control groups was made using the student t test for continuous variables and chi-square testing for discrete variables. Linear regression analysis was used to evaluate the effects of risk factors on subsequent systolic and diastolic blood pressure (SBP and DBP respectively). Results: Follow-up measurements occurred a mean of 13.11 years (range 3.6 to 36.7 years) post PE pregnancy. Cases were of similar age (35.9 vs 36.1 years, p=0.82); but with significantly higher BMI (34.1 vs 31.6, p&lt;0.002), systolic (127.2 vs 121.3 mm Hg, p&lt;0.001 and diastolic (76.2 vs 72.6 mm Hg, p&lt;0.001) blood pressure, and more likely to be using hypertensive medications (35/130, 27% vs 25/289, 9%, p&lt;0.001). Linear regression showed significant and independent association between BMI (SBP β=0.47, DBP β=0.29), age (SBP β=0.19, DBP β=0.14), previous history of PE (SBP β=4.47, DBP β=2.71) and current systolic and diastolic blood pressure (all p values &lt;0.002). Analysis of the quartile with follow-up of less than 7.19 years also shows independent association of prior PE with both SBP (β=6.54, p&lt;0.006) and DBP (β=4.96, p&lt;0.001). Discussion and Conclusions: PE appears to confer risk of subsequent hypertension on American Indian women after a period of at least 13 years. This risk is independent of additional risk factors such as increased BMI and age. The risk is apparent soon after the affected pregnancy and there are undoubtedly cases where the hypertension of PE fails to resolve post partum.
Abstract 3724: 5-FU-loaded Nucleoside Nanoparticles for Therapeutic Efficiency of Oral Cancer by various administrations
Authors: HUI FENG, Hang ZHAO, Ning Ji, Jing Li, Zhiyong Wang, lu jiang, Qianming Chen
Journal: Cancer Research (2018)

Abstract Drug delivery systems are designed to improve bioavailability, reduce degradation, and alleviate the side effect of the loaded drugs. Here, we reported the development of a novel monomeric self-assembled nucleoside nanoparticle (SNNP) into an efficient drug delivery system in such field. Initially, we used a L-configurational pyrimido[4,5-d]pyrimidine nucleoside building nano-bundles and then found its high biocompatibility and low toxicity in vitro and in vivo. Afterwards, the stability in blood circulation and the distribution of 5-FU in OSCC tissues was remarkably increased by the loading with SNNP. Most importantly, 5-FU-SNNP markedly retarded the in vivo growth of OSCC xenografts in mouse models compared with free 5-FU and SNNP by intratumoral, intraperitoneal and intravenous injection, respectively. It was worth mentioning that, SNNP can even reduce the toxic side effects of 5-FU using intraperitoneal injection on OSCC xenograft mouse model. Furthermore, the superior in vivo antitumor efficacy of 5-FU-SNNP compared with free 5-FU and SNNP was related to inhibit cell proliferation and promote cell apoptosis by TUNEL and immunohistochemistry analyses. These findings indicated that when loaded with 5-FU loaded with SNNP has better antineoplastic efficacy using various administrations and lower side-effects, suggesting that this new type of SNNP has a high hope to be a promising candidate nanoparticle-delivery strategy for cancer therapy clinically in the future. References Hang Zhao, Hui Feng, Dongjuan Liu, Jiang Liu, Ning Ji, Fangman Chen, Xiaobo Luo, Yu Zhou, Hongxia Dan, Xin Zeng, Jing Li, Congkui Sun, Jinyu Meng, Xiaojie Ju, Min Zhou, Hanshuo Yang, Longjiang Li, Xinhua Liang, Liangyin Chu, Lu Jiang, Yang He, and Qianming Chen. Self-Assembling Monomeric Nucleoside Molecular Nanoparticles Loaded with 5-FU Enhancing Therapeutic Efficacy against Oral Cancer. ACS nano. 2015; 9(10): 9638 - 9651. The authors gratefully acknowledge support from the National Natural Science Foundation of China (81520108009, 81500860,81700988). Citation Format: HUI FENG, Hang ZHAO, Ning Ji, Jing Li, Zhiyong Wang, lu jiang, Qianming Chen. 5-FU-loaded Nucleoside Nanoparticles for Therapeutic Efficiency of Oral Cancer by various administrations [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 3724.
Abstract 13989: Detection of Micro Intimal Tear at a Very Early Stage in Patients With Acute Aortic Intramural Hematoma
Authors: Masaki Nakashima, Shuichiro Kaji, Ryosuke Murai, Yasuhiro Sasaki, Mitsuhiko Ota, Kitae Kim, Takafumi Yamane, Takeshi Kitai, Atsushi Kobori, Natsuhiko Ehara, Makoto Kinoshita, Yutaka Furukawa
Journal: Circulation (2016)

Background: Although rupture of the vasa vasorum is thought to be the main cause of acute aortic intramural hematoma (IMH), previous studies have suggested the existence of micro intimal tear at the onset, which supported a common pathophysiologic mechanism of aortic dissection (AD) and IMH. A better understanding of the pathophysiology of IMH may lead to successful identification of high-risk patients and appropriate management. The purpose of this study was to investigate the prevalence and clinical outcome of micro intimal tear detected by multi-detector computed tomography (MDCT) in patients with IMH at a very early stage. Methods and Result: We retrospectively analyzed 50 patients with IMH who underwent 64-row MDCT at admission: 34 patients underwent MDCT within 3 hours (early scan group) and 16 patients more than 3 hours after the onset (late scan group). Micro intimal tear was defined as continuity disruption of the inner layer of thrombosed false lumen with tiny inflow of contrast medium, which suggested small flow communication. Localized contrast pooling in aortic wall, which is considered as a pseudoaneurysm of branch artery, was not regarded as micro intimal tear and excluded from the analysis. In early scan group, 18 (52%) patients had 27 micro intimal tears. Of these, 12 tears were located in aortic arch, 2 in proximal descending aorta (PD), 1 in mid descending aorta (MD), 9 in distal descending aorta (DD) and 3 in abdominal aorta (AA). In late scan group, 5 (31%) patients had 6 micro intimal tears; 1 in arch, 4 in DD and 1 in AA. Micro intimal tear observed in aortic arch was significantly more frequent (12/34) in early scan group than late scan group (1/16, p=0.03). During initial hospitalization, progression of micro intimal tears was observed in 11 of 18 patients (61%) in early group and 4 of 5 patients (80%) in late group (p=0.41). On the other hand, 2 micro intimal tears observed in arch regressed in early scan group. Conclusion: Early MDCT scan within 3 hours after the onset detected micro intimal tear in a considerable portion of patients with IMH, most frequently in aortic arch. These findings may suggest common pathophysiologic mechanism of AD and IMH.
Multiple Subcutaneous Nodules as Initial Presentation of Diffuse Large B-cell Non-Hodgkin Lymphoma (DLBCL) Detected by PET/CT
Authors: Guohua Shen, Ying Kou, Bin Liu, Anren Kuang
Journal: Clinical Nuclear Medicine (2018)

Subcutaneous tissue as a manifestation of generalized disease is commonly involved in lymphomas. However, only skin involvement without other sites of extracutaneous disease was rarely presented, especially in diffuse large B-cell lymphoma (DLBCL). Herein, we reported an unusual case of primary cutaneous DLBCL, solely presenting with multiple subcutaneous nodules in the abdomen and back, and these nodules showed increased FDG uptake on PET/CT images. PET/CT is very helpful for diagnosing primary cutaneous DLBCL.
Idiopathic Ventricular Fibrillation Induced With Vagal Activity in Patients Without Obvious Heart Disease
Authors: HiroshiKasanuki, SatoshiOhnishi, MasatoOhtuka, NaokiMatsuda, TakashiNirei, ReikoIsogai, MorioShoda, YukariToyoshima, SaichiHosoda
Journal: Circulation (1997)

Background Recently, idiopathic ventricular fibrillation (VF) has gained much attention. Although several subgroups have been described, its pathogenesis, mechanism, treatment, and prognosis remain unknown. Methods and Results We studied six cases of idiopathic VF with transient late r′ waves and ST elevation (late r′/ST elevation) in leads V1 through V3. Late r′/ST elevation was augmented before and after VF episodes. Signal-averaged ECGs showed late potentials even when no late r′/ST elevation occurred. During late r′, a conduction delay was observed by use of body-surface maps at the anterior wall and outflow tract of the right ventricle without inhomogeneity of the repolarization phase. There was a decrease or total disappearance of late r′/ST elevation with isoproterenol, atropine, and exercise stress testing and induction or exacerbation with propranolol, edrophonium, and hyperventilation. VF was induced by programmed electrical stimulation in all cases but two, in which it was induced only after ed...
Type 1 diabetes: earlier onset is linked to cardiovascular complications and reduced lifespan
Authors: Susan Mayor
Journal: BMJ (2018)

Developing type 1 diabetes at a younger age is associated with a higher risk of cardiovascular complications and a lower lifespan than later onset, a Swedish observational cohort study has shown.1

“Although the relative risk of cardiovascular disease is increased after an early diabetes diagnosis, the absolute risk is low,” said Araz Rawshani, study coauthor, from the University of Gothenburg in Sweden.

“However, age at disease onset appears to be an important determinant of survival as well as cardiovascular outcomes in early adulthood, warranting consideration of earlier treatment with cardioprotective drugs,” he added.

Current guidelines recommend aggressive management of cardiovascular risk factors in people with type 1 diabetes, particularly in those aged over 40 or with evidence of microvascular complications. But even those whose risk factors …
Regional variation limits applications of healthy gut microbiome reference ranges and disease models
Authors: Yan He, Wei Wu, Hui-Min Zheng, Pan Li, Daniel McDonald, Hua-Fang Sheng, Mu-Xuan Chen, Zi-Hui Chen, Gui-Yuan Ji, Zhong-Dai-Xi Zheng, Prabhakar Mujagond, Xiao-Jiao Chen, Zu-Hua Rong, Peng Chen, Li-Yi Lyu, Xian Wang, Chong-Bin Wu, Nan Yu, Yan-Jun Xu, Jia Yin, Jeroen Raes, Rob Knight, Wen-Jun Ma, Hong-Wei Zhou
Journal: Nature Medicine (2018)
Abstract 2505: Baicalein reverses chronic stress-induced ovarian cancer promotion through GABA receptors
Authors: Ke Li, Yu Kang, Yinhua Yu
Journal: Cancer Research (2018)

Abstract Studies suggest that chronic stress accelerate the progression of ovarian cancer, and the promotion effects can be abrogated by β-blockers. However, β-blockers should be assessed and tailored to each cancer patient as they will exert toxic effects in overdose. Baicalein, a widely used Chinese herbal medicine, identified as a new type of anticancer drug with an obvious function of anti-anxiety in animal experiments and whose mechanism may be mediated by GABA receptors. The focus of the current study was to determine whether baicalein could block the effects of chronic stress on tumor growth and investigate the underlying mechanism that relates to GABA receptors. Two kinds of ovarian cancer cell lines (OVCAR-8 and CAOV-3) were selected to be investigated in the inhibitory effect of baicalein on cancer cells. Cell CCK-8 assay, wound healing assay, transwell assay and flow cytometry were used for in vitro experiments. Chronic stress was induced by a restrained stress model in nude mice carrying xenografts in the presence and absence of treatment with baicalein. Xenograft sizes and weight were measured after 4 weeks. Norepinephrine was measured by HPLC and GABA was measured by immunoassays in blood and tumor tissues. Expression of GABA receptors in the xenografts was analyzed by real-time quantitative PCR, western blotting and immunohistochemistry (IHC). Our results showed that ovarian cancer cell lines exhibited significant promotion in the presence of NE concentrations of 10Μm and baicalein concentrations of 10μM could reverse its effects by Cell CCK-8 assay and wound healing assay. Daily restraint stress resulted in significantly increased tumor growth in tumor model of ovarian cancer in nude mice. And this increase was completely blocked with daily baicalein treatment. Chronic stress attenuated expression of GABA receptors in vivo and in vitro; conversely, baicalein increased expression of GABA receptors. Overall, our data suggest that baicalein stimulated GABA receptors activation to reduce tumor growth in ovarian cancer. Considering the stimulatory effects of chronic stress on cancer growth, our study implicates baicalein as a potential medicine for blocking the deleterious effects of chronic stress. Citation Format: Ke Li, Yu Kang, Yinhua Yu. Baicalein reverses chronic stress-induced ovarian cancer promotion through GABA receptors [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 2505.
Incidence and Clinical Consequences of Atrial Fibrillation Within 1 Year of First-Time Isolated Coronary Bypass Surgery
Authors: MaqsoodElahi, LeonidasHadjinikolaou, ManuelGaliñanes
Journal: Circulation (2003)

Background— Atrial fibrillation (AF) is the commonest complication during cardiac surgery, however, the long-term prevalence of AF following surgery and its clinical consequences remain unclear. Patients and Methods— To investigate this, 877 consecutive patients undergoing first time CABG were followed for 1 year. Rhythm disturbances were diagnosed from serial ECGs and documented notes. The arrhythmia was treated medically and/or by cardioversion. Results— Out of 877, 17 patients (1.9%) died in the hospital and out of the remaining 860 patients 844 (98.1%) had a complete 1-year follow-up. Patients were divided according to their age: Group I (50 to 59 years), Group II (60 to 69 years) and Group III (70 to 79 years). The prevalence of AF in the general population was taken from the Framingham Heart Study. Patients in groups I and II had a higher incidence of AF before the operation than the general population (1.5% versus 0.4% and 3.1% versus 1.6%, respectively, P<0.05) and also higher incidence of AF at t...
Abstract 938: Detection of actionable mutations in plasma cfDNA samples from patients with non-small cell lung carcinoma using a novel amplicon-based Firefly NGS assay
Authors: Lin Wang, Li Weng, Xiao Chen, Min Li, Qiaomei Guo, Wenjun Yu, Tobias Wittkop, Hongyan Wang, Malek Fahem, Shengrong Lin, Grace Q. Zhao, Jiatao Lou
Journal: Cancer Research (2018)

Abstract Background: Detection of EGFR, KRAS and BRAF mutations can help guide cancer treatment for non-small cell lung cancer (NSCLC) patients. To identify an easy to use, accurate, multiplex molecular diagnostic assay, we evaluated the performance of a novel next-generation sequencing (NGS)-based cell-free DNA (cfDNA) assay, Firefly assay, which employs a concatemer-based noise suppression mechanism with an amplicon workflow. Methods: Performance of amplicon based Firefly assay, with a panel covering EGFR, BRAF, and KRAS mutations designed for targeted therapy selection of NSCLC was first evaluated using a cfDNA reference standard and blank control samples. This panel was then used to analyze plasma cfDNA samples from 134 NSCLC cancer patients and 50 non-cancerous controls, and results were compared with tumor tissue ARMS and cfDNA ddPCR results. Results: Firefly assay demonstrated superior sensitivity and specificity with median detection of 100% at allele frequency of 0.1% for 20ng of cfDNA and zero false positive in all blank control samples. In cfDNA from plasma collected before treatment, EGFR mutation detection by Firefly assay was 94% concordant with tumor tissue ARMS. Firefly assay demonstrated strong per-variant detection-rate concordance (98%) and allele frequency concordance (R2 = 0.95) when compared with cfDNA ddPCR result. Conclusions: The amplicon based Firefly assay offers multiplex capacity, de novo variant detection, high sensitivity and specificity. Thus, Firefly assay is a kitable NGS solution for cfDNA analysis, which can help guide targeted therapy selection, drug resistance detection, and disease monitoring in NSCLC and other cancer patients. Citation Format: Lin Wang, Li Weng, Xiao Chen, Min Li, Qiaomei Guo, Wenjun Yu, Tobias Wittkop, Hongyan Wang, Malek Fahem, Shengrong Lin, Grace Q. Zhao, Jiatao Lou. Detection of actionable mutations in plasma cfDNA samples from patients with non-small cell lung carcinoma using a novel amplicon-based Firefly NGS assay [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 938.
Abstract 4270: Success of T-cell immunotherapy predicted by a mathematical model of the adaptive immune system and evolving cancer cells
Authors: Jason Thomas George, Herbert Levine
Journal: Cancer Research (2018)

Abstract It is now well-established that a patient's adaptive immune system plays an important role in identifying and eliminating cancer cells in much the same way that intracellular pathogens are cleared during infection. From a therapeutic standpoint, the adaptive immune system is unique in that it can co-evolve alongside a developing tumor. At present, the dynamics and survival probability of a mutating threat in the presence of an adaptive immune system has yet to be quantified. Here, we consider a foundational population model of a foreign invader faced with innate or adaptive immune pressure. We find that optimal growth strategies depend on whether or not the invading threat may mutate as well as the mode of immune detection. Our early model predicts that decreases in thymic output seen in advanced age may substantially affect the ability to recognize a growing population of cancer cells and recapitulates general features found in age-dependent AML incidence. This mathematical framework is able to predict the success of recent immunotherapeutic strategies, including personalized neoantigen vaccines. Our model serves as an attempt at modeling stochastic cancer evolution alongside an adaptive immune compartment. Citation Format: Jason Thomas George, Herbert Levine. Success of T-cell immunotherapy predicted by a mathematical model of the adaptive immune system and evolving 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 4270.
A Serum Protein System Affecting Contractility of the Frog Heart Present in Increased Amounts in Patients with Essential Hypertension
Authors: Stephenhajdu, Edwardleonard
Journal: Circulation Research (1958)

Plasma samples from a group of patients with severe essential hypertension were formerly shown to have a cardiotonic action on the isolated frog heart. This effect is significantly greater than that observed with plasma from normal persons or those with other diseases. The material in plasma responsible for this action is a system of 3 proteins. These proteins have been distinguished by fractionation with sodium sulfate, and are found among the serum globulins. The protein, the concentration of which determines the activity of the whole system, is called component L. When applied to the frog heart it becomes strongly bound. Two other proteins are needed, one precipitated between 0 and 17 per cent sodium sulfate, the other between 22 and 30 per cent sodium sulfate. The 0 to 17 fraction is thought to require calcium for its activity, which is bound to the protein. Calcium can be released by the addition of component L in a reaction which is dependent on temperature, reversal being possible in high calcium c...