tbuckley/cabot-search huggingface dataset:
Abstract 14025: Apolipoprotein E (ApoE) Regulates Expression of the Ubiquitin-conjugating Enzyme GTAP in Aortic Smooth Muscle Cells
Authors: Mikael Akesson, Yong-Jian Geng
Journal: Circulation (2017)

Apolipoprotein E (ApoE) is a lipoprotein critical for lipid metabolism in vivo and for the control of cholesterol efflux from macrophages in vitro. ApoE also triggers intracellular signal transduct...
Abstract IA-18: Big pediatric cancer genomic data: Discovery, precision medicine, and data sharing
Authors: Jinghui Zhang
Journal: Clinical Cancer Research (2021)

Abstract High throughput next generation sequencing (NGS) has enabled tremendous advances in our understanding of the genomic landscape of pediatric cancer, leading to discoveries of new mechanisms of tumor initiation and progression, novel targets, and diagnostic and prognostic markers. By focusing on the development of innovative computational analysis tools, we have investigated the genomic variants in pediatric cancer in the following areas: 1) genomic landscapes of &amp;gt;20 subtypes of pediatric cancer; 2) a pan-cancer study of genomes and transcriptomes of pediatric cancer which unveiled that &amp;gt;50% of the driver genes are absent in adult cancer; 3) clonal evolution of relapsed pediatric leukemia driven by therapy-induced variants bearing novel mutational signature; and 4) pathogenic germline mutations in cancer predisposition genes. These insights led to implementation of clinical cancer genomic profiling by three-platform of whole genome, whole exome and transcriptome sequencing for all eligible pediatric cancer patients at St Jude. Use of these data sets improved molecular diagnosis of pediatric cancer. Since 2015, we have analyzed &amp;gt;1,200 pediatric oncology patients providing critical data that may affect patient care. The omics data generated from our research and clinical programs can be accessed on St. Jude Cloud (https://www.stjude.cloud), a cloud-based data sharing ecosystem for accessing, analyzing and visualizing genomic data generated from &amp;gt;10,000 pediatric cancer patients, long-term survivors of pediatric cancer and &amp;gt;800 pediatric sickle cell patients. Access to three interconnected Apps on St. Jude Cloud, i.e. Genomics Platform, Pediatric Cancer (PeCan) Knowledgebase and Visualization Community, provides a unique experience for simultaneously performing advanced data analysis and enhancing the knowledgebase for pediatric cancer. Citation Format: Jinghui Zhang. Big pediatric cancer genomic data: Discovery, precision medicine, and data sharing [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-18.
Dual role of endothelial <i>Myct1</i> in tumor angiogenesis and tumor immunity
Authors: Ashraf Ul Kabir, Madhav Subramanian, Dong Hun Lee, Xiaoli Wang, Karen Krchma, Jun Wu, Teri Naismith, Carmen M. Halabi, Ju Young Kim, Fadi E. Pulous, Brian G. Petrich, Suhyun Kim, Hae-Chul Park, Phyllis I. Hanson, Hua Pan, Samuel A. Wickline, Daved H. Fremont, Changwon Park, Kyunghee Choi
Journal: Science Translational Medicine (2021)

Myct1 inhibition controls tumor angiogenesis, remodels tumor immunity, and improves immunotherapy outcomes in mouse tumor models.
Effect of healthcare system on prostate cancer-specific mortality in African American and non-Hispanic white men.
Authors: Daniella Klebaner, Patrick Travis Courtney, Brent S. Rose
Journal: Journal of Clinical Oncology (2021)

23 Background: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological differences; however, recent data suggest poorer outcomes may be related to barriers to medical care from the healthcare system in which patients receive care. We sought to evaluate potential drivers of disparities by comparing outcomes between African American and White men in the Surveillance, Epidemiology and End Results (SEER) national cancer registry and a relatively equal-access healthcare system, the Veterans Health Administration (VHA). Methods: We identified African American and White patients diagnosed with prostate cancer between 2004-2015 in the SEER and VHA databases. We analyzed metastatic disease at diagnosis with multivariable logistic regression, and PCSM with cumulative incidence analysis and sequential competing-risks regression adjusting for disease and sociodemographic factors. Results: The SEER cohort included 306,609 men (57,994 [18.9%] African American and 248,615 [81.1%] White) with a median follow-up of 5.3 years (interquartile range [IQR] 2.6-8.1 years), and the VHA cohort included 90,749 men (27,412 [30.2%] African American and 63,337 [69.8%] White) with a median follow-up of 4.7 years (IQR 2.4-7.6 years). In SEER, African American men were significantly more likely to present with metastatic disease (African American 4.3% versus White 3.0%, p&lt; 0.001; multivariable odds ratio [OR] 1.25, 95% confidence interval [CI] 1.19-1.32, p&lt; 0.001), whereas in the VHA, African American men were not significantly more likely to present with metastatic disease (African-American 3.2% versus White 3.3%, p= 0.26; multivariable OR 1.07, 95% CI 0.98-1.17, p= 0.12). In SEER, the 8-year cumulative incidence of PCSM was significantly higher for African American compared with White men (6.9% versus 5.1%, p&lt; 0.001), whereas in the VHA, African American compared with White men did not have a significantly higher 8-year cumulative incidence of PCSM (5.5% versus 5.4%, p= 0.93). African American race was significantly associated with an increased risk of PCSM in SEER (univariable subdistribution hazard ratio [SHR] 1.39, 95% CI 1.33-1.45, p&lt; 0.001), but was not significantly associated with PCSM on uni- and multivariable regression in the VHA. When adjusted for disease characteristics at diagnosis in SEER, disease extent, PSA, and Gleason score contributed to 85% of the risk of PCSM for African American men (adjusted SHR 1.06, 95% CI 1.02-1.12, p= 0.008). Conclusions: Racial disparities in PCSM were present in a national cohort, SEER, but not as pronounced in a relatively equal-access healthcare system, the VHA, potentially due to differences in metastatic disease at diagnosis among African American and White men between cohorts. These findings may be attributable to reduced barriers to care in the VHA.
Cylindrical polymer brushes-anisotropic unimolecular micelle drug delivery system for enhancing the effectiveness of chemotherapy
Authors: Shuang Bai, Die Jia, Xianbin Ma, Mengyun Liang, Peng Xue, Yuejun Kang, Zhigang Xu
Journal: Bioactive Materials (2021)

Polymer systems can be designed into different structures and morphologies according to their physical and chemical performance requirements, and are considered as one of the most promising controlled delivery systems that can effectively improve the cancer therapeutic index. However, the majority of the polymer delivery systems are designed to be simple spherical nanostructures. To explore morphology/size-oriented delivery performance optimization, here, we synthesized three novel cylindrical polymer brushes (CPBs) by atom transfer radical polymerization (ATRP), which were cellulose-g-(CPT-b-OEGMA) (CCO) with different lengths (~86, ~40, and ~21 nm). The CPBs are composed of bio-degradable cellulose as the carrier, poly(ethylene glycol) methyl ether methacrylate (OEGMA) as hydrophily block, and glutathione (GSH)-responsive hydrophobic camptothecin (CPT) monomer as loaded anticancer drug. By controlling the chain length of the initiator, three kinds of polymeric prodrugs with different lengths (CCO-1, CCO-2, and CCO-3) could be self-organized into unimolecular micelles in water. We carried out comparative studies of three polymers, whose results verified that the shorter CPBs exhibited higher drug release efficiency, more cellular uptake, and enhanced tumor permeability, accompanied by shortened blood circulation time and lower tumor accumulation. As evidenced by in vivo experiments, the shorter CPBs exhibited higher anti-tumor efficiency, revealing that the size advantage has a higher priority than the anisotropic structure advantage. This provided vital information as to design an anisotropic polymer-based drug delivery system for cancer therapy.
Functional convergence of a germline-encoded neutralizing antibody response in rhesus macaques immunized with HCV envelope glycoproteins
Authors: Fang Chen, Netanel Tzarum, Xiaohe Lin, Erick Giang, Rodrigo Velázquez-Moctezuma, Elias H. Augestad, Kenna Nagy, Linling He, Mayda Hernandez, Mallorie E. Fouch, Ariadna Grinyó, Deborah Chavez, Benjamin J. Doranz, Jannick Prentoe, Robyn L. Stanfield, Robert Lanford, Jens Bukh, Ian A. Wilson, Jiang Zhu, Mansun Law
Journal: Immunity (2021)
Acute lymphoblastic leukemia: A population‐based study of outcome in the <scp>U</scp>nited <scp>S</scp>tates based on the surveillance, epidemiology, and end results (<scp>SEER</scp>) database, <scp>1980</scp>–<scp>2017</scp>
Authors: Koji Sasaki, Elias Jabbour, Nicholas J. Short, Nitin Jain, Farhad Ravandi, Ching‐Hon Pui, Hagop Kantarjian
Journal: American Journal of Hematology (2021)

The treatment in acute lymphoblastic Leukemia (ALL) has evolved and improved dramatically over the past four decades. We assessed the outcome of ALL overall, and the two major subsets of Philadelphia chromosome (Ph)-positive and Ph-negative ALL by age, time periods, ethnicity, median household income, and geographic county area. A total of 12 788 patients diagnosed with ALL from 1980 to 2017 were included. We performed an analysis to better evaluate the outcome evolution in ALL according to time period and patient's demographic factors. The overall 5-year survival rates have improved significantly over time, from 51% before 1990 to 72% since 2010. The survival rates for children (age 0 to 14 years) and adolescents (age 15 to 19 years) have improved from 73% and 55% before 1990 to 93% and 74% since 2010, respectively. Similarly, the rates had improved from 33% to 59% for adults 20 to 29 years old, 24% to 59% for 30 to 39 years old, and 14% to 43% for 40 to 59 years old between the two time periods. The rates remained under 30% in older patients (60+ years). Since 2010, patients with Ph-negative ALL had 5-year survival rate of 73% and those with Ph-positive ALL 50%. African Americans, Hispanic ethnicity, and lower household income were associated with inferior survival. The outcome of patients with ALL showed continued improvement across all age groups in the US. The recent introduction of targeted therapies, together with optimized supportive care, will continue to improve outcomes, particularly in older patients.
Blinatumomab in B-Cell Acute Lymphoblastic Leukemia with Positive Minimal Residual Disease: Initial Results of a Phase II Trial
Authors: Abhishek Maiti, Hagop M. Kantarjian, Nicholas J Short, Maria Khouri, Koichi Takahashi, Maro Ohanian, Gautam Borthakur, Marina Konopleva, Naval Daver, Zeev Estrov, Yesid Alvarado, Philip A Thompson, Nitin Jain, Farhad Ravandi, Guillermo Garcia-Manero, Carissa N Cholick, Rita Khouri, Susan M. O'Brien, Elias J. Jabbour
Journal: Blood (2017)
“Physical activity as a moderator for obstructive sleep apnoea and cardiometabolic risk in the EPISONO study.” Marcos Mônico-Neto, Hanna Karen Moreira Antunes, Ronaldo Vagner Thomatieli dos Santos, Vânia D'Almeida, Altay Alves Lino de Souza, Lia Rita Azeredo Bittencourt and Sergio Tufik. Eur Respir J 2018; 52: 1701972.
Journal: European Respiratory Journal (2018)
Severe Hypoglycemia Risk With Long-Acting Insulin Analogs vs Neutral Protamine Hagedorn Insulin
Authors: Marie C. Bradley, Yoganand Chillarige, Hana Lee, Xiyuan Wu, Shruti Parulekar, Stella Muthuri, Michael Wernecke, Thomas E. MaCurdy, Jeffrey A. Kelman, David J. Graham
Journal: JAMA Internal Medicine (2021)

<h3>Importance</h3> Previous studies have found that the risk of severe hypoglycemia does not differ between long-acting insulin analogs and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. However, these studies did not focus on patients 65 years or older, who are at an increased risk for hypoglycemia, or did not include patients with concomitant prandial insulin use. <h3>Objective</h3> To examine the risk of emergency department (ED) visits or hospitalizations for hypoglycemia among older community-residing patients with type 2 diabetes who initiated long-acting insulin or NPH insulin in real-world settings. <h3>Design, Setting, and Participants</h3> This retrospective, new-user cohort study assessed Medicare beneficiaries 65 years or older who initiated insulin glargine (n = 407 018), insulin detemir (n = 141 588), or NPH insulin (n = 26 402) from January 1, 2007, to July 31, 2019. <h3>Exposures</h3> Insulin glargine, insulin detemir, and NPH insulin. <h3>Main Outcomes and Measures</h3> The primary outcome was time to first ED visit or hospitalization for hypoglycemia, defined using a modified validated algorithm. Propensity score–weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs. The risk of recurring hypoglycemia events was estimated using the Andersen-Gill model. Post hoc analyses were conducted investigating possible effect modification by age. <h3>Results</h3> Of the 575 008 patients initiating use of insulin (mean [SD] age 74.9 [6.7] years; 53% female), 407 018 used glargine, 141 588 used detemir, and 26 402 used NPH insulin. The study included 7347 ED visits or hospitalizations for hypoglycemia (5194 for glargine, 1693 for detemir, and 460 for NPH insulin, with a median follow-up across the 3 cohorts of 0.37 years (interquartile range, 0.20-0.76 years). Initiation of glargine and detemir use was associated with a reduced risk of hypoglycemia compared with NPH insulin use (HR for glargine vs NPH insulin, 0.71; 95% CI, 0.63-0.80; HR, detemir vs NPH insulin, 0.72; 95% CI, 0.63-0.82). The HRs were similar for the recurrent event analysis. The protective association of long-acting insulin analogs varied by age and was not seen with concomitant prandial insulin use. <h3>Conclusions and Relevance</h3> In this cohort study, initiation of long-acting analogs was associated with a lower risk of ED visits or hospitalizations for hypoglycemia compared with NPH insulin in older patients with type 2 diabetes in Medicare. However, this association was not seen with concomitant prandial insulin use.
Money, market, media, and vaccine nationalism in the pandemic era
Authors: Padmanabhan Badrinath
Journal: BMJ (2021)

The BMJ reports preliminary efficacy data from the phase III trial of the Novavax vaccine.1 In this pandemic era, the rules of scientific publication and peer review have been rewritten, and important studies are reported not through peer reviewed publications but through press releases to the market. This is true for both Novavax2 and Johnson & Johnson3 vaccines, which have the potential to make money for shareholders or increase investment. Novavax proclaimed: “NVX-CoV2373 is the first vaccine to …
Why mechanical dyssynchrony remains relevant to cardiac resynchronization therapy. Letter regarding the article ‘Optimized implementation of cardiac resynchronization therapy: a call for action for referral and optimization of care: a joint position statement from the Heart Failure Association (HFA), European Heart Rhythm Association (EHRA), and European Association of Cardiovascular Imaging (EACVI) of the European Society of Cardiology’
Authors: Alexis Puvrez, Jürgen Duchenne, John Gorcsan, Thomas H. Marwick, Otto A. Smiseth, Jens‐Uwe Voigt
Journal: European Journal of Heart Failure (2021)
Polydopamine nanoparticle-dotted food gum hydrogel with excellent antibacterial activity and rapid shape adaptability for accelerated bacteria-infected wound healing
Authors: Qiankun Zeng, Yuna Qian, Yijing Huang, Feng Ding, Xiaoliang Qi, Jianliang Shen
Journal: Bioactive Materials (2021)

Most commonly used wound dressings have severe problems, such as an inability to adapt to wound shape or a lack of antibacterial capacity, affecting their ability to meet the requirements of clinical applications. Here, a nanocomposite hydrogel (XKP) is developed by introducing polydopamine nanoparticles (PDA NPs) into a food gum matrix (XK, consisting of xanthan gum and konjac glucomannan, both FDA-approved food thickening agents) for skin wound healing. In this system, the embedded PDA NPs not only interact with the food gum matrix to form a hydrogel with excellent mechanical strength, but also act as photothermal transduction agents to convert near-infrared laser radiation to heat, thereby triggering bacterial death. Moreover, the XKP hydrogel has high elasticity and tunable water content, enabling it to adapt to the shape of the wound and insulate it, providing a moist environment suitable for healing. In-vivo skin wound healing results clearly demonstrate that XKP can significantly accelerate the healing of wounds by reducing the inflammatory response and promoting vascular reconstruction. In summary, this strategy provides a simple and practical method to overcome the drawbacks of traditional wound dressings, and provides further options when choosing suitable wound healing materials for clinical applications.
Detection of Adult Pancreatoblastoma by 18F-FDG and 68Ga-DOTATATE PET/MR
Authors: Jinxin Zhou, Jing Xie, Yu Pan, Yifan Zhang
Journal: Clinical Nuclear Medicine (2021)

Abstract A 36-year-old asymptomatic woman was incidentally found to have a huge mass in the pancreas by ultrasound during routine health screening. The mass was suspected of neuroendocrine tumor or solid pseudopapillary tumor by subsequent abdominal CT. 18 F-FDG and 68 Ga-DOTATATE PET/MR were acquired for presurgical assessment of the tumor invasion and malignant potential, which revealed intense FDG uptake and mild DOTATATE uptake. The tumor was completely resected, and postsurgical pathology demonstrated pancreatoblastoma with neuroendocrine manifestations. This case showed the metabolic and biological features of pancreatoblastoma on the 18 F-FDG and 68 Ga-DOTATATE PET/MR.
mRNA in cancer immunotherapy: beyond a source of antigen
Authors: Lien Van Hoecke, Rein Verbeke, Heleen Dewitte, Ine Lentacker, Karim Vermaelen, Karine Breckpot, Sandra Van Lint
Journal: Molecular Cancer (2021)

Abstract mRNA therapeutics have become the focus of molecular medicine research. Various mRNA applications have reached major milestones at high speed in the immuno-oncology field. This can be attributed to the knowledge that mRNA is one of nature’s core building blocks carrying important information and can be considered as a powerful vector for delivery of therapeutic proteins to the patient. For a long time, the major focus in the use of in vitro transcribed mRNA was on development of cancer vaccines, using mRNA encoding tumor antigens to modify dendritic cells ex vivo. However, the versatility of mRNA and its many advantages have paved the path beyond this application. In addition, due to smart design of both the structural properties of the mRNA molecule as well as pharmaceutical formulations that improve its in vivo stability and selective targeting, the therapeutic potential of mRNA can be considered as endless. As a consequence, many novel immunotherapeutic strategies focus on the use of mRNA beyond its use as the source of tumor antigens. This review aims to summarize the state-of-the-art on these applications and to provide a rationale for their clinical application.
SAPROCAN: Saracatinib (AZD0530) and docetaxel in metastatic,castrate-refractory prostate cancer (mCRPC)—A phase I/randomized phase II study by the United Kingdom National Cancer Research Institute Prostate Group.
Authors: Robert J. Jones, Amit Bahl, Johann S. De Bono, Christy Ralph, Tony Elliott, Angus Robinson, Charlotte Westbury, Alison Jane Birtle, John Nicholas Staffurth, Andrew Protheroe, Balaji Venugopal, Fiona Thomson, Chantevy Pou, Karen Morris, Jonathan Tugwood, Laura Divers, Carol Hopkins, Elaine McCartney, Caroline Kelly, Simon J. Crabb
Journal: Journal of Clinical Oncology (2021)

107 Background: Saracatinib is an orally-available, highly selective inhibitor of Abl and Src family members. It is an ATP-competitive tyrosine kinase inhibitor. Preclinical data suggested that the combination of a Src kinase inhibitor and docetaxel is synergistic, and Src kinase activity was also implicated in the bone’s metabolic response to cancer metastases. Methods: Patients with mCRPC were initially enrolled in an open-label, dose escalation phase I trial of oral saracatinib (cohorts of 50mg, 125mg and 175mg daily) with docetaxel (75mg/m 2 ) in a 3+3 design. Subsequent patients were randomised 1:1 between saracatinib 175mg and placebo once daily. Pharmacokinetics (PK) of docetaxel were explored in phase I to exclude significant drug-drug interaction. The primary endpoint of phase II was biochemical or radiographic progression free survival (PFS). Secondary endpoints included overall survival (OS), safety and tolerability. Changes in circulating tumour cell (CTC) counts were also measured. The phase II was designed with a 1-sided alpha of 0.2 with 90% power to detect a hazard ratio (HR) for PFS of 0.67. Results: 10 patients were enrolled in phase I and 142 in the randomised phase II. No dose limiting toxicities or PK interactions were observed and the recommended dose for phase II was 175mg saracatinib daily and 75mg/m 2 docetaxel every 21 days. In phase II, the HR for PFS was 1.35 (80% confidence interval (CI) 1.07 to 1.70). The HR for OS was 1.42 (1.08 – 1.81). 41/71 and 29/71 experienced treatment related toxicities of grade 3 or above in the saracatinib and placebo arms respectively. 10/19 (53%) and 14/27 (52%) evaluable patients demonstrated a reduction in CTCs from ≥5 to &lt; 5 /7.5ml blood at 6 weeks after starting saracatinib and placebo respectively. Conclusions: Saracatinib, in combination with docetaxel, adds toxicity and not efficacy in mCRPC. This combination should not be developed further in combination with docetaxel in the treatment of mCRPC. Clinical trial information: ISRCTN22566729.