tbuckley/cabot-search huggingface dataset:
Abstract PHB02: Impact of genetic diversity on the growth of human-derived xenografts
Authors: Jennifer Sargent, Roberto Cartagena, Stephanie Trowbridge, Steven Munger, Muneer Hasham
Journal: Cancer Research (2020)

Abstract The generation of human patient-derived xenograft (hPDX) models, and efficacy testing on human cell-derived xenografts (hCDX) or hPDX, are usually performed on a single mouse genetic background. Emerging evidence suggests that host genetic background underlies the variability in xenograft establishment as well as tumor response to drugs. Here we show two approaches, a genetic and a chemical one, on human-derived xenografts as proof of concept to show that xenografting can be done in genetic diverse mice and growth kinetics is different depending on the strain of the mice. The genetic approach is to use Rag1-/- mice for xenografts—Rag1-/- mice are immunodeficient and accept human cells. We found that the growth kinetics of a well-characterized hCDX is unequivocally distinct in three genetically diverse strains. The chemical approach is to use 2-deoxy glucose (2DG) to dampen the immune system in order to reduce graft rejection. We found that the growth kinetics and engraftment acceptability rates of a well-characterized hPDX were highly unique in eight genetically distinct outbred mice treated with 2DG. These findings provide proof of concept that xenografting can be conducted in genetically diverse mice. Development of these novel platforms will provide the genetic diversity necessary for the growth of any type of tumor, expanding the PDX platform to sustain cancers that have previously failed to xenograft. This abstract is also being presented as Poster B33. Citation Format: Jennifer Sargent, Roberto Cartagena, Stephanie Trowbridge, Steven Munger, Muneer Hasham. Impact of genetic diversity on the growth of human-derived xenografts [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr PHB02.
Adjuvant vs Salvage Radiation Therapy for High-Risk Prostate Cancer Following Radical Prostatectomy
Authors: Emily MacDuffie, Anthony V. D’Amico
Journal: JAMA Oncology (2020)

This Viewpoint examines the results of 3 randomized clinical trials that compared therapy with adjuvant radiation and salvage radiation in men with high-risk prostate cancer who have undergone radical prostatectomy.
Accrual of Atherosclerotic Vascular Events in a Multicenter Inception Systemic Lupus Erythematosus Cohort
Authors: Murray B. Urowitz, Dafna D. Gladman, Vernon Farewell, Jiandong Su, Juanita Romero-Diaz, Sang-Cheol Bae, Paul R. Fortin, Jorge Sanchez‐Guerrero, Ann Elaine Clarke, Sasha Bernatsky, Caroline Gordon, John G. Hanly, Daniel J. Wallace, David A. Isenberg, Anisur Rahman, Joan T. Merrill, Ellen Ginzler, Graciela S. Alarcón, W. Winn Chatham, Michelle A. Petri, Ian N. Bruce, Munther A. Khamashta, Cynthia Aranow, Mary Anne Dooley, Susan Manzi, Rosalind Ramsey‐Goldman, Ola Nived, Andreas Jönsen, Kristján Steinsson, Asad A. Zoma, Guillermo Ruiz-Irastorza, S. Sam Lim, Kenneth C. Kalunian, Murat Ỉnanç, Ronald van Vollenhoven, Manuel Ramos‐Casals, Diane L. Kamen, Soren Jacobsen, Christine A. Peschken, Anca Askanase, Thomas Stoll
Journal: Arthritis & Rheumatology (2020)

In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE.A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient-years, and univariable and multivariable relative risk regression models.Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow-up visit after enrollment, for a total of 13,666 patient-years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32-0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55-10.30]) and a body mass index of >40 kg/m2 (HR 2.74 [95% CI 1.04-7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17-9.27], P < 0.001).The prevalence of AVEs and the rate of AVE accrual demonstrated in the present study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors.
Abstract B14: Engineering a long-term in vitro model of breast cancer tumor resistance for high-throughput predictive drug screening
Authors: Rachel Weathered, Ruolan Zhou, Melody A. Swartz
Journal: Cancer Research (2020)

Abstract Solid tumors often show high levels of heterogeneity, making targeted therapeutics especially challenging. In breast cancer, for example, the primary cancer type may be eradicated with targeted therapy, but the minority subclones that are drug resistant can emerge as the new majority clones. Here, we present an in vitro model for long-term culture of ex vivo tumors (e.g., from biopsies) that maintain the tumor microenvironment such that tumors can be dramatically reduced with drugs yet maintained to observe long-term drug resistance. Our in vitro “avatars” (“ivitars”) utilize perfused 3D cultures in a high-throughput, robust, and easily maintained format. We demonstrate in vivo relevance with heterogeneous tumors composed of human breast cancer cell lines MCF-7 and LCC9, with sublines that are tamoxifen sensitive or resistant, in combination with stromal cells. Our results indicate that stromal cells, extracellular matrix components, and relevant biophysical stimuli such as fluid flow in the tumor microenvironment enhance tumor resistance to tamoxifen, even in tamoxifen-sensitive tumor cells. Together, our results suggest that the model can be used as a robust and high-throughput system for studying tumor resistance and will be further investigated for use in patient-specific testing. Citation Format: Rachel Weathered, Ruolan Zhou, Melody A. Swartz. Engineering a long-term in vitro model of breast cancer tumor resistance for high-throughput predictive drug screening [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr B14.
The World of Clinical Trial Development Post COVID-19: Lessons Learned from a Global Pandemic
Authors: Fatima Karzai, Ravi A. Madan, William L. Dahut
Journal: Clinical Cancer Research (2020)

Abstract The novel coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a global health threat (1). Patients with cancer are one of the most vulnerable populations. During this pandemic, clinical trial accrual to NCI studies has fallen dramatically. Investigators quickly turned to regulatory bodies to simplify treatment schedules, facilitate telemedicine, and decrease required data collection. Going forward, the oncology research community must use the lessons learned to focus on redesigning studies to ensure that critical scientific questions are answered safely while expanding access and increasing partnerships with community physicians. These changes will accelerate clinical progress while protecting our patients.
Impact of COVID-19 on surgical residency programs in Pakistan; A residents' perspective. Do programs need formal restructuring to adjust with the “new normal”? A cross-sectional survey study
Authors: Muhammad Osama, Farhan Zaheer, Hasham Saeed, Khadija Anees, Qirat Jawed, Sohaib Hasan Syed, Bashir A. Sheikh
Journal: International Journal of Surgery (2020)
The Project Baseline Health Study: a step towards a broader mission to map human health
Authors: Kristine Arges, Themistocles Assimes, Vikram Bajaj, Suresh Balu, Mustafa R. Bashir, Laura Beskow, Rosalia Blanco, Robert Califf, Paul Campbell, Larry Carin, Victoria Christian, Scott Cousins, Millie Das, Marie Dockery, Pamela S. Douglas, Ashley Dunham, Julie Eckstrand, Dominik Fleischmann, Emily Ford, Elizabeth Fraulo, John French, Sanjiv S. Gambhir, Geoffrey S. Ginsburg, Robert C. Green, Francois Haddad, Adrian Hernandez, John Hernandez, Erich S. Huang, Glenn Jaffe, Daniel King, Lynne H. Koweek, Curtis Langlotz, Yaping J. Liao, Kenneth W. Mahaffey, Kelly Marcom, William J. Marks, David Maron, Reid McCabe, Shannon McCall, Rebecca McCue, Jessica Mega, David Miller, Lawrence H. Muhlbaier, Rajan Munshi, L. Kristin Newby, Ezra Pak-Harvey, Bray Patrick-Lake, Michael Pencina, Eric D. Peterson, Fatima Rodriguez, Scarlet Shore, Svati Shah, Steven Shipes, George Sledge, Susie Spielman, Ryan Spitler, Terry Schaack, Geeta Swamy, Martin J. Willemink, Charlene A. Wong
Journal: npj Digital Medicine (2020)

The Project Baseline Health Study (PBHS) was launched to map human health through a comprehensive understanding of both the health of an individual and how it relates to the broader population. The study will contribute to the creation of a biomedical information system that accounts for the highly complex interplay of biological, behavioral, environmental, and social systems. The PBHS is a prospective, multicenter, longitudinal cohort study that aims to enroll thousands of participants with diverse backgrounds who are representative of the entire health spectrum. Enrolled participants will be evaluated serially using clinical, molecular, imaging, sensor, self-reported, behavioral, psychological, environmental, and other health-related measurements. An initial deeply phenotyped cohort will inform the development of a large, expanded virtual cohort. The PBHS will contribute to precision health and medicine by integrating state of the art testing, longitudinal monitoring and participant engagement, and by contributing to the development of an improved platform for data sharing and analysis.
Extracellular circulating DNA in diffuse large B- cell lymphoma patients: biological correlates and prognostic impact
Authors: Dino Dujmovic, Sandra Bašić Kinda, Pavle Roncevic, Antonela Samardzic, Ivo Radman, Vedrana Škaro, Gordan Lauc, Dubravčić Klara, Igor Aurer
Journal: HemaSphere (2018)
Abstract 16615: Sodium Nitrite Improves Left Ventricular Function During Heart Failure via Cytoprotective Signaling and Angiogenesis
Authors: Shashi Bhushan, Kazuhisa Kondo, David Polhemus, Chad Nicholson, Ya-Xiong Tao, Hui Huang, Toyoaki Murohara, Vasiliki V Georgiopoulou, John W Calvert, Javed Butler, David J Lefer
Journal: Circulation (2013)

Background: Nitric oxide (NO) bioavailability is reduced in the setting of heart failure. We have previously demonstrated that sodium nitrite ameliorates acute myocardial ischemia/reperfusion (MI/R...
Assessment and management of adults with asthma during the covid-19 pandemic
Authors: Thomas Beaney, David Salman, Tahseen Samee, Vincent Mak
Journal: BMJ (2020)

### What you need to know A 35 year old man contacts his general practice reporting a dry cough and increased shortness of breath for the past three days. He has a history of asthma, for which he uses an inhaled corticosteroid twice daily and is now using his salbutamol four times a day. Because of the covid-19 outbreak, he is booked in for a telephone consultation with a general practitioner that morning. Asthma is a condition commonly encountered in primary care, with over five million people in the UK prescribed active treatment.1 While seemingly a routine part of general practice, asthma assessment is a particular challenge in the context of the covid-19 pandemic, given the overlap in respiratory symptoms between the two conditions and the need to minimise face-to-face assessment. Over 1400 people died from asthma in 2018 in England and Wales,2 while analyses of non-covid-19 deaths during the covid-19 outbreak have shown an increase in deaths due to asthma,31 highlighting the need to distinguish the symptoms of acute asthma from those of covid-19 and manage them accordingly. This article outlines how to assess and manage adults with exacerbations of asthma in the context of the covid-19 outbreak (box 1). We focus on the features differentiating acute asthma from covid-19, the challenges of remote assessment, and the importance of corticosteroids in patients with an asthma exacerbation. Box 1 ### Asthma and covid-19: what does the evidence tell us? #### Are patients with asthma at higher risk from covid-19? Some studies, mostly from China, found … RETURN TO TEXT
Multistate Mumps Outbreak Originating from Asymptomatic Transmission at a Nebraska Wedding — Six States, August–October 2019
Authors: Matthew Donahue, Blake Hendrickson, Derek Julian, Nicholas Hill, Julie Rother, Samir Koirala, Joshua L. Clayton, Thomas Safranek, Bryan Buss
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In August 2019, 30 attendees at a Nebraska wedding developed mumps after being exposed to one asymptomatic index patient who was fully vaccinated according to Advisory Committee on Immunization Practices (ACIP) recommendations (1), resulting in a multistate outbreak. A public health investigation and response revealed epidemiologic links that extended from the index patient through secondary, tertiary, and quaternary patients and culminated in a measles-mumps-rubella (MMR) booster vaccination campaign in the local community where approximately half of the patients resided.
18F-NaF Uptake in Breast Cancer
Authors: Huipan Liu, Lin Liu, Wenhui Fu, Yue Chen
Journal: Clinical Nuclear Medicine (2020)

Abstract A 55-year-old woman with back pain underwent 18 F-NaF PET/CT study to evaluate bone metastases from newly diagnosed breast cancer. Multiple foci of increased tracer uptake indicating osteoblastic metastases were noted in cervical and thoracic vertebrae. Unexpectedly, breast cancer also revealed increased NaF activity.
Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): Impact of type of cancer therapy and COVID therapy on survival.
Authors: Leora Horn, Jennifer G. Whisenant, Valter Torri, Li-Ching Huang, Annalisa Trama, Luis G. Paz-Ares, Enriqueta Felip, Vera Pancaldi, Alessandro De Toma, Marcello Tiseo, Pilar Garrido, Carlo Genova, Jacques Cadranel, Olivier Michielin, Anne-Marie C. Dingemans, Jan P. Van Meerbeeck, Fabrice Barlesi, Heather A. Wakelee, Solange Peters, Marina Chiara Garassino
Journal: Journal of Clinical Oncology (2020)

LBA111 Background: Early reports on cancer patients infected with COVID-19 have suggested a high mortality rate compared to the general population. Patients with thoracic malignancies are considered high risk given their age, preexisting comorbidities, smoking, and pre-existing lung damage in addition to therapies administered to treat their illness. Method: We launched a global consortium to collect data on patients with thoracic malignancies diagnosed with COVID-19 infection to understand the impact on this patient population. Goals of this consortium are to provide data for guidance to oncology professionals on treating patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus. Results: As of April 23, 2020, a total of 295 patients across 59 centers and 9 countries have been entered; median age 68, 31% female, 79% current/former smokers, HTN and COPD most common comorbidities; 73% NSCLC, 14% SCLC, 4% meso and thymic, 49% patients with stage IV disease, majority on chemo or chemo-IO and 24% receiving RT. The use of IO or chemo-IO does not appear to impact risk of hospitalization, while treatment with TKI appears to be associated with a decreased risk of hospitalization. 73% patients required hospitalization, most common therapy given to treat COVID was antibiotics 67%, antivirals 33%, and steroids 30%. Conclusion: With an ongoing global pandemic of COVID-19 our data suggest that patients with thoracic malignancies are at high risk for hospitalization. Updated results to be presented will include impact on specific chemo-IO regimens and number of lines of therapy, which may impact hospitalization and risk of death as well as which therapies administered may impact survival in patients treated for COVID-19.
SAT0540 ONE-YEAR OUTCOMES AFTER RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS FROM CHECKPOINT INHIBITORS
Authors: E. Berard, T. Barnetche, L. Rouxel, C. Dutriaux, L. Dousset, S. Prey, M. Beylot-Barry, J. Seneschal, R. Veillon, C. Vergnenegre, A. Daste, C. Domblides, B. Sionneau, M. Gross-Goupil, A. Ravaud, E. Forcade, T. Schaeverbeke, M. Kostine
Journal: Annals of the Rheumatic Diseases (2020)

Background: Description and initial management of rheumatic immune-related adverse-events (irAEs) from cancer immunotherapies have been reported by several groups but to date, few studies have evaluated the long-term outcomes and management of rheumatic irAEs (1). Objectives: To describe the long-term management and assess the one-year outcomes of patients who experienced rheumatic immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICI). Methods: This was a single-centre prospective observational study including patients referred for musculoskeletal symptoms while treated with ICI. After baseline rheumatological evaluation defining the clinical entity presented, follow-up visits were organised according to the type and severity of irAE. At one year, persistence of irAE, ongoing treatment, as well as cancer outcomes were assessed. Results: 63 patients were included between September 2015 and June 2018. 24 patients (38%) presented with non-inflammatory musculoskeletal conditions managed with short-term symptomatic treatment and did not require specific follow-up. 39 patients (62%) experienced inflammatory manifestations, mimicking either rheumatoid arthritis (RA, n=19), polymyalgia rheumatica (PMR, n=16), psoriatic arthritis (PsA, n=3) and one flare of a preexisting axial spondyloarthritis. Overall, 32 patients (82%) received systemic glucocorticoids, with a median rheumatic dosage of 15mg/day (range: 5-60mg/day). None of the patients had to permanently discontinue ICI therapy for rheumatic irAE. 20 patients (67%) were still receiving glucocorticoids at one year, with a median dosage of 5mg/day (range: 2-20mg/day). Glucocorticoids were more frequently discontinued for patients with RA-like condition (44%) than PMR-like condition (23%), but no other predictive factor of glucocorticoids withdrawal could be identified. At one year, overall survival and progression-free survival were comparable between patients who were still receiving glucocorticoids for rheumatic irAE and patients who have discontinued. Eight patients required csDMARDs. Conclusion: At one year, a majority of patients required long-term low-dose glucocorticoids for chronic rheumatic irAE, which seems not altering oncological control. References: [1]Braaten TJ, Brahmer JR, Forde PM, et al. Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation. Ann Rheum Dis. 2019 Sep 20. Disclosure of Interests: None declared
Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial
Authors: Jun Sato, Miyako Satouchi, Shoichi Itoh, Yusuke Okuma, Seiji Niho, Hidenori Mizugaki, Haruyasu Murakami, Yasuhito Fujisaka, Toshiyuki Kozuki, Kenichi Nakamura, Yukari Nagasaka, Mamiko Kawasaki, Tomoaki Yamada, Ryunosuke Machida, Aya Kuchiba, Yuichiro Ohe, Noboru Yamamoto
Journal: The Lancet Oncology (2020)
Progressive vasoconstriction with sequential thermal stimulation indicates vascular dysautonomia in sickle cell disease
Authors: Saranya Veluswamy, Payal Shah, Maha Khaleel, Wanwara Thuptimdang, Patjanaporn Chalacheva, John Sunwoo, Christopher C. Denton, Roberta Kato, Jon Detterich, John C. Wood, Richard Sposto, Michael C. K. Khoo, Lonnie Zeltzer, Thomas D. Coates
Journal: Blood (2020)
Dissecting miRNA facilitated physiology and function in human breast cancer for therapeutic intervention
Authors: Dipta Sengupta, Moonmoon Deb, Swayamsiddha Kar, Nibedita Pradhan, Sabnam Parbin, R. Kirtana, Suraj P. Singh, S.G. Suma, None Niharika, Ankan Roy, Saumen Manna, Priyanka Saha, Priyanka Chakraborty, Soumya Dash, Chahat Kausar, Samir Kumar Patra
Journal: Seminars in Cancer Biology (2020)
Abstract 12238: Effects of IL-1 Blockade With Anakinra on Blood Pressure, Systemic Vascular Resistance and Arterial Elastance in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of the Randomized, Double-blind, Placebo-controlled REDHART Study
Authors: Leo F Buckley, Justin M Canada, Cory R Trankle, Salvatore Carbone, Dinesh Kadariya, Hayley Billingsley, George F Wohlford, Antonio Abbate, Benjamin W Van Tassell
Journal: Circulation (2019)

Introduction: Hypotension limits guideline-directed neurohormonal blocker use in HFrEF. Interleukin (IL)-1 blockade with anakinra improves cardiorespiratory fitness and may prevent HF decompensatio...
Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study
Authors: Gilles Salles, Johannes Duell, Eva González Barca, Olivier Tournilhac, Wojciech Jurczak, Anna Marina Liberati, Zsolt Nagy, Aleš Obr, Gianluca Gaidano, Marc André, Nagesh Kalakonda, Martin Dreyling, Johannes Weirather, Maren Dirnberger-Hertweck, Sumeet Ambarkhane, Günter Fingerle-Rowson, Kami Maddocks
Journal: The Lancet Oncology (2020)
Maturation of nasal microbiota and antibiotic exposures during early childhood: a population-based cohort study
Authors: Y. Raita, L. Toivonen, L. Schuez-Havupalo, S. Karppinen, M. Waris, K.L. Hoffman, C.A. Camargo, V. Peltola, K. Hasegawa
Journal: Clinical Microbiology and Infection (2020)
GP who was suspended for risky prescribing is allowed to remove himself from the medical register
Authors: Clare Dyer
Journal: BMJ (2020)

A GP who was suspended from the UK medical register for eight months over clinical failings involving four patients, including two cases of risky prescribing, has been allowed to take himself off the register instead of applying to resume work.

Simon Caswell, 68, appeared before a review tribunal, which typically convenes near the end of a doctor’s suspension to consider their fitness to return to practice. Instead it considered his request for voluntary …