tbuckley/cabot-search huggingface dataset:
Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function
Authors: Yu Ding, Yongwen Zhou, Ping Ling, Xiaojun Feng, Sihui Luo, Xueying Zheng, Peter J Little, Suowen Xu, Jianping Weng
Journal: Theranostics (2021)

As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by "biochemical injury", ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), krüppel-like factor 4 (KLF4) and krüppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.
1027TiP A phase Ib study of CM24 in combination with nivolumab in adults with advanced solid tumors, followed by a phase IIa study of CM24 in combination with nivolumab in NSCLC, and in combination with nivolumab and nab-paclitaxel in pancreatic cancer
Authors: E. Borazanci, M.N. Al Hallak, J.P. Eder, T. Golan, S. Pant, R. Perets, G. Markel, M. Schickler, H. Reuveni, L. Jin, B. Liang
Journal: Annals of Oncology (2021)
512O Interim results from a phase II study of the ATR inhibitor ceralasertib in ARID1A-deficient and ARID1A-intact advanced solid tumor malignancies
Authors: R. Aggarwal, S. Umetsu, M. Dhawan, J. Grabowsky, J. Carnevale, M. Howell, L. Wilch, J. Chapman, E. Alvarez, S. Calabrese, S. Smith, N. Shah, E. Dean, P. Munster, E. Collisson
Journal: Annals of Oncology (2021)
Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes
Authors: Sushree S. Sahoo, Victor B. Pastor, Charnise Goodings, Rebecca K. Voss, Emilia J. Kozyra, Amina Szvetnik, Peter Noellke, Michael Dworzak, Jan Starý, Franco Locatelli, Riccardo Masetti, Markus Schmugge, Barbara De Moerloose, Albert Catala, Krisztián Kállay, Dominik Turkiewicz, Henrik Hasle, Jochen Buechner, Kirsi Jahnukainen, Marek Ussowicz, Sophia Polychronopoulou, Owen P. Smith, Oksana Fabri, Shlomit Barzilai, Valerie de Haas, Irith Baumann, Stephan Schwarz-Furlan, Jan Starý, Barbara De Moerloose, Krisztián Kallay, Owen Smith, Valérie De Haas, Gudrun Gohring, Charlotte Niemeyer, Karin Nebral, Ingrid Simonitsch-Kluppp, Pascale De Paepe, Nadine Van Roy, Vit Campr, Zuzana Zemanova, Erik Clasen-Linde, Tine Plesner, Brigitte Schlegelberger, Martina Rudelius, Kalliopi Manola, Kalliopi Stefanaki, Judit Csomor, Hajnalka Andrikovics, David Betts, Maureen O’Sullivan, Yaniv Zohar, Marta Jeison, Rita De Vito, Francesco Pasquali, Jadwiga Maldyk, Olga Haus, Helena Alaiz, Paula Kjollerstrom, Luis Mascarenhas de Lemos, Ivana Bodova, Martin Čermák, Lukas Plank, Barbara Gazic, Marko Kavcic, Helena Podgornik, Margarita Llavador Ros, Jose Cervera, Carole Gengler, Joelle Tchinda, Berna Beverloo, Roos Leguit, Marena R. Niewisch, Martin G. Sauer, Birgit Burkhardt, Peter Lang, Peter Bader, Rita Beier, Ingo Müller, Michael H. Albert, Roland Meisel, Ansgar Schulz, Gunnar Cario, Pritam K. Panda, Julius Wehrle, Shinsuke Hirabayashi, Marta Derecka, Robert Durruthy-Durruthy, Gudrun Göhring, Ayami Yoshimi-Noellke, Manching Ku, Dirk Lebrecht, Miriam Erlacher, Christian Flotho, Brigitte Strahm, Charlotte M. Niemeyer, Marcin W. Wlodarski
Journal: Nature Medicine (2021)
657MO Antibiotic (ATB) therapy and outcome from nivolumab (N) in metastatic renal cell carcinoma (mRCC) patients (pts): Results of the GETUG-AFU 26 NIVOREN multicentric phase II study
Authors: L. Derosa, C. Alves Costa Silva, C. Dalban, E. Colomba, S. Negrier, C.M. Chevreau, G. Gravis, S.M. Oudard, B. Laguerre, P. Barthelemy, D. Borchiellini, M. Gross-Goupil, L. Geoffrois, F. Rolland, A. Thiery-Vuillemin, F. Joly, S. Ladoire, F. Tantot, B. Escudier, L. Albiges
Journal: Annals of Oncology (2021)
418P Upfront primary tumour resection (UPTR) and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Authors: M. Benavides, A. Gómez-España, P. García-Alfonso, C. García, J.M. Vieitez, B. Massuti Sureda, F. Rivera, M.J. Safont Aguilera, A. Abad Esteve, M. Granja Ortega, M. Valladares-Ayerbes, A. Carrato Mena, E. González-Flores, L. Robles, A. Salud Salvia, V. Alonso, C. Montagut Viladot, E. Asensio-Martinez, E. Díaz-Rubio, E. Aranda Aguilar
Journal: Annals of Oncology (2021)
1534P Patterns of care and outcomes of NTRK-fusion positive sarcomas: A retrospective and prospective cases series
Authors: A. Dufresne, L. Lebellec, M. Karanian, D. Pissaloux, F. Tirode, N. Corradini, K. Rughoo, P.A. Cassier, P. Meeus, M.P. Sunyach, F. Gouin, I.L. Ray-Coquard, J-Y. Blay, N. Penel, B. Mehdi
Journal: Annals of Oncology (2021)
Nuclear IL-33 as a growth and survival agent within basal cells
Authors: Harold A. Chapman
Journal: Journal of Clinical Investigation (2021)

IL-33 is a well-studied cytokine that resides normally within nuclei but can be released by cell damage or stress to then signal via a single receptor widely expressed on immune cells to promote host resistance and type 2 allergic immunity. In this issue of the JCI, Wu et al. used a well-established model of mouse Sendai viral infection to show that IL-33 was induced in distal lung airway epithelium, specifically in cell-cycling basal cells. IL-33 induced cell-cycling basal cells to expand and migrate into the alveolar compartment, presumably to restore barrier function. However, restoring barrier function with airway-derived cells may also result in persistent alveolar metaplasia. Surprisingly, nuclear IL-33 in this system acted cell autonomously, independently of release and conventional ST2 (IL1RL1) receptor signaling. The findings uncover a signaling role for nuclear IL-33 in viral activation of mouse basal cells and add to the well-known "alarmin" function of IL-33.
Prospective Cohort Study of Pre- and Postdiagnosis Obesity and Endometrial Cancer Survival
Authors: Renée L Kokts-Porietis, Jessica McNeil, Andria R Morielli, Linda S Cook, Kerry S Courneya, Christine M Friedenreich
Journal: JNCI Journal of the National Cancer Institute (2021)

Disease-free survival (DFS) and overall survival (OS) associations with anthropometric measures of obesity and changes in these exposures remain unknown among endometrial cancer survivors.Endometrial cancer survivors diagnosed between 2002 and 2006 completed direct anthropometric measurements and self-reported lifetime weight history during in-person interviews approximately 4 months after diagnosis (peridiagnosis) and approximately 3 years after diagnosis (follow-up). Participants were followed-up until death or March 20, 2019. Cox proportional regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for body mass index (BMI), weight, waist circumference, and waist-hip ratio with DFS and OS. Statistical tests were 2-sided.A total of 540 and 425 cancer survivors were assessed peridiagnosis and follow-up, respectively. During the median 14.2 years of follow-up (range = 0.3-16.5 years), 132 participants had a recurrence and/or died (DFS), with 111 deaths overall (OS). Reduced DFS was noted with greater recalled weight 1 year before diagnosis (HR = 1.88, 95% CI = 1.15 to 3.07), BMI 1 year before diagnosis (HR = 1.88, 95% CI = 1.09 to 3.22), and measured peridiagnosis BMI (HR = 2.04, 95% CI = 1.18 to 3.53). Measured peridiagnosis waist circumference of at least 88 cm was associated with decreased DFS (HR = 1.94, 95% CI = 1.24 to 3.03) and OS (HR = 1.90, 95% CI = 1.16 to 3.13). A twofold decrease in DFS and OS was associated with a BMI of at least 5% or weight change from 1 year before diagnosis to peridiagnosis. No associations were observed for the assessment during follow-up.One-year before- and peridiagnosis anthropometric measures of obesity were associated with reduced survival among endometrial cancer survivors. Anthropometric changes from 1 year before to peridiagnosis may provide an important indication of future survival in this population.
999P NPC patients with post-RT EBV clearance show a higher frequency of peripheral CD8 T-cells expressing chemo-attractant receptors at baseline and during radiation therapy
Authors: S. Mahajan, A. Oostvogels, H.E. Balcioglu, A. Chan, K.W. Lo, E.P. Hui, B.B.Y. Ma, R. Debets
Journal: Annals of Oncology (2021)
Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression
Authors: Julia Dahlhoff, Hannah Manz, Tim Steinfatt, Julia Delgado-Tascon, Elena Seebacher, Theresa Schneider, Amy Wilnit, Zeinab Mokhtari, Paula Tabares, David Böckle, Leo Rasche, K. Martin Kortüm, Manfred B. Lutz, Hermann Einsele, Andreas Brandl, Andreas Beilhack
Journal: Leukemia (2021)

Abstract Multiple myeloma remains a largely incurable disease of clonally expanding malignant plasma cells. The bone marrow microenvironment harbors treatment-resistant myeloma cells, which eventually lead to disease relapse in patients. In the bone marrow, CD4 + FoxP3 + regulatory T cells (Tregs) are highly abundant amongst CD4 + T cells providing an immune protective niche for different long-living cell populations, e.g., hematopoietic stem cells. Here, we addressed the functional role of Tregs in multiple myeloma dissemination to bone marrow compartments and disease progression. To investigate the immune regulation of multiple myeloma, we utilized syngeneic immunocompetent murine multiple myeloma models in two different genetic backgrounds. Analyzing the spatial immune architecture of multiple myeloma revealed that the bone marrow Tregs accumulated in the vicinity of malignant plasma cells and displayed an activated phenotype. In vivo Treg depletion prevented multiple myeloma dissemination in both models. Importantly, short-term in vivo depletion of Tregs in mice with established multiple myeloma evoked a potent CD8 T cell- and NK cell-mediated immune response resulting in complete and stable remission. Conclusively, this preclinical in-vivo study suggests that Tregs are an attractive target for the treatment of multiple myeloma.
1847P Professional standing of young medical oncologists in Spain during COVID-19 pandemic: A nationwide survey by the Spanish Society of Medical Oncology (SEOM) +MIR Section
Authors: V. Pacheco-Barcia, D.A. Sanchez, B. Obispo, A. Quilez, A. Sesma, P. JimEnez Labaig, D. Paez, T. Quintanar Verduguez, M. Sánchez Cánovas, N. Tarazona, A. Fernandez Montes, E. Felip, A. Rodríguez-Lescure, M.E. Elez Fernandez
Journal: Annals of Oncology (2021)
896P Long-responders to ICI in R/M-HNSCC: A retrospective multicentric French cohort
Authors: M. Lasserre, L. Muratori, S.B. Esma, G. Marret, S. Salas, C. Borel, J-P. Delord, S. Le Nagat, F. Clatot, C. Evrard, F. Rolland, C. Even, C. Le Tourneau, A. Daste
Journal: Annals of Oncology (2021)
Tuning Hydrogels by Mixing Dynamic Cross‐Linkers: Enabling Cell‐Instructive Hydrogels and Advanced Bioinks
Authors: Francis L. C. Morgan, Julia Fernández‐Pérez, Lorenzo Moroni, Matthew B. Baker
Journal: Advanced Healthcare Materials (2021)

Rational design of hydrogels that balance processability and extracellular matrix (ECM) biomimicry remains a challenge for tissue engineering and biofabrication. Hydrogels suitable for biofabrication techniques, yet tuneable to match the mechanical (static and dynamic) properties of native tissues remain elusive. Dynamic covalent hydrogels possessing shear-thinning/self-healing (processability) and time-dependent cross-links (mechanical properties) provide a potential solution, yet can be difficult to rationally control. Here, the straightforward modular mixing of dynamic cross-links with different timescales (hydrazone and oxime) is explored using rheology, self-healing tests, extrusion printing, and culture of primary human dermal fibroblasts. Maintaining a constant polymer content and cross-linker concentration, the stiffness and stress relaxation can be tuned across two orders of magnitude. All formulations demonstrate a similar flow profile after network rupture, allowing the separation of initial mechanical properties from flow behavior during printing. Furthermore, the self-healing nature of hydrogels with high hydrazone content enables recyclability of printed structures. Last, a distinct threshold for cell spreading and morphology is observed within this hydrogel series, even in multi-material constructs. Simple cross-linker mixing enables fine control and is of general interest for bioink development, targeting viscoelastic properties of specific cellular niches, and as an accessible and flexible platform for designing dynamic networks.
DR Congo: WHO staff abused women and girls in Ebola outbreak, says “harrowing” independent report
Authors: Jacqui Wise
Journal: BMJ (2021)

Sexual exploitation and abuse, including rape and demands of sex in return for jobs, were committed by World Health Organization employees during the 2018-20 Ebola outbreak in the Democratic Republic of the Congo, an independent report has concluded.1

WHO’s director general, Tedros Adhanom Ghebreyesus, said that the 35 page report made for “harrowing reading” and apologised to victims, describing the findings as “inexcusable.” Speaking at a press conference, he said, “We must have zero tolerance for sexual exploitation and abuse, and zero tolerance for inaction against it.”

An independent commission was established after press reports of alleged sexual exploitation and abuse by WHO staff responding to the country’s 10th Ebola outbreak. The review team heard testimony from 63 women and 12 men aged 13-43 with an average age of around 20. The commission said that this was not an exhaustive list of alleged victims and that it …
1045P Comparison between first-line target therapy and immunotherapy in different prognostic categories of BRAF mutant metastatic melanoma patients
Authors: R. Marconcini, P. Fava, None F. de Rosa, M. De Tursi, E.T. Tanda, F. Consoli, G. Targato, N. Pimpinelli, F. Morgese, M. Bersanelli, M.G. Tucci, M. Saponara, A. Cortellini, M. Ocelli, R. Morganti, S. Manacorda, S. Bazzurri, A. Nuzzo, M. Ferrari, A. Falcone
Journal: Annals of Oncology (2021)
1082P Phase I study of ripretinib, a broad-spectrum KIT and PDGFRA inhibitor, in patients with KIT-mutated or KIT-amplified melanoma
Authors: F. Janku, S. Bauer, K. Shoumariyeh, R.L. Jones, A. Spreafico, J. Jennings, C. Psoinos, J. Meade, R. Ruiz-Soto, P. Chi
Journal: Annals of Oncology (2021)
Targeting mutant p53 for cancer therapy: direct and indirect strategies
Authors: Jiahao Hu, Jiasheng Cao, Win Topatana, Sarun Juengpanich, Shijie Li, Bin Zhang, Jiliang Shen, Liuxin Cai, Xiujun Cai, Mingyu Chen
Journal: Journal of Hematology & Oncology (2021)

TP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification of compounds capable of restoring/reactivating wild-type p53 functions or eliminating mutant p53. Treatments that directly target mutant p53 are extremely structure and drug-species-dependent. Due to the mutation of wild-type p53, multiple survival pathways that are normally maintained by wild-type p53 are disrupted, necessitating the activation of compensatory genes or pathways to promote cancer cell survival. Additionally, because the oncogenic functions of mutant p53 contribute to cancer proliferation and metastasis, targeting the signaling pathways altered by p53 mutation appears to be an attractive strategy. Synthetic lethality implies that while disruption of either gene alone is permissible among two genes with synthetic lethal interactions, complete disruption of both genes results in cell death. Thus, rather than directly targeting p53, exploiting mutant p53 synthetic lethal genes may provide additional therapeutic benefits. Additionally, research progress on the functions of noncoding RNAs has made it clear that disrupting noncoding RNA networks has a favorable antitumor effect, supporting the hypothesis that targeting noncoding RNAs may have potential synthetic lethal effects in cancers with p53 mutations. The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53. Additionally, the possibility of noncoding RNAs acting as synthetic lethal targets for mutant p53 will be discussed.
1611P Health-related quality of life, vaccine uptake and immune response among cancer patients undergoing treatment during the COVID-19 pandemic
Authors: J.C. Figueiredo, N. Merin, U. Ihenacho, O. Hamid, A.E. Hendifar, R. Vescio, R. Paquette, R.B. Natale, J. Darrah, R. Basho, H. McArthur, N. Nguyen, N. Punwani, E. Herrera, S. Cheng, S-J. Salvy, G. Datta, R. Figlin, A. Merchant, K.L. Reckamp
Journal: Annals of Oncology (2021)
Digital and technological innovation in vector-borne disease surveillance to predict, detect, and control climate-driven outbreaks
Authors: Caitlin Pley, Megan Evans, Rachel Lowe, Hugh Montgomery, Sophie Yacoub
Journal: The Lancet Planetary Health (2021)

Vector-borne diseases are particularly sensitive to changes in weather and climate. Timely warnings from surveillance systems can help to detect and control outbreaks of infectious disease, facilitate effective management of finite resources, and contribute to knowledge generation, response planning, and resource prioritisation in the long term, which can mitigate future outbreaks. Technological and digital innovations have enabled the incorporation of climatic data into surveillance systems, enhancing their capacity to predict trends in outbreak prevalence and location. Advance notice of the risk of an outbreak empowers decision makers and communities to scale up prevention and preparedness interventions and redirect resources for outbreak responses. In this Viewpoint, we outline important considerations in the advent of new technologies in disease surveillance, including the sustainability of innovation in the long term and the fundamental obligation to ensure that the communities that are affected by the disease are involved in the design of the technology and directly benefit from its application.
In patients with acute HF and iron deficiency, IV ferric carboxymaltose improved quality of life at 4 to 24 wk
Authors: Anthony A. Donato, Jared Green
Journal: Annals of Internal Medicine (2021)

Source Citation Jankowska EA, Kirwan BA, Kosiborod M, et al. The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study. Eur Heart J. 2021;42:3011-20. 34080008
259P Weekly ladiratuzumab vedotin monotherapy for metastatic triple-negative breast cancer
Authors: M. Tsai, H.S. Han, A.J. Montero, K.H. Tkaczuk, H. Assad, L. Pusztai, S.A. Hurvitz, S.T. Wilks, J.M. Specht, R. Nanda, M. Mita, J. O'Shaughnessy, I.E. Krop, D. Medgyesy, J. Abraham, S. Modi, H. Li, S. Wu, P.M. Garfin, H.A. Burris
Journal: Annals of Oncology (2021)
600P Final results of phase I/II trial of fractionated dose 177Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC)
Authors: S.T. Tagawa, M. Sun, O. Sartor, C. Thomas, A.M. Molina, C.N. Sternberg, D.M. Nanus, J. Osborne, N. Bander
Journal: Annals of Oncology (2021)
720TiP Phase I/II study of ipilimumab plus nivolumab (IPI-NIVO) combined with sacituzumab govitecan in patients with metastatic cisplatin-ineligible urothelial carcinoma
Authors: R.K. Jain, J. Chahoud, M. Chatwal, Y. Kim, J. Dhillon, A. Vosoughi, C. Araujo, R. Li, J. Zhang, G.P. Sonpavde
Journal: Annals of Oncology (2021)
原位置ハイブリッド形成法分析によりIgA腎症(IGAN)の予後を予測できる可能性
Authors: Miyazaki M, Tsukasaki S, Koji T, Abe K, Ozono Y, Harada T, Nakane Pk, Yagame M, Endoh M, Sakai H, Kohno S
Journal: Journal of the American Society of Nephrology (1997)
1329P A single-arm, open-label, multi-center, phase I study of HA121-28 in patients with advanced solid tumors
Authors: H. Zhao, X. Wei, Y. Huang, Y. Yang, W. Fang, Y. Ma, L. Chen, D. Chen, F. Wang, R. Peng, Q. Liu, R. Xu
Journal: Annals of Oncology (2021)
Diabetes and Obesity Bias: Are We Intensifying the Pharmacological Treatment in Patients With and Without Obesity With Equity?
Authors: Janine Alessi, Giovana B. de Oliveira, Isadora Nunes Erthal, Julia Belato Teixeira, Gabriela D.L.G. Scherer, Eduarda Herscovitz Jaeger, Josiane Schneiders, Guilherme H. Telo, Beatriz D. Schaan, Gabriela H. Telo
Journal: Diabetes Care (2021)
Hydrogen-bonded silicene nanosheets of engineered bandgap and selective degradability for photodynamic therapy
Authors: Deliang Xu, Han Lin, Wujie Qiu, Min Ge, Zhixin Chen, Chenyao Wu, Yanling You, Xiangyu Lu, Chenyang Wei, Jianjun Liu, Xiang Guo, Jianlin Shi
Journal: Biomaterials (2021)
1470P Oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence
Authors: T.R. Heumann, M. Baretti, E. Sugar, J. Durhman, S. Liden, T. Miles, T.Y. Lopez-Vidal, J. Leatherman, A. Sharma, N. Ahuja, C.D. Weekes, P.J. O'Dwyer, D.K. Monga, K.A. Reiss Binder, N. Azad
Journal: Annals of Oncology (2021)