tbuckley/cabot-search huggingface dataset:
Targeting BCL10 by small peptides for the treatment of B cell lymphoma
Authors: Wei Bao, Chenxia Sun, Xiaochen Sun, Miaoxia He, Haolan Yu, Wenfen Yan, Fuping Wen, Liang Zhang, Chenghua Yang
Journal: Theranostics (2020)

Rationale: Constitutive activation of the NF-κB signalling pathway plays a pivotal role in the pathogenesis of activated B cell-like diffuse large B-cell lymphomas (ABC-DLBCLs), the most aggressive and chemoresistant form of DLBCL. In ABC-DLBCLs, the CARMA1-BCL10 (CB) complex forms a filamentous structure and functions as a supramolecular organizing centre (CB-SMOC) that is required for constitutive NF-κB activation, making it an attractive drug target for ABC-DLBCL treatment. However, a pharmaceutical approach targeting CB-SMOC has been lacking. Here, we developed Bcl10 peptide inhibitors (BPIs) that specifically target the BCL10 filamentation process. Methods: Electron microscopy and immunofluorescence imaging were used to visualize the effect of the BPIs on the BCL10 filamentation process. The cytotoxicity of the tested BPIs was evaluated in DLBCL cell lines according to cell proliferation assays. Different in vitro experiments (pharmacokinetics, immunoprecipitation, western blotting, annexin V and PI staining) were conducted to determine the functional mechanisms of the BPIs. The in vivo therapeutic effect of the BPIs was examined in different xenograft DLBCL mouse models. Finally, Ki67 and TUNEL staining and histopathology analysis were used to evaluate the antineoplastic mechanisms and systemic toxicity of the BPIs. Results: We showed that these BPIs can effectively disrupt the BCL10 filamentation process, destabilize BCL10 and suppress NF-κB signalling in ABC-DLBCL cells. By examining a panel of DLBCL cell lines, we found that these BPIs selectively repressed the growth of CB-SMOC-dependent DLBCL cells by inducing apoptosis and cell cycle arrest. Moreover, by converting the BPIs to acquire a D-retro inverso (DRI) configuration, we developed DRI-BPIs with significantly improved intracellular stability and unimpaired BPI activity. These DRI-BPIs selectively repressed the growth of CB-SMOC-dependent DLBCL tumors in mouse xenograft models without eliciting discernible adverse effects. Conclusion: We developed novel BPIs to target the BCL10 filamentation process and demonstrated that targeting BCL10 by BPIs is a potentially safe and effective pharmaceutical approach for the treatment of ABC-DLBCL and other CB-SMOC-dependent malignancies.
LBA17 ASCENT: A randomized phase III study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in patients (pts) with previously treated metastatic triple-negative breast cancer (mTNBC)
Authors: A. Bardia, S.M. Tolaney, D. Loirat, K. Punie, M. Oliveira, H.S. Rugo, A. Brufsky, K. Kalinsky, J. Cortés, J. O'Shaughnessy, V.C. Dieras, L.A. Carey, L. Gianni, M. Piccart, S. Loibl, D. Goldenberg, Q. Hong, M.S. Olivo, L.M. Itri, S.A. Hurvitz
Journal: Annals of Oncology (2020)
Balancing the evidence for guidelines: lessons from the NICE abdominal aortic aneurysm guidance—an essay by Bruce Campbell
Authors: Bruce Campbell
Journal: BMJ (2020)

The saga of the National Institute for Health and Care Excellence’s abdominal aortic aneurysm guideline was a long and uncomfortable chapter in NICE history. But the conflict provides insights into balancing disparate types of evidence, writes <b>Bruce Campbell</b>
Drug Reimbursement Regulation in 6 Peer Countries
Authors: Ezekiel J. Emanuel, Cathy Zhang, Aaron Glickman, Emily Gudbranson, Sarah S. P. DiMagno, John W. Urwin
Journal: JAMA Internal Medicine (2020)

The US has nearly 4.5% of the world's population but accounts for more than 40% of global drug spending. With the upcoming 2020 election, a top priority of many voters is to better control drug prices and reform the pharmaceutical market. In this Special Communication, the drug price mechanisms and government regulations used in 6 representative peer countries are evaluated: Australia, France, Germany, Norway, Switzerland, and the United Kingdom. Drug price regulation is compared with that currently used in the US. Eight key lessons from the regulations used in these countries and which elements are incorporated into the bills currently making their way through the US Congress are evaluated (2 from the US House of Representatives and 1 from the US Senate). None of these bills is as systemic or comprehensive in its drug pricing mechanisms and regulations as the schemes in the other countries.
Medical school places: balancing quality, clinical need, and supporting students
Authors: Joshua L Davies
Journal: BMJ (2020)

I welcomed the news that medical school places will remain uncapped for the 2020 entry period with reticence.1 Almost all hospitals have revamped rotas to increase the number of doctors directly involved in patient care in response to covid-19. This has provided a glimpse of what could be. Wards have been well staffed, and colleagues have been close at hand to support each other. This …
1310P VinMetAtezo: Phase II trial of metronomic oral vinorelbine (MOV) with atezolizumab (ATZ) for recurrent stage IV NSCLC (GFPC*04-18)**
Authors: A. Vergnenegre, I. Monnet, C. Ricordel, A. Bizieux, R. Gervais, M. Bernardi, A-M. Chiappa, F. Guisier, S. Hominal, G. Le Garff, H. Berard, C. Locher Genty, C. Chouaid, G. Robinet
Journal: Annals of Oncology (2020)
Intense Increased 18F-FDG Uptake of Masticator Muscles After Cocaine Use
Authors: Pierre Meneret, Xavier Palard-Novello, Cécile Cuvilliers, Antoine Girard, Clémence Pontoizeau
Journal: Clinical Nuclear Medicine (2020)

Abstract 18 F-FDG is the most widely used PET tracer worldwide. Before the examination, recommendations are given to patients to avoid muscular activities, with the goal to limit 18 F-FDG uptake in muscles. Here, we report the case of a 36-year-old man with Hodgkin disease referred to our department to perform an 18 F-FDG PET/CT for immunotherapy assessment. The PET images showed a homogeneous, symmetric, and very intense uptake of the masticatory muscles. The medical examination exhibited a trismus, and the patient revealed to have been using cocaine 15 minutes before injection of 18 F-FDG.
915MO Long-term outcomes from KEYNOTE-048: Pembrolizumab (pembro) alone or with chemotherapy (pembro+C) vs EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)
Authors: R. Greil, D. Rischin, K.J. Harrington, D. Soulières, M. Tahara, G. de Castro, A. Psyrri, N. Baste, P. Neupane, Å. Bratland, T. Fuereder, B.G.M. Hughes, R. Mesia, N. Ngamphaiboon, T. Rordorf, W.Z. Wan Ishak, J. Lin, R.F. Swaby, B. Gumuscu, B. Burtness
Journal: Annals of Oncology (2020)
LBA46 Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: Final results regarding distant metastasis-free survival from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial
Authors: A.M.M. Eggermont, C.U. Blank, M. Mandala', G.V. Long, V. Atkinson, S. Dalle, A.M. Haydon, A. Meshcheryakov, A. Khattak, M. Carlino, S. Sandhu, S. Puig Sarda, P.A. Ascierto, A.C.J. van Akkooi, C. Krepler, N. Ibrahim, S.I. Marreaud, M. Kicinski, S. Suciu, C. Robert
Journal: Annals of Oncology (2020)
1138P Delayed immune-related adverse events (irAEs) on anti-PD1-based therapy
Authors: C.N. Owen, X. Bai, T. Quah, S. Lo, S. Callaghan, C. Martínez-Vila, P. Bhave, I. Reijers, C.L. Gerard, S. Aspelagh, W. Xu, S.J. Welsh, S. Sandhu, J. Mangana, J.L. McQuade, P.A. Ascierto, L. Zimmer, D.B. Johnson, C. Lebbé, A.M. Menzies
Journal: Annals of Oncology (2020)

IrAEs typically occur within 4 months of starting anti-PD1-based therapy (anti-PD1 +/- anti-CTLA4), but there are isolated reports of delayed irAEs (onset >12 months after commencement). This study describes the incidence, nature and management of delayed irAE in melanoma patients (pts). Pts from 20 centres with delayed irAEs were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma pts treated with anti-PD1-based therapy and surviving >1yr. irAE onset, clinical features, management and outcomes were examined. 122 pts developed a total of 144 delayed irAEs (23 after initial combination anti-PD-1 with anti-CTLA-4); with an estimated incidence of 5.7% (95% CI 4.3-7.3, 57/999 pts at sites with complete data). The median duration of therapy was 17.7 months (range 0.7-56.0), and median onset of delayed irAE was 16.3 months (range 12.0-53.2). 74% (90 pts) were on anti-PD1 at irAE onset, 12% (15 pts) were <3 months from last dose, 14% (17 pts) were >3 months from last dose of anti-PD1. The most common delayed irAEs were colitis, rash and pneumonitis (Table); 16% (19 pts) had multiple delayed irAEs, 39% (56 irAEs) were ≥G3. Steroids were required in 66% (81 pts), as well as an additional immunosuppressive agent in 23% (28 pts). There were 2 irAE-related deaths; encephalitis with onset during anti-PD1 and a multiple organ-irAE (colon, liver, kidney, lung and haem irAE) with onset 11.4 months after ceasing anti-PD1. Early irAEs (<12 months) had also occurred in 60% (73 pts), affecting a different organ to delayed irAEs in 86% (63 pts).Table: 1138PDelayed irAETotal patientsG1/G2G3/G4G5N (%) requiring systemic corticosteroidsN (%) requiring additional immunosuppressionTOTAL no pts with 144 irAE1227446281 (66%)28 (23%)Colitis31 (22%)1318029 (94%)13 (42%)Rash26 (18%)22407 (27%)1 (4%)Pneumonitis18 (13%)162017 (94%)0 (0%)Rheumatological14 (10%)11309 (64%)7 (50%)Hepatitis12 (8%)210010 (83%)2 (17%)Neurological10 (7%)3618 (80%)3 (30%)Hypophysitis7 (5%)5200 (0%)0 (0%)Renal7 (5%)1607 (100%)3 (43%)Other19 (13%)15405 (26%)1 (5%) Open table in a new tab Delayed irAEs occur in a small but relevant subset of pts, are often different to previous irAE, high grade, difficult to manage and can lead to death. Delayed irAEs mostly occur in pts still receiving anti-PD1, such that the risks of irAE need to be weighed against the benefits of continuing treatment in responding pts beyond 1 year, however pts who stopped treatment remained at risk for developing delayed irAE.
642P Role of free testosterone serum levels during salvage chemotherapy with carboplatin plus weekly docetaxel in patients with docetaxel-refractory, metastatic castration-resistant prostate cancer (mCRPC)
Authors: C.W.M. Reuter, S. Brunotte, P. Ivanyi, P. Kappler, M. Morgan
Journal: Annals of Oncology (2020)
1854P A randomized-controlled trial to evaluate the effect of reduced dose olanzapine on nausea/vomiting and addition of aprepitant on vomiting in patients receiving highly emetogenic chemotherapy
Authors: A. Sharma, S. Saldanha, D. Lokanatha, L. Jacob, M.C. Sureshbabu, K.N. Lokesh, A. Rudresha, L.K. Rajeev, K. Sharma
Journal: Annals of Oncology (2020)
317P Updated results from the Canadian sub-population of the phase IIIb CompLEEment-1 ribociclib + letrozole HR+ HER2- advanced breast cancer trial
Authors: N. Califaretti, C. Ferrario, E. Warner, A.A. Joy, S.K.L. Chia, J. Wu, J.P. Zarate, L. Menon-Singh, R.A. Leite, S. Haftchenary, S.R. Perri, S.F. Dent
Journal: Annals of Oncology (2020)
Single-Cell Genomics Reveals a Novel Cell State During Smooth Muscle Cell Phenotypic Switching and Potential Therapeutic Targets for Atherosclerosis in Mouse and Human
Authors: Huize Pan, Chenyi Xue, Benjamin J. Auerbach, Jiaxin Fan, Alexander C. Bashore, Jian Cui, Dina Y. Yang, Sarah B. Trignano, Wen Liu, Jianting Shi, Chinyere O. Ihuegbu, Erin C. Bush, Jeremy Worley, Lukas Vlahos, Pasquale Laise, Robert A. Solomon, Edward S. Connolly, Andrea Califano, Peter A. Sims, Hanrui Zhang, Mingyao Li, Muredach P. Reilly
Journal: Circulation (2020)

Background: Smooth muscle cells (SMCs) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration, and transdifferentiation into other cell types. Yet how SMCs contribute to the pathophysiology of atherosclerosis remains elusive. Methods: To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. We also performed cell biology experiments on isolated SMC-derived cells, conducted integrative human genomics, and used pharmacological studies targeting SMC-derived cells both in vivo and in vitro. Results: We found that SMCs transitioned to an intermediate cell state during atherosclerosis, which was also found in human atherosclerotic plaques of carotid and coronary arteries. SMC-derived intermediate cells, termed “SEM” cells (stem cell, endothelial cell, monocyte), were multipotent and could differentiate into macrophage-like and fibrochondrocyte-like cells, as well as return toward the SMC phenotype. Retinoic acid (RA) signaling was identified as a regulator of SMC to SEM cell transition, and RA signaling was dysregulated in symptomatic human atherosclerosis. Human genomics revealed enrichment of genome-wide association study signals for coronary artery disease in RA signaling target gene loci and correlation between coronary artery disease risk alleles and repressed expression of these genes. Activation of RA signaling by all-trans RA, an anticancer drug for acute promyelocytic leukemia, blocked SMC transition to SEM cells, reduced atherosclerotic burden, and promoted fibrous cap stability. Conclusions: Integration of cell-specific fate mapping, single-cell genomics, and human genetics adds novel insights into the complexity of SMC biology and reveals regulatory pathways for therapeutic targeting of SMC transitions in atherosclerotic cardiovascular disease.
245P Breast cancer in young women (BCYW): Clinical impact of diagnosis in asymptomatic patients
Authors: M. Mendez Garcia, J. Sánchez Gonzalez, M. Blanco Clemente, B. Nunez Garcia, M.C. Vega Carrasco, C. Alfaro Autor, B. De la Puente Orteu, M. Martínez Cutillas, R. Aguado Noya, M. López Valcárcel, M. Provencio Pulla, B. Cantos Sánchez de Ibarguen
Journal: Annals of Oncology (2020)
Origin and Evolution of the Gene Family of Proteinaceous Pheromones, the Exocrine Gland-Secreting Peptides, in Rodents
Authors: Yoshihito Niimura, Mai Tsunoda, Sari Kato, Ken Murata, Taichi Yanagawa, Shunta Suzuki, Kazushige Touhara
Journal: Molecular Biology and Evolution (2020)

Abstract The exocrine-gland secreting peptide (ESP)gene family encodes proteinaceous pheromones that are recognized by the vomeronasal organ in mice. For example, ESP1 is a male pheromone secreted in tear fluid that regulates socio-sexual behavior, and ESP22 is a juvenile pheromone that suppresses adult sexual behavior. The family consists of multiple genes and has been identified only in mouse and rat genomes. The coding region of a mouse ESP gene is separated into two exons, each encoding signal and mature sequences. Here, we report the origin and evolution of the ESP gene family. ESP genes were found only in the Muridea and Cricetidae families of rodents, suggesting a recent origin of ESP genes in the common ancestor of murids and cricetids. ESP genes show a great diversity in number, length, and sequence among different species as well as mouse strains. Some ESPs in rats and golden hamsters are expressed in the lacrimal gland and the salivary gland. We also found that a mature sequence of an ESP gene showed overall sequence similarity to the α-globin gene. The ancestral ESP gene seems to be generated by recombination of a retrotransposed α-globin gene with the signal-encoding exon of the CRISP2 gene located adjacent to the ESP gene cluster. This study provides an intriguing example of molecular tinkering in rapidly evolving species-specific proteinaceous pheromone genes.
Public Awareness of Invasive Fungal Diseases — United States, 2019
Authors: Kaitlin Benedict, Noelle Angelique M. Molinari, Brendan R. Jackson
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

1 = <$5,000; 2 = $5,000 to $7,499; 3 = $7,500 to $9,999; 4 = $10,000 to $12,499; 5 = $12,500 to $14,999; 6
Bioengineering strategies for the treatment of peripheral arterial disease
Authors: Cui Li, Oliver Kitzerow, Fujiao Nie, Jingxuan Dai, Xiaoyan Liu, Mark A. Carlson, George P. Casale, Iraklis I. Pipinos, Xiaowei Li
Journal: Bioactive Materials (2020)

Peripheral arterial disease (PAD) is a progressive atherosclerotic disorder characterized by narrowing and occlusion of arteries supplying the lower extremities. Approximately 200 million people worldwide are affected by PAD. The current standard of operative care is open or endovascular revascularization in which blood flow restoration is the goal. However, many patients are not appropriate candidates for these treatments and are subject to continuous ischemia of their lower limbs. Current research in the therapy of PAD involves developing modalities that induce angiogenesis, but the results of simple cell transplantation or growth factor delivery have been found to be relatively poor mainly due to difficulties in stem cell retention and survival and rapid diffusion and enzymolysis of growth factors following injection of these agents in the affected tissues. Biomaterials, including hydrogels, have the capability to protect stem cells during injection and to support cell survival. Hydrogels can also provide a sustained release of growth factors at the injection site. This review will focus on biomaterial systems currently being investigated as carriers for cell and growth factor delivery, and will also discuss biomaterials as a potential stand-alone method for the treatment of PAD. Finally, the challenges of development and use of biomaterials systems for PAD treatment will be reviewed.
Immunohistochemistry or Molecular Analysis: Which Method Is Better for Subtyping Craniopharyngioma?
Authors: Noriaki Fukuhara, Takeo Iwata, Naoko Inoshita, Katsuhiko Yoshimoto, Masanobu Kitagawa, Hirokazu Fukuhara, Keita Tatsushima, Mitsuo Yamaguchi-Okada, Akira Takeshita, Junko Ito, Yasuhiro Takeuchi, Shozo Yamada, Hiroshi Nishioka
Journal: Endocrine Pathology (2020)
Prevalence of mucocutaneous manifestations in 666 patients with COVID‐19 in a field hospital in Spain: oral and palmoplantar findings
Authors: A. Nuno‐Gonzalez, P. Martin‐Carrillo, K. Magaletsky, M.D. Martin Rios, C. Herranz Mañas, J. Artigas Almazan, G. García Casasola, E. Perez Castro, A. Gallego Arenas, A. Mayor Ibarguren, M. Feito Rodríguez, B. Lozano Masdemont, M. Beato, E. Ruiz Bravo, P. Oliver, M.D. Montero Vega, P. Herranz Pinto
Journal: British Journal of Dermatology (2020)

Prevalence of mucocutaneous
Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020
Authors: Sarah A. Mbaeyi, Catherine H. Bozio, Jonathan Duffy, Lorry G. Rubin, Susan Hariri, David S. Stephens, Jessica R. MacNeil
Journal: MMWR Recommendations and Reports (2020)

This report compiles and summarizes all recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United States. As a comprehensive summary and update of previously published recommendations, it replaces all previously published reports and policy notes. This report also contains new recommendations for administration of booster doses of serogroup B meningococcal (MenB) vaccine for persons at increased risk for serogroup B meningococcal disease. These guidelines will be updated as needed on the basis of availability of new data or licensure of new meningococcal vaccines. ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination with MenACWY for persons aged ≥2 months at increased risk for meningococcal disease caused by serogroups A, C, W, or Y, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor (e.g., eculizumab [Soliris] or ravulizumab [Ultomiris]); persons who have anatomic or functional asplenia; persons with human immunodeficiency virus infection; microbiologists routinely exposed to isolates of Neisseria meningitidis; persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroups A, C, W, or Y; persons who travel to or live in areas in which meningococcal disease is hyperendemic or epidemic; unvaccinated or incompletely vaccinated first-year college students living in residence halls; and military recruits. ACIP recommends MenACWY booster doses for previously vaccinated persons who become or remain at increased risk.In addition, ACIP recommends routine use of MenB vaccine series among persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor; persons who have anatomic or functional asplenia; microbiologists who are routinely exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroup B. ACIP recommends MenB booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends a MenB series for adolescents and young adults aged 16-23 years on the basis of shared clinical decision-making to provide short-term protection against disease caused by most strains of serogroup B N. meningitidis.
737P Synchronous metastatic renal cell carcinoma (mRCC) treated with nivolumab and ipilimumab (N+I) and the primary tumour (PT) in place
Authors: A. Meerveld-Eggink, N. Graafland, S. Wilgenhof, J.V. van Thienen, M. Grant, B.E. Szabados, Y. Abu-Ghanem, E. Boleti, C.U. Blank, J.B.A.G. Haanen, T.B. Powles, A. Bex
Journal: Annals of Oncology (2020)
Covid-19: Glitch leaves users unable to link test results to new contact tracing app
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Covid-19: Glitch leaves users unable to link test results to new contact tracing app Gareth IacobucciThousands of people who had tests for covid-19 in NHS hospitals and Public Health England (PHE) laboratories were unable to share their results with the NHS's new contact tracing app for England after it went live last week.
644P BRCA2 status and intraductal [IDC] and cribriform [CRIB] histologic variants: Partners in prostate cancer (PC)?
Authors: N. Romero Laorden, C. Llacer Perez, E. Castro Marcos, D.C. Salles, R. Lozano Mejorada, H. Thorne, I.M. Aragon, F. Lopez Campos, J. Rubio Briones, A.M. Gutierrez Pecharromán, J.D. Prieto, M.I. Pacheco, T. Garces, F. Zambrana, J. Mateo, P.P. Lopez-Casas, S. Sandhu, E.S. Antonarakis, D. Olmos Hidalgo, T. Lotan
Journal: Annals of Oncology (2020)