tbuckley/cabot-search huggingface dataset:
Cerebral cavernous malformations are driven by ADAMTS5 proteolysis of versican
Authors: Courtney C. Hong, Alan T. Tang, Matthew R. Detter, Jaesung P. Choi, Rui Wang, Xi Yang, Andrea A. Guerrero, Carl F. Wittig, Nicholas Hobson, Romuald Girard, Rhonda Lightle, Thomas Moore, Robert Shenkar, Sean P. Polster, Lauren M. Goddard, Aileen A. Ren, N. Adrian Leu, Stephanie Sterling, Jisheng Yang, Li Li, Mei Chen, Patricia Mericko-Ishizuka, Lukas E. Dow, Hideto Watanabe, Markus Schwaninger, Wang Min, Douglas A. Marchuk, Xiangjian Zheng, Issam A. Awad, Mark L. Kahn
Journal: The Journal of Experimental Medicine (2020)

Cerebral cavernous malformations (CCMs) form following loss of the CCM protein complex in brain endothelial cells due to increased endothelial MEKK3 signaling and KLF2/4 transcription factor expression, but the downstream events that drive lesion formation remain undefined. Recent studies have revealed that CCM lesions expand by incorporating neighboring wild-type endothelial cells, indicative of a cell nonautonomous mechanism. Here we find that endothelial loss of ADAMTS5 reduced CCM formation in the neonatal mouse model. Conversely, endothelial gain of ADAMTS5 conferred early lesion genesis in the absence of increased KLF2/4 expression and synergized with KRIT1 loss of function to create large malformations. Lowering versican expression reduced CCM burden, indicating that versican is the relevant ADAMTS5 substrate and that lesion formation requires proteolysis but not loss of this extracellular matrix protein. These findings identify endothelial secretion of ADAMTS5 and cleavage of versican as downstream mechanisms of CCM pathogenesis and provide a basis for the participation of wild-type endothelial cells in lesion formation.
P-150 Khorana and PROTECHT scores in predicting the risk of venous thromboembolism in pancreatic cancer: Which performed better?
Authors: S. Dâmaso, R. Paiva, I. Pinho, M. Martins, R. Brás, A. Costa, A. Quintela, C. Pinto, I. Vendrell, L. Costa
Journal: Annals of Oncology (2020)
Fortnightly Review: Drugs in sport
Authors: D. MacAuley
Journal: BMJ (1996)

The use of drugs to enhance performance in sport will not go away.Athletes seek every competitive advantage and the rewards of success at top level are great, both financially and in personal glory.Almost all top level competitors are full time and, even if not paid, are to all purposes professional.There is huge pressure to train longer and harder and to take a scientific approach to nutrition and fluid and electrolyte balance, to seek every biomechanical and psychological advantage.It is almost inevitable that some will seek an advantage through drugs.Though there may be little clear objective scientific evidence of a benefit to be gained from drug use, what evidence there is supports the widespread belief among athletes that drugs help.Indeed, many believe that it is impossible to succeed without drugs.Though an athlete's motivation in taking drugs is understand- able, we cannot condone it.Firstly, it can be dangerous to the athlete's health and, secondly, it is against all principles of fair competition. MethodA systematic search ofthe literature is unlikely to tell the complete story in any review of drug abuse in sport.Doping in sport is essentially an underground activity with little formal published research in a topic which should not officially exist.Much of what is common knowledge is cloaked in rumour, suspicion, and suggestion, and the strategies adopted by athletes seem to be founded more on empiricism than published scientific data.The information presented in this review has been identified from several sources.A Medline search from 1966 to 1996 identified 620 references to the term "doping in sports."With the search restricted to humans (504) and to publications in English there were 389 references.Those references were subclassified into publications identfying side effects, prevalence, meth- ods of detection, and a fourth group composed of edito- rials, opinions, and reviews.Further references were identified from a search of the National Sports Medicine Institute database and a hand search of the past five years of the British Journal of Sports Medicine.
Abstract 16633: Rates and Patterns of Inappropriate Dosing for Non-vitamin K Oral Anticoagulant Among Canadian Atrial Fibrillation Patients: Insights From a Prospective Registry
Authors: Christopher Labos, Andrew Ha, Mahesh Kajil, Michelle Tsigoulis, Jafna Cox, Paul Dorian, John Mancini, David Gladstone, Evan Lockwood, Ashfaq Shuaib, Hridyesh Sikri, Narendra Singh, Milan Gupta
Journal: Circulation (2017)

Background: Non-vitamin K oral anticoagulants (NOAC) are commonly prescribed to prevent stroke for at-risk atrial fibrillation (AF) patients. Dosing reduction of these agents is recommended by Heal...
Imaging Fibroblast Activation Protein Alpha Improves Diagnosis of Metastatic Prostate Cancer with Positron Emission Tomography
Authors: Hallie M. Hintz, Joseph P. Gallant, Donald J. Vander Griend, Ilsa M. Coleman, Peter S. Nelson, Aaron M. LeBeau
Journal: Clinical Cancer Research (2020)

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal, heterogeneous disease with few therapeutic strategies that significantly prolong survival. Innovative therapies for mCRPC are needed; however, the development of new therapies relies on accurate imaging to assess metastasis and monitor response. Standard imaging modalities for prostate cancer require improvement and there remains a need for selective and sensitive imaging probes that can be widely used in patients with mCRPC.We evaluated the transmembrane protease fibroblast activation protein alpha (FAP) as a targetable cell surface antigen for mCRPC. Genomic and IHC analyses were performed to investigate FAP expression in prostate cancer. Our FAP-targeted antibody imaging probe, [89Zr]Zr-B12 IgG, was evaluated by PET/CT imaging in preclinical prostate cancer models.Analysis of patient data documented FAP overexpression in metastatic disease across tumor subtypes. PET imaging with [89Zr]Zr-B12 IgG demonstrated high tumor uptake and long-term retention of the probe in the preclinical models examined. FAP-positive stroma tumor uptake of [89Zr]Zr-B12 IgG was 5-fold higher than the isotype control with mean %ID/cc of 34.13 ± 1.99 versus 6.12 ± 2.03 (n = 3/group; P = 0.0006) at 72 hours. Ex vivo biodistribution corroborated these results documenting rapid blood clearance by 24 hours and high tumor uptake of [89Zr]Zr-B12 IgG by 72 hours.Our study reveals FAP as a target for imaging the tumor microenvironment of prostate cancer. Validation of [89Zr]Zr-B12 IgG as a selective imaging probe for FAP-expressing tumors presents a new approach for noninvasive PET/CT imaging of mCRPC.
P-292 Locally advanced esophageal cancer: Pattern of care, treatment outcomes and prognostic factors over a 20-year experience at the Modena Cancer Centre
Authors: F. Canino, C. Santini, A. Bocconi, S. Benatti, E. Pettorelli, L. Reggiani Bonetti, S. Caramaschi, A. Spallanzani, F. Gelsomino, G. Luppi, M. Dominici, M. Salati
Journal: Annals of Oncology (2020)
Abstract 10297: Altered Cardiac Response of Nitric Oxide and cGMP After Heart Failure--Assessment by Pressure-Volume Analysis
Authors: Xiaowei Zhang, Che Ping Cheng, Peng Zhou, Zhi Zhang, Satoshi Masutani, Michael F Callahan, Dalane Kitzman, David Herrington, Heng-Jie Cheng
Journal: Circulation (2019)

Background: It is well recognized that in heart failure (HF) neurohormonal activation has important functional consequences. The biological activities of many neuropeptides are mediated by intracel...
FRI0227 Monoclonal secretion duiring sjogren’s syndrome (ss)
Authors: EY Varlamova, VI Vasiliev, EY Saridi, MV Simonova, NS Shornikova, VR Gorodetsky, NN Tupizyn, EN Sholokhova
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Finding of monoclonal immunoglobulins and light chains in serum and urine of SS pts suggests the possibility of SS transformation into malignant lympho-proliferative diseases. <h3>Objectives</h3> To characterise the spectrum of monoclonal secretion in SS, to evaluate the role of monoclonal immunoglobulinopathy in the development of I-secreting lymphomas in SS. <h3>Methods</h3> 24 females aged 25–75 years (49.2(3.4) with SS duration of 2–28 years admitted into Institute of Rheumatology during 2000 had typing of monoclonal immunoglobulins or their fragments with the help of: I – serum agarosa gel and concentrated urine electrophoresis with subsequent densitometry of electrophoregraphs, 2 – immunofixation and immunoelectrophoresis with monospesific anti-serums ã, á, ì, å, ä, ê, ë. <h3>Results</h3> IgMk-3, IgAk-2 monoclonal immunoglobulins were found in 5 pts (25%) in blood serum, Bens-Johns protein (BJk) was found in urine of 3 pts and IgMk in one patient. Thorough examination of pts with monoclonal secretion with carrying out of immunophenotyping of bioptates on lymphatic nodes and small salivary glands on lower lip enabled us to diagnose big cell lymphoma (2-ptorein BJk in the urine, IgMk in serum in 4 pts and plasmacytoma (IgGk) in one patient. It was not possible to confirm the presence of malignant lymphatic proliferation in this study in pts with IgAk (2), IgMk (1) monoclonal secretion in serum and vestige protein secretion BJk in the urine. <h3>Conclusion</h3> Revealing of monoclonal immunoglobulins and light chains of immunoglobulins enables us to suggest the appearing of malignant lymphatic proliferation in SS pts and during further immunophenotyping of lymphatic nodes to diagnose the development of immunosecreting lymphomas in the half (55%) of pts.
P-100 Quality of life assessment and reporting in gastric cancer treatment: A systematic review of phase 3 clinical trials published between 2010 and 2019
Authors: A. Ricci, M. Nigro, M. Mosca, F. Dall'Olio, A. Rizzo, C. Bonucci, N. Tober, M. Mandruzzato, R. Pagani, V. Mollica, I. Maggio, M. Massucci, L. Rojas LLimpe, F. Di Fabio, A. Ardizzoni
Journal: Annals of Oncology (2020)
P-194 The use of cytoreduction and HIPEC in the treatment of peritoneal carcinomatosis: The experience in Ramón y Cajal University Hospital
Authors: J. Esteban Villarrubia, P. Reguera Puertas, J. Galindo López, J. Cabañas Moreno, M. Cuadrado Ayuso, S. Corral Moreno, F. Longo, V. Pachón Olmos, M. Rodriguez Garrote, R. Fuentes, M. Villamayor Delgado, M. Vaz, C. Guillén-Ponce, S. Sánchez Picot, E. Canales Lachen, E. Serrano Tamayo, C. Pueyo López, M. Sánchez Cuervo, A. Perucho González, N. Martínez, R. Ferreiro Monteagudo
Journal: Annals of Oncology (2020)
The Current Status of Women in Surgery
Authors: Elizabeth H. Stephens, Christine A. Heisler, Sarah M. Temkin, Pringl Miller
Journal: JAMA Surgery (2020)

Despite women composing half of current medical school classes, surgical specialties still struggle to attract and retain women. Even after successful recruitment into training, women surgeons continue to face gender bias and various obstacles to career advancement, including lower rates of surgical residency completion, board certification, and professional advancement. Gender inequality in medicine has drawn attention; particular consideration regarding the status of women in surgery is warranted. We review research delineating disparities and investigating the causes underlying such issues, and most importantly, we propose recommended action.Recruitment of women into surgery is increasing as more women are visible in the specialty, and forthcoming measures to encourage mentorship and rectify issues related to pregnancy and burnout will likely improve this. However, obstacles to career development for women surgeons, including residency/fellowship support, mentorship/sponsorship, leadership, work-life balance, and pay equity remain. More importantly, gender discrimination continues, originating from conscious and unconscious bias, which is remedied only by recognition and deliberate correction. Several organizations have proactively recommended measures to cultivate gender equity for women surgeons, which require implementation to effect meaningful change. While the first step is recognition of the issues and underlying etiologies, further action is needed in combating such disparities and establishing a culture of equity for women in surgery.Opportunities for women in surgery have improved, although much work remains to make the surgical workplace supportive of women, empowering them to optimally contribute. These efforts will benefit organizations, the community, future generations of surgeons, and most importantly, profoundly and positively affect the care of patients.
Fucoidan-based, tumor-activated nanoplatform for overcoming hypoxia and enhancing photodynamic therapy and antitumor immunity
Authors: Chu-Hung Chung, Kun-Ying Lu, Wei-Cheng Lee, Wen-Jing Hsu, Wen-Fu Lee, Jia-Zih Dai, Pei-Wei Shueng, Cheng-Wei Lin, Fwu-Long Mi
Journal: Biomaterials (2020)
SO-26 Clinical efficacy of combined BRAF, MEK, and PD-1 inhibition in BRAFV600E colorectal cancer patients
Authors: R. Corcoran, M. Giannakis, J. Allen, J. Chen, K. Pelka, S. Chao, J. Meyerhardt, A. Enzinger, P. Enzinger, N. McCleary, M. Yugelun, T. Abrams, K. Kanter, E. Van Seventer, W. Bradford, I. Fetter, G. Siravegna, J. Tian, J. Clark, D. Ryan, N. Hacohen, A. Parikh
Journal: Annals of Oncology (2020)
Abstract 10774: Restoration of Normal Cardiomyocyte Basal and Beta-Adrenergic Receptor (AR) Subtype Modulation in Heart Failure by Chronic Beta3-AR Deficiency
Authors: Zhe Chen, Yixi Liu, Heng-Jie Cheng, Peng Zhou, XiaoWei Zhang, Tiankai Li, Zhi Zhang, Michael F Callahan, Delane Kitzman, Che Ping Cheng
Journal: Circulation (2018)

Background: We have previously shown that heart failure (HF) is associated with upregulation of β3-adrenergic receptor (AR)-mediated cardiac inhibitory pathway. Isoproterenol (ISO)-induced HF was p...
Virus shedding dynamics in asymptomatic and mildly symptomatic patients infected with SARS-CoV-2
Authors: W. Li, Y.-Y. Su, S.-S. Zhi, J. Huang, C.-L. Zhuang, W.-Z. Bai, Y. Wan, X.-R. Meng, L. Zhang, Y.-B. Zhou, Y.-Y. Luo, S.-X. Ge, Y.-K. Chen, Y. Ma
Journal: Clinical Microbiology and Infection (2020)
Suppression of ABCE1-Mediated mRNA Translation Limits N-MYC–Driven Cancer Progression
Authors: Jixuan Gao, MoonSun Jung, Chelsea Mayoh, Pooja Venkat, Katherine M. Hannan, Jamie I. Fletcher, Alvin Kamili, Andrew J. Gifford, Eric P. Kusnadi, Richard B. Pearson, Ross D. Hannan, Michelle Haber, Murray D. Norris, Klaartje Somers, Michelle J. Henderson
Journal: Cancer Research (2020)

Abstract The ability of the N-MYC transcription factor to drive cancer progression is well demonstrated in neuroblastoma, the most common extracranial pediatric solid tumor, where MYCN amplification heralds a poor prognosis, with only 11% of high-risk patients surviving past 5 years. However, decades of attempts of direct inhibition of N-MYC or its paralogues has led to the conclusion that this protein is “undruggable.” Therefore, targeting pathways upregulated by N-MYC signaling presents an alternative therapeutic approach. Here, we show that MYCN-amplified neuroblastomas are characterized by elevated rates of protein synthesis and that high expression of ABCE1, a translation factor directly upregulated by N-MYC, is itself a strong predictor of poor clinical outcome. Despite the potent ability of N-MYC in heightening protein synthesis and malignant characteristics in cancer cells, suppression of ABCE1 alone selectively negated this effect, returning the rate of translation to baseline levels and significantly reducing the growth, motility, and invasiveness of MYCN-amplified neuroblastoma cells and patient-derived xenograft tumors in vivo. The growth of nonmalignant cells or MYCN-nonamplified neuroblastoma cells remained unaffected by reduced ABCE1, supporting a therapeutic window associated with targeting ABCE1. Neuroblastoma cells with c-MYC overexpression also required ABCE1 to maintain cell proliferation and translation. Taken together, ABCE1-mediated translation constitutes a critical process in the progression of N-MYC–driven and c-MYC–driven cancers that warrants investigations into methods of its therapeutic inhibition. Significance: These findings demonstrate that N-MYC–driven cancers are reliant on elevated rates of protein synthesis driven by heightened expression of ABCE1, a vulnerability that can be exploited through suppression of ABCE1.
P-106 Liver metastasis in colorectal cancer: Management and survival outcomes of liver metastasectomy in a single-center analysis
Authors: M. Vilaca, D. Silva, D. Magalhães, E. Cipriano, A. Tavares, R. Peixoto, M. Salgado, A. Mesquita, C. Sottomayor
Journal: Annals of Oncology (2020)
P-286 Exploring chemotherapy holiday in pancreatic cancer patients responding to upfront nab-paclitaxel-gemcitabine containing regimens
Authors: M. Macchini, U. Peretti, G. Orsi, S. Zanon, M. Valente, E. Mazza, S. Cascinu, M. Reni
Journal: Annals of Oncology (2020)
The Beginning of Genomic Therapies for ALS
Authors: Orla Hardiman, Leonard H. van den Berg
Journal: New England Journal of Medicine (2020)

Amyotrophic lateral sclerosis (ALS) is a heterogeneous disorder of progressive degeneration of upper and lower motor neurons that typically leads to death from ventilatory failure within 5 years after the onset of illness. Genetic factors account for half of the variance in the risk of the disorder.1 Up to 15% of patients with ALS have a family history of ALS or frontotemporal dementia. In populations of European origin, variants in the gene encoding superoxide dismutase 1 (SOD1) account for 13 to 20% of familial ALS, with variants in C9orf72, TDP43, and FUS accounting for most of the remainder.2 Mutations in . . .
Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic
Authors: Asma Khalil, Peter von Dadelszen, Tim Draycott, Austin Ugwumadu, Pat O’Brien, Laura Magee
Journal: JAMA (2020)

This study compares pregnancy outcomes, including rates of stillbirth (fetal death ≥24 weeks' gestation), preterm and cesarean delivery, and neonatal unit admission in the months preceding vs during the 2020 COVID-19 pandemic at a London university hospital.
P-261 Safety and effectiveness of tumor treating fields combined with sorafenib in preclinical models of hepatocellular carcinoma
Authors: S. Davidi, C. Tempel-Brami, M. Munster, K. Gotlib, E. Zeevi, R. Schneiderman, T. Voloshin, M. Giladi, U. Weinberg, Y. Palti
Journal: Annals of Oncology (2020)
Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial
Authors: David Rosmarin, Amit G Pandya, Mark Lebwohl, Pearl Grimes, Iltefat Hamzavi, Alice B Gottlieb, Kathleen Butler, Fiona Kuo, Kang Sun, Tao Ji, Michael D Howell, John E Harris
Journal: The Lancet (2020)
P-201 Neoadjuvant hypofractionated intensity-modulated radiotherapy with a simultaneous integrated boost combined with capecitabine in locally advanced rectal cancer
Authors: M. Vera Merino, D. Angel Schutte, B. López-Zamora, M. Almada, L. Suarez Villasmil, Y. Schworer, D. Venencia, S. Zunino
Journal: Annals of Oncology (2020)
Matt Morgan: Patients’ notes should be addressed to them
Authors: Matt Morgan
Journal: BMJ (2020)

Working in intensive care, I’m spared the pain (or joy) of writing clinic letters. In fact, most of the writing I do in my work is communication between healthcare professionals rather than directly with patients or their families. However, as with so many other things, covid-19 has changed this.

Relatives have often been unable to visit even critically ill loved ones during the covid-19 pandemic. As a result, the memories of tough conversations that I normally carry around with me have morphed from the distressed faces of family members into the rubber keys on my office phone. This collection of numbers is the …
Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources
Authors: Uros Kuzmanov, Erika Yan Wang, Rachel Vanderlaan, Da Hye Kim, Shin-Haw Lee, Sina Hadipour-Lakmehsari, Hongbo Guo, Yimu Zhao, Meghan McFadden, Parveen Sharma, Filio Billia, Milica Radisic, Anthony Gramolini, Andrew Emili
Journal: Nature Biomedical Engineering (2020)
Association of APEX1 and NUDT15 Polymorphisms with Mercaptopurine-Related Neutropenia in Pediatric Acute Lymphoblastic Leukemia
Authors: Hyery Kim, Heewon Seo, Yoomi Park, ByungJoo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Jae Won Yoo, Sung Han Kang, Kyung Nam Koh, Jong Jin Seo, Ho Joon Im, Ju Han Kim, Hyoung Jin Kang
Journal: Blood (2017)
Specific-oxygen-supply functionalized core-shell nanoparticles for smart mutual-promotion between photodynamic therapy and gambogic acid-induced chemotherapy
Authors: Lingfei Han, Yingming Wang, Xiaoxian Huang, Fulei Liu, Congyu Ma, Feng Feng, Jiguo Zhang, Wenyuan Liu, Wei Qu, Huan Pang, Jingwei Xue
Journal: Biomaterials (2020)
O-3 Efficacy and safety of entrectinib in NTRK fusion-positive gastrointestinal cancers: Updated integrated analysis of three clinical trials (STARTRK-2, STARTRK-1 and ALKA-372-001)
Authors: M. Patel, S. Siena, G. Demetri, R. Doebele, Y. Chae, P. Conkling, I. Garrido-Laguna, F. Longo, C. Rolfo, D. Sigal, A. Drilon, S. Liu, K. Goto, L. Bazhenova, S. Lonardi, F. Ciardiello, X. Huang, S. Osborne, A. Aziez, F. de Braud
Journal: Annals of Oncology (2020)
Abstract 16315: Transmembrane Stem Cell Factor Nanodiscs Enhance Revascularization in Ischemia and Have Less Mast Cell Activation
Authors: Eri Takematsu, Jeff Auster, Aditya Singh, Po-Chih Chen, Sophia Canga, Sanjana Srinath, Andre Degroot, Michael Sherman, Jeanne Stachowiak, Andrew K Dunn, Aaron Baker
Journal: Circulation (2019)

Introduction: The invasiveness of standard treatments for peripheral vascular disease (PVD) precludes their use in some patients and often does not provide a long term solution to continuing PVD. A...
Postischemic Administration of IL-1α Neutralizing Antibody Reduces Brain Damage and Neurological Deficit in Experimental Stroke
Authors: Luca Liberale, Nicole R. Bonetti, Yustina M. Puspitasari, Lena Schwarz, Alexander Akhmedov, Fabrizio Montecucco, Frank Ruschitzka, Jürg H. Beer, Thomas F. Lüscher, John Simard, Peter Libby, Giovanni G. Camici
Journal: Circulation (2020)
Eligibility for lipid lowering therapy based on AHA/ACC risk score, coronary artery calcification, and CVD events- national implications for the appropriate use of preventive pharmacotherapy: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Khurram Nasir, Márcio Sommer Bittencourt, Michael J Blaha, Matthew J Budoff, Ron Blankstein, Arthur Agatston, Christopher T Sibley, Leslee J Shaw, Roger Blumenthal, Harlan M Krumholz
Journal: Circulation (2014)
P-130 Short course pelvic radiotherapy for localized and oligometastatic rectal adenocarcinoma: The Mayo Clinic experience
Authors: S. Lee, N. Yu, B. Laughlin, M. Haddock, J. Ashman, K. Merrell, W. Rule, M. Neben Wittich, K. Mathis, A. Merchea, J. Hubbard, T. Bekaii-Saab, D. Ahn, Z. Jin, A. Mahipal, D. Etzioni, N. Mishra, S. Krishnan, C. Hallemeier, T. Sio
Journal: Annals of Oncology (2020)
Endomyocardial Biopsy Characterization of Heart Failure With Preserved Ejection Fraction and Prevalence of Cardiac Amyloidosis
Authors: Virginia S. Hahn, Lisa R. Yanek, Joban Vaishnav, Wendy Ying, Dhananjay Vaidya, Yi Zhen Joan Lee, Sarah J. Riley, Vinita Subramanya, Emily E. Brown, C. Danielle Hopkins, Sandra Ononogbu, Kira Perzel Mandell, Marc K. Halushka, Charles Steenbergen, Avi Z. Rosenberg, Ryan J. Tedford, Daniel P. Judge, Sanjiv J. Shah, Stuart D. Russell, David A. Kass, Kavita Sharma
Journal: JACC Heart Failure (2020)