tbuckley/cabot-search huggingface dataset:
Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains
Authors: James G. Wagner, Christina E. Barkauskas, Aaron Vose, Ryan P. Lewandowski, Jack R. Harkema, Robert M. Tighe
Journal: Environmental Health Perspectives (2020)

Epidemiological studies support the hypothesis that diabetes alters pulmonary responses to air pollutants like ozone (
Editing the LRF Repressor Binding Site in the γ-Globin Promoters Induces Therapeutically Relevant Fetal Hemoglobin Levels for the Treatment of β-Hemoglobinopathies
Authors: Giacomo Frati, Panagiotis Antoniou, Giulia Hardouin, Bochra Mlaya, Leslie Weber, Tristan Felix, Antonio Casini, Marion Rosello, Anne Chalumeau, Mario Amendola, Adrian J. Thrasher, Giandomenico Turchiano, Filippo Del Bene, Wassim El Nemer, Anna Cereseto, Jean-Paul Concordet, Carine Giovannangeli, Marina Cavazzana, Annarita Miccio
Journal: Blood (2020)
Use of Routine Echocardiographic Screening for Structural Heart Disease in At-Risk Pregnant Women in India
Authors: Amisha Patel, Lauren S. Ranard, Nicole Aranoff, Hussein Rahim, Roja Vanukuru, Sudhisha Tangalapally, Matthew Lawlor, Nadira Hamid, Susheel Kodali, Srinivas Kumar, Martin B. Leon
Journal: JACC. Cardiovascular imaging (2020)
Human rhinovirus HRV16 impairs barrier functions and regeneration of human lung vascular endothelium
Authors: Mateusz Gawrysiak, Adrian Gajewski, Robert Szewczyk, Aleksandra Likońska, Sylwia Michlewska, Magdalena Chmiela, Marek L. Kowalski, Maciej Chałubiński
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
An enolase inhibitor for the targeted treatment of ENO1-deleted cancers
Authors: Yu-Hsi Lin, Nikunj Satani, Naima Hammoudi, Victoria C. Yan, Yasaman Barekatain, Sunada Khadka, Jeffrey J. Ackroyd, Dimitra K. Georgiou, Cong-Dat Pham, Kenisha Arthur, David Maxwell, Zhenghong Peng, Paul G. Leonard, Barbara Czako, Federica Pisaneschi, Pijus Mandal, Yuting Sun, Rafal Zielinski, Susana Castro Pando, Xiaobo Wang, Theresa Tran, Quanyu Xu, Qi Wu, Yongying Jiang, Zhijun Kang, John M. Asara, Waldemar Priebe, William Bornmann, Joseph R. Marszalek, Ronald A. DePinho, Florian L. Muller
Journal: Nature Metabolism (2020)
Hemodynamic Evaluation of Heart Valve Prostheses: Paradigm Shift for Transcatheter Valves?**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: Thomas Walther, Volkmar Falk
Journal: Journal of the American College of Cardiology (2009)
15914 Effect of metabolic syndrome on efficacy and safety in patients with psoriasis treated with etanercept or tildrakizumab: Post hoc analysis of 2 phase 3 clinical studies (reSURFACE 1 and reSURFACE 2)
Authors: Alice B. Gottlieb, Nehal N. Mehta, Mark Lebwohl, Alan M. Mendelsohn, Jeff Parno, Stephen J. Rozzo, Alan Menter
Journal: Journal of the American Academy of Dermatology (2020)
Prostate Radiotherapy With Adjuvant Androgen Deprivation Therapy (ADT) Improves Metastasis-Free Survival Compared to Neoadjuvant ADT: An Individual Patient Meta-Analysis
Authors: Daniel E. Spratt, Shawn Malone, Soumyajit Roy, Scott Grimes, Libni Eapen, Scott C. Morgan, Julia Malone, Julia Craig, Robert T. Dess, William C. Jackson, Holly E. Hartman, Amar U. Kishan, Rohit Mehra, Samuel Kaffenberger, Todd M. Morgan, Zachery R. Reichert, Joshi J. Alumkal, Jeff Michalski, W. Robert Lee, Thomas M. Pisansky, Felix Y. Feng, William Shipley, Howard M. Sandler, Mathew J. Schipper, Mack Roach, Yilun Sun, Colleen A. F. Lawton
Journal: Journal of Clinical Oncology (2020)

There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa.MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS).The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups.The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.
Abstract 15112: NADPH Oxidase 4 Protects Against Development of Endothelial Dysfunction and Atherosclerosis in LDL Receptor Deficient Mice
Authors: Heike Langbein, Coy Brunssen, Anja Hofmann, Peter Cimalla, Stefan R Bornstein, Edmund Koch, Henning Morawietz
Journal: Circulation (2015)

Introduction: Endothelial dysfunction is an early step in the development of atherosclerosis. Increased formation of superoxide anions by NADPH oxidase Nox1, 2 and 5 reduce NO availability and can promote endothelial dysfunction. In contrast, recent evidence supports a vasoprotective role of H2O2 produced by main endothelial isoform Nox4. Therefore, we assessed the hypothesis genetic deletion of Nox4 influences endothelial dysfunction and atherosclerosis in the low-density lipoprotein receptor (Ldlr) knockout model. Methods and Results: Ex vivo analysis of endothelial function by Mulvany myograph showed impaired endothelial function in thoracic aorta of Nox4-/-/Ldlr-/- mice. Further progression of endothelial dysfunction by high-fat diet increased atherosclerotic plaque burden and galectin-3 staining in Nox4-/-/Ldlr-/- mice compared to Ldlr-/- mice. In addition, we obtained evidence that under physiological conditions the loss of Nox4-derived H2O2 production could partially be compensated by nNOS upregulation. Using a self-developed optical coherence tomography device we were able to analyse endothelial function by flow-mediated vasodilation in the murine saphenous artery in vivo. This new approach observed an altered flow-mediated dilation in Nox4-/- mice, indicating a role for Nox4 under physiological conditions in vivo likewise. Conclusion: Nox4 plays an important role under physiological and pathological conditions to maintain endothelial function. Loss of Nox4-derived H2O2 could partially be compensated by nNOS upregulation, but severe endothelial dysfunction is not reversible. This leads to increased atherosclerosis under atherosclerotic prone conditions.
Abstract IA03: Optimizing immunostimulatory antibodies for cancer immunotherapy
Authors: Xiaojie Yu, Anne White, Martin Glennie, Ivo Tews, Hayden Fisher, Chris Orr, Ruth French, Stephen Beers, Aymen Al'Shamkhani, Osman Dadas, Ali Roghanian, Jane Willoughby, Mark S. Cragg
Journal: Blood Cancer Discovery (2020)

Abstract Agonistic antibodies directed to immunostimulatory receptors are a currently untapped source for immunotherapy. Whereas checkpoint blockers have translated into the clinic, the rules for agonistic antibodies have been more difficult to discern and these reagents await further optimization. Here we discuss the salient properties of monoclonal antibodies (mAb) required to strongly agonize these receptors and discuss potential strategies for the future. We show that immunostimulatory mAb (ISA) can agonize key stimulatory receptors on the cell surface—many of which are from the TNFR family—and highlight the importance of isotype. Using CD40 mAb as a paradigm, we show that receptor clustering is key for ISA responses—probably mimicking ligand. This clustering can be achieved via Fc gamma receptor (FcgR) engagement or independently with the hIgG2(B) isotype. For CD40 this is highly epitope dependent, showing that epitope, isotype, and domain location all interact to drive mAb agonism. Finally, we show that isotype engineering can overcome “weak” epitopes. This can be completely independent of FcgR interaction in the case of hIgG2B, which may be of use in humans where the FcgR profile within the tumor microenvironment may vary. Citation Format: Xiaojie Yu, Anne White, Martin Glennie, Ivo Tews, Hayden Fisher, Chris Orr, Ruth French, Stephen Beers, Aymen Al'Shamkhani, Osman Dadas, Ali Roghanian, Jane Willoughby, Mark S. Cragg. Optimizing immunostimulatory antibodies for cancer immunotherapy [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr IA03.
LBA2 Sintilimab plus bevacizumab biosimilar vs sorafenib as first-line treatment for advanced hepatocellular carcinoma (ORIENT-32)2
Authors: Z. Ren, J. Fan, J. Xu, Y. Bai, A. Xu, S. Cang, C. Du, B. Liu, Q. Li, Y. Lu, Y. Chen, G. Shao, Y. Guo, Z. Chen, Y. Yang, M. Chen, Y. Wang, H. Zhou
Journal: Annals of Oncology (2020)
Colonoscopy with suboptimal bowel preparation after a positive fecal immunochemical test: what lies beneath?
Authors: Brian C. Jacobson
Journal: Endoscopy (2020)

The last two decades have seen a burgeoning of programs to systematically screen for colorectal cancer [1]. Along with colonoscopy, the use of the fecal immunochemical test (FIT) has emerged as a primary means for achieving large-scale, population-based screening [2] and is endorsed by many professional societies [2] [3]. Individuals who screen positive with a FIT are referred for colonoscopy for the removal of adenomas or to confirm and locate colon cancer. Because the positive predictive value of a FIT ranges from 34 % to 54 % [3], many of the colonoscopies performed for a positive FIT will fail to discover neoplasia. Nonetheless, a high quality colonoscopy, with adequate bowel preparation, should be performed for any individual with a positive FIT. In the setting of suboptimal bowel preparation, meaning preparation that some endoscopists might consider borderline and not inadequate, what is the likelihood that one is missing an adenoma or malignancy? And should we still make a distinction between suboptimal and inadequate bowel preparation?
Addressing Microaggressions in the Health Care Workforce—A Path Toward Achieving Equity and Inclusion
Authors: Rhonda G. Acholonu, Suzette O. Oyeku
Journal: JAMA Network Open (2020)

Dominique A. Alexis, BS; Matthew D. Kearney, MPH; J. Corey Williams, MA, MD; Chang Xu, MS; Eve J. Higginbotham, SM, MD; Jaya Aysola, MD, DTMH, MPH
Ag3PO4 decorated black urchin-like defective TiO2 for rapid and long-term bacteria-killing under visible light
Authors: Yingde Xu, Xiangmei Liu, Yufeng Zheng, Changyi Li, Kelvin Wai Kwok Yeung, Zhenduo Cui, Yanqin Liang, Zhaoyang Li, Shengli Zhu, Shuilin Wu
Journal: Bioactive Materials (2020)

Both phototherapy via photocatalysts and physical puncture by artificial nanostructures are promising substitutes for antibiotics when treating drug-resistant bacterial infectious diseases. However, the photodynamic therapeutic efficacy of photocatalysts is seriously restricted by the rapid recombination of photogenerated electron-hole pairs. Meanwhile, the nanostructures of physical puncture are limited to two-dimensional (2D) platforms, and they cannot be fully used yet. Thus, this research developed a synergistic system of Ag3PO4 nanoparticles (NPs), decorated with black urchin-like defective TiO2 (BU-TiO2-X/Ag3PO4). These NPs had a decreased bandgap compared to BU-TiO2-X, and BU-TiO2-X/Ag3PO4 (3:1) exhibited the lowest bandgap and the highest separation efficiency for photogenerated electron-hole pairs. After combination with BU-TiO2-X, the photostability of Ag3PO4 improved because the oxygen vacancy of BU-TiO2-X retards the reduction of Ag+ in Ag3PO4 into Ag0, thus reducing its toxicity. In addition, the nanospikes on the surface of BU-TiO2-X can, from all directions, physically puncture bacterial cells, thus assisting the hybrid's photodynamic therapeutic effects, alongside the small amount of Ag+ released from Ag3PO4. This achieves synergy, endowing the hybrid with high antibacterial efficacy of 99.76 ± 0.15% and 99.85 ± 0.09% against Escherichia coli and Staphylococcus aureus, respectively, after light irradiation for 20 min followed by darkness for 12 h. It is anticipated that these findings may bring new insight for developing synergistic treatment strategies against bacterial infectious diseases or pathogenic bacterial polluted environments.
Clinical characteristics and risk factors associated with severe COVID-19: prospective analysis of 1,045 hospitalised cases in North-Eastern France, March 2020
Authors: Charlotte Kaeuffer, Coralie Le Hyaric, Thibaut Fabacher, Joy Mootien, Benjamin Dervieux, Yvon Ruch, Antonin Hugerot, Yves-Jean Zhu, Valentin Pointurier, Raphael Clere-Jehl, Valentin Greigert, Loic Kassegne, Nicolas Lefebvre, Floriane Gallais, Nicolas Meyer, Yves Hansmann, Olivier Hinschberger, François Danion
Journal: Eurosurveillance (2020)

Background In March 2020, the COVID-19 outbreak was declared a pandemic by the World Health Organization. Aim Our objective was to identify risk factors predictive of severe disease and death in France. Methods In this prospective cohort study, we included patients ≥ 18 years old with confirmed COVID-19, hospitalised in Strasbourg and Mulhouse hospitals (France), in March 2020. We respectively compared patients who developed severe disease (admission to an intensive care unit (ICU) or death) and patients who died, to those who did not, by day 7 after hospitalisation. Results Among 1,045 patients, 424 (41%) had severe disease, including 335 (32%) who were admitted to ICU, and 115 (11%) who died. Mean age was 66 years (range: 20–100), and 612 (59%) were men. Almost 75% of patients with body mass index (BMI) data (n = 897) had a BMI ≥ 25 kg/m 2 (n = 661). Independent risk factors associated with severe disease were advanced age (odds ratio (OR): 1.1 per 10-year increase; 95% CrI (credible interval): 1.0–1.2), male sex (OR: 2.1; 95% CrI: 1.5–2.8), BMI of 25–29.9 kg/m 2 (OR: 1.8; 95% CrI: 1.2–2.7) or ≥ 30 (OR: 2.2; 95% CrI: 1.5–3.3), dyspnoea (OR: 2.5; 95% CrI: 1.8–3.4) and inflammatory parameters (elevated C-reactive protein and neutrophil count, low lymphocyte count). Risk factors associated with death were advanced age (OR: 2.7 per 10-year increase; 95% CrI: 2.1–3.4), male sex (OR: 1.7; 95% CrI: 1.1–2.7), immunosuppression (OR: 3.8; 95% CrI: 1.6–7.7), diabetes (OR: 1.7; 95% CrI: 1.0–2.7), chronic kidney disease (OR: 2.3; 95% CrI: 1.3–3.9), dyspnoea (OR: 2.1; 95% CrI: 1.2–3.4) and inflammatory parameters. Conclusions Overweightedness, obesity, advanced age, male sex, comorbidities, dyspnoea and inflammation are risk factors for severe COVID-19 or death in hospitalised patients. Identifying these features among patients in routine clinical practice might improve COVID-19 management.
Clinical Implications of Removing Race From Estimates of Kidney Function
Authors: James A. Diao, Gloria J. Wu, Herman A. Taylor, John K. Tucker, Neil R. Powe, Isaac S. Kohane, Arjun K. Manrai
Journal: JAMA (2020)

COVID-19 is escalating more rapidly inside detention centers compared with the US population.COVID-19 spread within facilities may be partially due to challenges faced implementing the Pandemic Response Requirements. 5An independent assessment of facilities' mitigation strategies is necessary to identify and address existing gaps in these efforts.Strategies that have proven effective in other congregate facilities, such as mass asymptomatic testing and changes in dormitory-style housing, should be considered. 6 Limitations of the study include relying on ICE's publicly available data, which may be subject to reporting delays and missing components.Given limited asymptomatic detainee testing, monthly case rates may be underestimates. 6 Comparison of rates between detainees and the US population is limited by differences in testing and reporting methods.ICE also provides limited data for facility staff; thus, this analysis represents an incomplete picture of COVID-19 epidemiology inside facilities.
James Charteris Lea Rawes
Authors: Gervase Vernon
Journal: BMJ (2020)

James Charteris Lea Rawes was the middle son of three children. He, his older sister, Annand younger brother, David, remained close all their lives. The family lived at Berkhamsted School, Hertfordshire, where James’s father was teacher and housemaster.

James went up to Jesus College, Cambridge, to study …
15410 Efficacy and tolerability of a new formulation containing Silybum marianum fruit extract in young adults with acne-prone skin: A comparative controlled study
Authors: Therese Nocera, Gwendal Josse, Lucile Garidou, Nathalie Castex Rizz, Sandrine Bessou-Touya, Jean H. Saurat
Journal: Journal of the American Academy of Dermatology (2020)
Abstract 398: Apolipoprotein CIII (apoCIII) Inhibits Insulin-dependent Endothelial Nitric Oxide Synthase (eNOS) Function In Endothelial Cells Through Protein Kinase C (PKC) βII
Authors: Akio Kawakami, Mariko Tani, Mizuko Osaka, Frank M Sacks, Kentaro Shimokado, Masayuki Yoshida
Journal: Circulation (2007)

Objective Apolipoprotein (apo) CIII, a prominent component of atherogenic dyslipidemia, is elevated in patients with type2 diabetes and insulin resistance, and independently predicts cardiovascular disease (CVD). Endothelial dysfunction is an important component of the pathophysiology of atherosclerosis, and is associated with insulin resistance. We previously reported that apoCIII has a direct effect on vascular endothelium, activating endothelial cells to recruit monocytes through PKCβ and NF-κB-dependent mechanisms. In the present study, we investigated the effect of apoCIII on insulin-dependent endothelial nitric oxide synthase (eNOS) function in endothelial cells and in the aortas of C57BL/6J mice. Methods and Results ApoCIII treatment (100μg/ml, 30 minutes) inhibited insulin-induced ISR-1/phosphatidylinositol 3-kinase (PI3K)/Akt activation in human umbilical vein endothelial cells (HUVECs). Furthermore, apoCIII reduced insulin-stimulated eNOS activation and NO release into the media. ApoCIII induced PKCβII activation in HUVECs, resulting in IRS-1 phosphorylation at pSer 616 and ERK activation. Impaired insulin-stimulated eNOS activation and NO production were restored by PKCβ inhibitor and MEK1 inhibitor to a lesser extent. In addition, treatment of C57BL/6J mice with apoCIII resulted in impaired insulin-dependent activation of PI3K/Akt/eNOS pathway in the aorta. Pretreatment with PKCβ inhibitor attenuated inhibitory effects of apoCIII. ApoCIII resides on VLDL fraction in the plasma, especially in the postprandial state. Injection of apoCIII-rich VLDL, but not apoCIII-deficient VLDL, also impaired these processes. Conclusion Our data suggest that apoCIII impairs insulin stimulation of NO production by vascular endothelium. This adverse effect of apoCIII is mediated by its activation of PKCβII which inhibits the IRS-1/PI3K/Akt/eNOS pathway. These results indicate that apoCIII not only modulates lipoprotein metabolism, but also may directly contribute to the development of diabetic complications through endothelial dysfunction. Finally, our results may point to a novel mechanism that links dyslipidemia, insulin resistance and endothelial dysfunction.
16811 Leishmaniasis in patients undergoing biologic and immunosuppressive treatment: Case-control multicenter study
Authors: Antonio Sahuquillo-Torralba, Blanca de Unamuno, A.mol/L. Quintero-Duarte, A. Mateu Puchades, Alvaro Martinez-Domenech, Aina Vila, Sergio Santos-Alarcón, Vicenç Rocamora
Journal: Journal of the American Academy of Dermatology (2020)
12883 Efficacy and safety of tildrakizumab 100 mg for plaque psoriasis in patients randomized to treatment continuation versus treatment withdrawal with retreatment upon relapse in reSURFACE 1
Authors: Wendy Cantrell, Patricia Lee, Alan M. Mendelsohn, Jeff Parno, Stephen J. Rozzo, Wilson Liao
Journal: Journal of the American Academy of Dermatology (2020)
RNA sequencing: new technologies and applications in cancer research
Authors: Mingye Hong, Shuang Tao, Ling Zhang, Li-Ting Diao, Xuanmei Huang, Shaohui Huang, Shu-Juan Xie, Zhen-Dong Xiao, Hua Zhang
Journal: Journal of Hematology & Oncology (2020)

Abstract Over the past few decades, RNA sequencing has significantly progressed, becoming a paramount approach for transcriptome profiling. The revolution from bulk RNA sequencing to single-molecular, single-cell and spatial transcriptome approaches has enabled increasingly accurate, individual cell resolution incorporated with spatial information. Cancer, a major malignant and heterogeneous lethal disease, remains an enormous challenge in medical research and clinical treatment. As a vital tool, RNA sequencing has been utilized in many aspects of cancer research and therapy, including biomarker discovery and characterization of cancer heterogeneity and evolution, drug resistance, cancer immune microenvironment and immunotherapy, cancer neoantigens and so on. In this review, the latest studies on RNA sequencing technology and their applications in cancer are summarized, and future challenges and opportunities for RNA sequencing technology in cancer applications are discussed.
Reply to Fredrik Liedberg, Pontus Eriksson, and Gottfrid Sjödahl’s Letter to the Editor re: A. Gordon Robertson, Clarice S. Groeneveld, Brian Jordan, et al. Identification of Differential Tumor Subtypes of T1 Bladder Cancer. Eur Urol;2020:533–7
Authors: Joshua J. Meeks, Lars Dyrsjkøt, A. Gordon Robertson
Journal: European Urology (2020)