tbuckley/cabot-search huggingface dataset:
Abstract PO-049: SARS-CoV-2 multiepitope vaccine constructs designed to drive long-term immunity in the majority of the population
Authors: Mark Yarmarkovich, John M. Warrington, Alvin Farrel, John M. Maris
Journal: Clinical Cancer Research (2020)

Abstract The current SARS-CoV-2 pandemic has precipitated an urgent need for a safe and effective vaccine to be developed and deployed in a highly accelerated timeframe as compared to standard vaccine development processes. Upfront selection of epitopes most likely to induce a safe and effective immune response can accelerate these efforts. Optimally designed vaccines maximize immunogenicity towards regions of proteins that contribute most to protective immunity, while minimizing the antigenic load contributed by unnecessary protein domains that may result in autoimmunity, reactogenicity, or enhanced infectivity. Adopting tools developed for population-scale characterization of HLA presentation of tumor antigens and cross-reactivity of TCRs with tumor self-antigens, we have generated an immunogenicity map of SARS-CoV-2 to inform vaccine design based on analyses across five parameters: 1) stimulation of CD4 and CD8 T cells; 2) immunogenicity across the majority of human HLA alleles; 3) targeting both evolutionarily conserved regions, as well as newly divergent regions of the virus that increase infectivity; 4) targeting linear and conformational B-cell epitopes; and 5) targeting viral regions with the highest degree of dissimilarity to the self-immunopeptidome such as to maximize safety and immunogenicity. Using these analyses, we have generated 11 SARS-CoV-2 vaccine constructs optimized for long-term immunity across the majority of the population. These constructs contain combinations of epitopes selected from our analysis such as to drive affinity-enhanced memory response in combination with current spike protein vaccine strategies, for use as T-cell vaccines, and a stand-alone vaccine designed to drive memory B- and T-cell responses in the majority of the population. Epitopes were optimized using our immunogenicity algorithm to minimize immunogenicity across the junctions between epitopes and cloned into pVAX vectors, using signal peptides targeting the lysosome, ER, and cytoplasmic secretion, such as to promote presentation to CD4, CD8, and B cells, respectively. Finally, we describe methods for identifying immunodominant epitopes arising from vaccination using barcoded, multiplexed tetramers. Vaccine constructs are currently undergoing testing in transgenic mice expressing human HLA-A2. We expect that these constructs will help drive long-term immunity across the population, targeting conserved regions across multiple coronaviruses. Citation Format: Mark Yarmarkovich, John M. Warrington, Alvin Farrel, John M. Maris. SARS-CoV-2 multiepitope vaccine constructs designed to drive long-term immunity in the majority of the population [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-049.
Epigenetic Trajectories of the Premalignant-to-Malignant Transition of Chronic Lymphocytic Leukemia
Authors: Davide Rossi
Journal: Blood Cancer Discovery (2020)

Kretzmer and colleagues show that the transition to altered methylome occurs very early in chronic lymphocytic leukemia, and once acquired, it is a clonal and extremely stable change. However, the precise time point when the leukemic clone starts deviating significantly from the normal B-cell differentiation trajectory is still elusive.See related article by Kretzmer et al., p. 54.
Radiation Exposure of Dual-Source Cardiovascular Computed Tomography in Patients With Congenital Heart Disease
Authors: Mariana De Oliveira Nunes, Dawn R. Witt, Susan A. Casey, Cynthia K. Rigsby, Anthony M. Hlavacek, Shahryar M. Chowdhury, Edward D. Nicol, Thomas Semple, John R. Lesser, B. Kelly Han
Journal: JACC. Cardiovascular imaging (2020)
Biodegradable Zn–Sr alloy for bone regeneration in rat femoral condyle defect model: In vitro and in vivo studies
Authors: Bo Jia, Hongtao Yang, Zechuan Zhang, Xinhua Qu, Xiufeng Jia, Qiang Wu, Yu Han, Yufeng Zheng, Kerong Dai
Journal: Bioactive Materials (2020)

Bone defects are commonly caused by severe trauma, malignant tumors, or congenital diseases and remain among the toughest clinical problems faced by orthopedic surgeons, especially when of critical size. Biodegradable zinc-based metals have recently gained popularity for their desirable biocompatibility, suitable degradation rate, and favorable osteogenesis-promoting properties. The biphasic activity of Sr promotes osteogenesis and inhibits osteoclastogenesis, which imparts Zn-Sr alloys with the ideal theoretical osteogenic properties. Herein, a biodegradable Zn-Sr binary alloy system was fabricated. The cytocompatibility and osteogenesis of the Zn-Sr alloys were significantly better than those of pure Zn in MC3T3-E1 cells. RNA-sequencing illustrated that the Zn-0.8Sr alloy promoted osteogenesis by activating the wnt/β-catenin, PI3K/Akt, and MAPK/Erk signaling pathways. Furthermore, rat femoral condyle defects were repaired using Zn-0.8Sr alloy scaffolds, with pure Ti as a control. The scaffold-bone integration and bone ingrowth confirmed the favorable in vivo repair properties of the Zn-Sr alloy, which was verified to offer satisfactory biosafety based on the hematoxylin-eosin (H&E) staining and ion concentration testing of important organs. The Zn-0.8Sr alloy was identified as an ideal bone repair material candidate, especially for application in critical-sized defects on load-bearing sites due to its favorable biocompatibility and osteogenic properties in vitro and in vivo.
Effects of human papillomavirus infection on prevalence of colorectal cancer: a systematic review and meta-analysis of global data
Authors: Lin Zhang, Xiaofei Li, Yang Zhao, Chunlei Hu, Adejare Atanda, Frank Wang, Hongyan Ma, Xuzhen Qin, Zhihong Qi, Xiangyi Kong, Yu Jiang
Journal: The Lancet (2020)
Abstract 2650: A New, Simple Algorithm for Diagnosing Wide QRS Complex Tachycardia: Comparison With Brugada, Vereckei and aVR Algorithms
Authors: Kenichi Sasaki
Journal: Circulation (2009)

For the differential diagnosis of wide QRS complex tachycardia (WCT), Brugada (Circulation 1991), Vereckei (Eur Heart J 2007) and Vereckei’s aVR (Heart Rhythm 2008) algorithms have been proposed. I...
306P Detection of anaplastic lymphoma kinase (ALK) mutations using circulating tumour DNA (ctDNA) in advanced non-squamous non-small cell lung cancer (non-Sq-NSCLC) in Asia
Authors: K.W.C. Lee, S.T. Wu, P.Y. Lo, C.T. Choy, T.C. Kwong, Y.T.N. Lau, L. Lin, S.W. Lau
Journal: Annals of Oncology (2020)
Obesity and the risk of primary liver cancer: A systematic review and meta-analysis
Authors: Won Sohn, Hyun Woong Lee, Sangheun Lee, Jin Hong Lim, Min Woo Lee, Chan Hyuk Park, Seung Kew Yoon
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer.Methods: This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords “obesity,” “overweight,” “body mass index (BMI),” “body weight,” “liver,” “cancer,” “hepatocellular carcinoma,” “liver cancer,” “risk,” and “mortality.” Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included.Results: A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancerrelated mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50–1.90, I&lt;sup&gt;2&lt;/sup&gt;=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02–1.81), 1.77 (95% CI, 1.56–2.01), and 3.08 (95% CI, 1.21–7.86) for BMI &gt;25 kg/m&lt;sup&gt;2&lt;/sup&gt;, &gt;30 kg/m&lt;sup&gt;2&lt;/sup&gt;, and &gt;35 kg/m&lt;sup&gt;2&lt;/sup&gt;, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14–2.27, I&lt;sup&gt;2&lt;/sup&gt;=80%).Conclusions: High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.
Maternal Docosahexaenoic Acid Supplementation and Bronchopulmonary Dysplasia in Infants
Authors: Chris H. P. van den Akker, Wes Onland, Anton H. van Kaam
Journal: JAMA (2020)

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Abstract 17312: Chemokine Receptor Down-regulation is Associated With Worse 1 Year Survival in Left Ventricular Assist Device (LVAD) Patients
Authors: Aditi Nayak, Colin Neill, Jennifer O Larsen, Indrani Halder, Timothy N Bachman, Charles McTiernan, Robert Kormos, Oriana Hunter, Ana Inashvili, Luigi Lagazzi, Jeffrey Teuteberg, Karen Hanley-Yanez, Dennis M McNamara, Marc A Simon
Journal: Circulation (2016)

Introduction: LVADs are approved for use both as Bridge To Transplant (BTT) and Destination Therapy in advanced heart failure. Current INTERMACS data reports 1 year survival with continuous flow de...
Impact of Covid-19 Related Disruptions to Colorectal Cancer Screening Programs in Three Countries: A Comparative Modelling Study
Authors: L de Jonge, J Worthington, F van Wifferen, N Iragorri, EFP Peterse, JB Lew, MJE Greuter, HA Smith, E Feletto, JHE Yong, K Canfell, VMH Coupé, I Lansdorp-Vogelaar
Journal: Endoscopy (2021)

Aims Colorectal cancer (CRC) screening programs worldwide have been disrupted during the COVID-19 pandemic. This study aimed to estimate the impact of hypothetical disruptions to organized FIT-based CRC screening programs on short- and long-term CRC incidence and mortality in three countries using microsimulation modelling.
Depletion of glioma stem cells by synergistic inhibition of mTOR and c-Myc with a biological camouflaged cascade brain-targeting nanosystem
Authors: Yuying Ma, Jinnan Zhang, Yalan Rui, Janiqua Rolle, Tian Xu, Zhiyu Qian, Yueqing Gu, Siwen Li
Journal: Biomaterials (2020)
The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review
Authors: Kottil Rammohan, Patricia K. Coyle, Elke Sylvester, Andrew Galazka, Fernando Dangond, Megan Grosso, Thomas P. Leist
Journal: Drugs (2020)

Cladribine is a purine nucleoside analog initially developed in the 1970s as a treatment for various blood cancers. Due to the molecule's ability to preferentially reduce T and B lymphocytes, it has been developed into an oral formulation for the treatment of multiple sclerosis (MS). The unique proposed mechanism of action of cladribine allows for the therapy to be delivered orally over two treatment-week cycles per year, one cycle at the beginning of the first month and one cycle at the beginning of the second month of years 1 and 2, with the potential for no further cladribine treatment required in years 3 and 4. This review summarizes the clinical development program for cladribine tablets in patients with MS, including the efficacy endpoints and results from the 2-year phase III CLARITY study in patients with relapsing-remitting MS (RRMS), the 2-year CLARITY EXTENSION study, and the phase III ORACLE-MS study in patients with a first clinical demyelinating event at risk for developing MS. Efficacy results from the phase II ONWARD study, in which cladribine tablets were administered as an add-on to interferon-β therapy in patients with RRMS, are also summarized. A review of all safety data, including lymphopenia, infections, and malignancies, is provided based on data from all trials in patients with MS, including the initial parenteral formulation studies. Based on these data, cladribine tablets administered at 3.5 mg/kg over 2 years have been approved across the globe for various forms of relapsing MS. The development of cladribine tablets for the treatment of multiple sclerosis: a comprehensive review (MP4 279143 kb).
109P Efficacy and safety of biweekly or triweekly XELOX regimen for adjuvant chemotherapy of colorectal cancer
Authors: H. Zhang, D. Wang, Z. Tong, T. Xiang, X. Tu, X. Dai, X. Zhu, Q. Fu, L. Liu, Y. Zheng, P. Zhao, W. Fang, W. Chen
Journal: Annals of Oncology (2020)
Sleep Apnea and Atrial Fibrillation: The Autonomic Link⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Samuel J. Asirvatham, Suraj Kapa
Journal: Journal of the American College of Cardiology (2009)
Relationship between supernormal lung function and long-term risk of hospitalisations and mortality: a population-based cohort study
Authors: Yunus Çolak, Børge G. Nordestgaard, Jørgen Vestbo, Peter Lange, Shoaib Afzal
Journal: European Respiratory Journal (2020)

Cardiovascular and respiratory diseases are major contributors to global deaths [1]. Although low lung function is a risk factor for early death, like hypertension and hypercholesterolaemia [2], evaluation of lung function in primary care is not prioritised as highly as blood pressure or cholesterol measurements [3]. Also, public health authorities have remained silent on major health challenges other than smoking relevant for development and preservation of normal lung function from birth to old age. It is now increasingly evident that low lung function in childhood may affect general health throughout life [4–8]. It therefore seems likely that improvement of lung function on a population-scale may be associated with lower morbidity and mortality. We therefore tested the hypothesis that supernormal lung function is associated with lower morbidity and mortality. Supernormal lung function is associated with fewer cardiovascular and respiratory events and a survival benefit independent from major risk factors <https://bit.ly/371l3ut>
Altered Mitochondria Functionality Defines a Metastatic Cell State in Lung Cancer and Creates an Exploitable Vulnerability
Authors: Chen-Hua Chuang, Madeleine Dorsch, Philip Dujardin, Sukrit Silas, Kristina Ueffing, Johanna M. Hölken, Dian Yang, Monte M. Winslow, Barbara M. Grüner
Journal: Cancer Research (2020)

Lung cancer is a prevalent and lethal cancer type that leads to more deaths than the next four major cancer types combined. Metastatic cancer spread is responsible for most cancer-related deaths but the cellular changes that enable cancer cells to leave the primary tumor and establish inoperable and lethal metastases remain poorly understood. To uncover genes that are specifically required to sustain metastasis survival or growth, we performed a genome-scale pooled lentiviral-shRNA library screen in cells that represent nonmetastatic and metastatic states of lung adenocarcinoma. Mitochondrial ribosome and mitochondria-associated genes were identified as top gene sets associated with metastasis-specific lethality. Metastasis-derived cell lines
Targeting redox-altered plasticity to reactivate synaptic function: A novel therapeutic strategy for cognitive disorder
Authors: Pei Wang, Fang Wang, Lan Ni, Pengfei Wu, Jianguo Chen
Journal: Acta Pharmaceutica Sinica B (2020)

Redox-altered plasticity refers to redox-dependent reversible changes in synaptic plasticity via altering functions of key proteins, such as N-methyl-d-aspartate receptor (NMDAR). Age-related cognitive disorders includes Alzheimer's disease (AD), vascular dementia (VD), and age-associated memory impairment (AAMI). Based on the critical role of NMDAR-dependent long-term potentiation (LTP) in memory, the increase of reactive oxygen species in cognitive disorders, and the sensitivity of NMDAR to the redox status, converging lines have suggested the redox-altered NMDAR-dependent plasticity might underlie the synaptic dysfunctions associated with cognitive disorders. In this review, we summarize the involvement of redox-altered plasticity in cognitive disorders by presenting the available evidence. According to reports from our laboratory and other groups, this "redox-altered plasticity" is more similar to functional changes rather than organic injuries, and strategies targeting redox-altered plasticity using pharmacological agents might reverse synaptic dysfunctions and memory abnormalities in the early stage of cognitive disorders. Targeting redox modifications for NMDARs may serve as a novel therapeutic strategy for memory deficits.
Author Correction: A community-based transcriptomics classification and nomenclature of neocortical cell types
Authors: Rafael Yuste, Michael Hawrylycz, Nadia Aalling, Argel Aguilar-Valles, Detlev Arendt, Ruben Armañanzas, Giorgio A. Ascoli, Concha Bielza, Vahid Bokharaie, Tobias Borgtoft Bergmann, Irina Bystron, Marco Capogna, YoonJeung Chang, Ann Clemens, Christiaan P. J. de Kock, Javier DeFelipe, Sandra Esmeralda Dos Santos, Keagan Dunville, Dirk Feldmeyer, Richárd Fiáth, Gordon James Fishell, Angelica Foggetti, Xuefan Gao, Parviz Ghaderi, Natalia A. Goriounova, Onur Güntürkün, Kenta Hagihara, Vanessa Jane Hall, Moritz Helmstaedter, Suzana Herculano-Houzel, Markus M. Hilscher, Hajime Hirase, Jens Hjerling-Leffler, Rebecca Hodge, Josh Huang, Rafiq Huda, Konstantin Khodosevich, Ole Kiehn, Henner Koch, Eric S. Kuebler, Malte Kühnemund, Pedro Larrañaga, Boudewijn Lelieveldt, Emma Louise Louth, Jan H. Lui, Huibert D. Mansvelder, Oscar Marin, Julio Martinez-Trujillo, Homeira Moradi Chameh, Alok Nath Mohapatra, Hermany Munguba, Maiken Nedergaard, Pavel Němec, Netanel Ofer, Ulrich Gottfried Pfisterer, Samuel Pontes, William Redmond, Jean Rossier, Joshua R. Sanes, Richard H. Scheuermann, Esther Serrano-Saiz, Jochen F. Staiger, Peter Somogyi, Gábor Tamás, Andreas Savas Tolias, Maria Antonietta Tosches, Miguel Turrero García, Christian Wozny, Thomas V. Wuttke, Yong Liu, Juan Yuan, Hongkui Zeng, Ed Lein
Journal: Nature Neuroscience (2021)

A Correction to this paper has been published: https://doi.org/10.1038/s41593-020-00779-0.
Statin Therapy for Subclinical Atherosclerosis in Primary Prevention: Time to Prove It?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Todd C. Villines
Journal: JACC. Cardiovascular imaging (2012)
Development and validation of a web‐based calculator to predict individualized conditional risk of site‐specific recurrence in nasopharyngeal carcinoma: Analysis of 10,058 endemic cases
Authors: Chen‐Fei Wu, Jia‐Wei Lv, Li Lin, Yan‐Ping Mao, Bin Deng, Wei‐Hong Zheng, Dan‐Wan Wen, Yue Chen, Jia Kou, Fo‐Ping Chen, Xing‐Li Yang, Zi‐Qi Zheng, Zhi‐Xuan Li, Si‐Si Xu, Jun Ma, Ying Sun
Journal: Cancer Communications (2020)

Abstract Background Conditional survival (CS) provides dynamic prognostic estimates by considering the patients existing survival time. Since CS for endemic nasopharyngeal carcinoma (NPC) is lacking, we aimed to assess the CS of endemic NPC and establish a web‐based calculator to predict individualized, conditional site‐specific recurrence risk. Methods Using an NPC‐specific database with a big‐data intelligence platform, 10,058 endemic patients with non‐metastatic stage I–IVA NPC receiving intensity‐modulated radiotherapy with or without chemotherapy between April 2009 and December 2015 were investigated. Crude CS estimates of conditional overall survival (COS), conditional disease‐free survival (CDFS), conditional locoregional relapse‐free survival (CLRRFS), conditional distant metastasis‐free survival (CDMFS), and conditional NPC‐specific survival (CNPC‐SS) were calculated. Covariate‐adjusted CS estimates were generated using inverse probability weighting. A prediction model was established using competing risk models and was externally validated with an independent, non‐metastatic stage I–IVA NPC cohort undergoing intensity‐modulated radiotherapy with or without chemotherapy ( n = 601) at another institution. Results The median follow‐up of the primary cohort was 67.2 months. The 5‐year COS, CDFS, CLRRFS, CDMFS, and CNPC‐SS increased from 86.2%, 78.1%, 89.8%, 87.3%, and 87.6% at diagnosis to 87.3%, 87.7%, 94.4%, 96.0%, and 90.1%, respectively, for an existing survival time of 3 years since diagnosis. Differences in CS estimates between prognostic factor subgroups of each endpoint were noticeable at diagnosis but diminished with time, whereas an ever‐increasing disparity in CS between different age subgroups was observed over time. Notably, the prognoses of patients that were poor at diagnosis improved greatly as patients survived longer. For individualized CS predictions, we developed a web‐based model to estimate the conditional risk of local (C‐index, 0.656), regional (0.667), bone (0.742), lung (0.681), and liver (0.711) recurrence, which significantly outperformed the current staging system ( P &lt; 0.001). The performance of this web‐based model was further validated using an external validation cohort (median follow‐up, 61.3 months), with C‐indices of 0.672, 0.736, 0.754, 0.663, and 0.721, respectively. Conclusions We characterized the CS of endemic NPC in the largest cohort to date. Moreover, we established a web‐based calculator to predict the CS of site‐specific recurrence, which may help to tailor individualized, risk‐based, time‐adapted follow‐up strategies.
14161 Ixekizumab is superior to placebo for the treatment of nail, scalp, and palmoplantar psoriasis in pediatric patients with moderate to severe plaque psoriasis
Authors: Amy S. Paller, Gabriel Alejandro Magariños, Andreas Pinter, Jennifer Cather, Stuart Keller, Claudia Rodriguez Capriles, Gaia Gallo, Emily Edson-Heredia, Lingnan Li, Kim Papp
Journal: Journal of the American Academy of Dermatology (2020)