tbuckley/cabot-search huggingface dataset:
Finding a Voice for the Accidentally Unbefriended
Authors: Anita B. Major, Aanand D. Naik, Timothy W. Farrell
Journal: JAMA Internal Medicine (2021)

Finding a Voice for the Accidentally Unbefriended She experienced a slow decline over the last decade that was attributable to her dementia.She now needs assistance with all activities of daily living.Most days are consumed by agitation, including episodes of yelling out.Rare moments of lucidity and peace are reserved for loved ones whom she still recognizes in the familiarity of her home.Despite these symptoms, her life is safe and stable.She has family members and caregivers, with whom a coauthor (A.B.M.) collaborates as her physician.She has a voice and a story that still resonate because those who know her best are physically present.Then, the pandemic upended the delicate balance of her life when all of her caregivers, her husband, and finally she became ill from COVID-19.Vulnerable patients rely on the physical and emotional support of advocates, who are individuals with whom they have connections and who are especially important when critical decisions need to be made about their well-being.Isolating these vulnerable patients from their advocates was an unintended consequence of restricted visitation policies during the pandemic.When the patient described earlier entered the emergency department, hospital protocols prevented anyone from accompanying her inside.Yet, she is unable to provide a history or relate her story.In unfamiliar surroundings with all advocates being denied access, what will happen to her voice?The COVID-19 pandemic has exacerbated the problem of social isolation, especially among older adults with frailty. 1 Consequently, a new phenotype of incapacitated older adults without advocates, otherwise known as individuals who are "unbefriended" or "unrepresented," has emerged. 2 This new phenotype of vulnerable patients differs from the typical unbefriended patient in that they enjoy support from a loving family and dedicated caregivers at home.Despite this, they also end up losing their voices as hospitals struggle to prioritize the safety of the public's health and implement policies to protect others while isolating those most in need of familiar faces.As such, these patients become accidentally unbefriended during their hospital stay because of the pandemic.Advocates do much more than provide histories to clinicians and make difficult medical decisions on behalf of patients who lack the capacity to make these decisions.They also fill the gaps of basic, daily care that hospitals often cannot easily provide to older adults with cognitive impairment, such as taking extra time to accompany someone during a meal, helping to orient someone with delirium, and bringing comfort and familiarity to someone with dementia.However, during the COVID-19 pandemic, these seemingly insignificant tasks are now paramount and are extremely difficult to complete because of restricted visitor access.The patientcaregiver dyad that was emotionally and physically in-
Abstract 942: ErbB3 overexpression unleashed by miR-205 epigenetic silencing is a therapeutic target in glioblastoma
Authors: Francesca De Bacco, Francesca Orzan, Jessica Erriquez, Elena Casanova, Ludovic Barault, Raffaella Albano, Antonio D'Ambrosio, Viola Bigatto, Gigliola Reato, Monica Patané, Bianca Pollo, Geoffrey Kuesters, Carmine Dell'Aglio, Laura Casorzo, Serena Pellegatta, Gaetano Finocchiaro, Paolo M. Comoglio, Carla Boccaccio
Journal: Cancer Research (2021)

Abstract In glioblastoma (GBM), the most frequent and lethal brain tumor, targeted therapies suppressing commonly altered signaling pathways has remained so far disappointing. However, in selected patient subsets, specific genetic alterations can confer sensitivity to targeted agents. In this study, by generating an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, we identified a human GBM subset (around 9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation. This was driven by inheritable epigenetic or post-transcriptional silencing of the oncosuppressor miR-205 and sustained the malignant phenotype. Unexpectedly, ERBB3, known to be devoid of autonomous signaling properties, was overexpressed in the absence of the other members of the EGFR family, but behaved as a specific signaling platform for FGFRs. ERBB3/FGFR dimerization led to hyperactivation of the PI3K/AKT/mTOR pathway and consequent upregulation of glycolysis, oxidative metabolism and de novo fatty acid biosynthesis. Treatment with a specific antibody (MM121) preventing ERBB3 association with FGFR caused metabolic shutdown and consequent proliferative arrest and apoptosis induction in vitro. Moreover, experimental tumors regenerated through ERBB3 overexpressing stem-like cell transplantation reproduced the features of the original GBMs and, upon treatment with the anti-ERBB3 antibody, significantly regressed. These findings identify a subset of GBM patients where exploitation of an ERBB3-targeted therapy could be effective. Citation Format: Francesca De Bacco, Francesca Orzan, Jessica Erriquez, Elena Casanova, Ludovic Barault, Raffaella Albano, Antonio D'Ambrosio, Viola Bigatto, Gigliola Reato, Monica Patané, Bianca Pollo, Geoffrey Kuesters, Carmine Dell'Aglio, Laura Casorzo, Serena Pellegatta, Gaetano Finocchiaro, Paolo M. Comoglio, Carla Boccaccio. ErbB3 overexpression unleashed by miR-205 epigenetic silencing is a therapeutic target in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 942.
Abstract 10143: Mitochondrial Quality Control in Atg7-deficient Vsmc Apoe-/- Mice
Authors: Hripsime Nahapetyan, Anne-Valerie Cantero, Elisa Grousset, Manon Moulis, Meyer Elbaz, Wim Martinet, Cecile Vindis
Journal: Circulation (2019)

Vascular smooth muscle cells (VSMCs) are one of the main cellular determinants in arterial pathology and several evidence indicates that apoptosis of VSMCs is associated with features of high-risk/...
Abstract 2346: Prostate cancer castrate resistant progression usage of non-canonical androgen receptor signaling and ketone body fuel
Authors: Estefania Labanca, Juan Bizzotto, Jun Yang, Pablo Sanchis, Peter Shepherd, Alejandra Paez, Valeria Antico-Arciuch, Nicolas Anselmino, Sofia Lage-Vickers, Anh Hoang, Mark Tituts, Eleni Efstathiou, Javier Cotignola, Christopher Logothetis, Elba Vazquez, Nora Navone, Geraldine Gueron
Journal: Cancer Research (2021)

Abstract Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis. Using PCa patient-derived xenografts (PDXs) we assessed the metabolic changes after castration of tumor-bearing mice. We found that relapsed tumors had a significant increase in fatty acids and ketone body content compared with baseline. We confirmed that critical ketogenic/ketolytic enzymes (ACAT1, OXCT1, BDH1) were significantly augmented after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. Increased ACAT1 and OXCT1 was also observed for a subset of PCa patients that relapsed with low AR and ERG expression. These factors were associated with decreased biochemical relapse and progression free survival. In summary, our studies reveal the key metabolites fueling castration resistant progression in the context of a partial or complete loss of AR dependence. Citation Format: Estefania Labanca, Juan Bizzotto, Jun Yang, Pablo Sanchis, Peter Shepherd, Alejandra Paez, Valeria Antico-Arciuch, Nicolas Anselmino, Sofia Lage-Vickers, Anh Hoang, Mark Tituts, Eleni Efstathiou, Javier Cotignola, Christopher Logothetis, Elba Vazquez, Nora Navone, Geraldine Gueron. Prostate cancer castrate resistant progression usage of non-canonical androgen receptor signaling and ketone body fuel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2346.
Global projections of temperature-attributable mortality due to enteric infections: a modelling study
Authors: Paul L C Chua, Veronika Huber, Chris Fook Sheng Ng, Xerxes T Seposo, Lina Madaniyazi, Simon Hales, Alistair Woodward, Masahiro Hashizume
Journal: The Lancet Planetary Health (2021)

BackgroundMortality due to enteric infections is projected to increase because of global warming; however, the different temperature sensitivities of major enteric pathogens have not yet been considered in projections on a global scale. We aimed to project global temperature-attributable enteric infection mortality under various future scenarios of sociodemographic development and climate change.MethodsIn this modelling study, we generated global projections in two stages. First, we forecasted baseline mortality from ten enteropathogens (non-typhoidal salmonella, Shigella, Campylobacter, cholera, enteropathogenic Escherichia coli, enterotoxigenic E coli, typhoid, rotavirus, norovirus, and Cryptosporidium) under several future sociodemographic development and health investment scenarios (ie, pessimistic, intermediate, and optimistic). We then estimated the mortality change from baseline attributable to global warming using the product of projected annual temperature anomalies and pathogen-specific temperature sensitivities.FindingsWe estimated that in the period 2080–95, the global mean number of temperature-attributable deaths due to enteric infections could be as low as 6599 (95% empirical CI 5441–7757) under the optimistic sociodemographic development and climate change scenario, or as high as 83 888 (67 760–100 015) under the pessimistic scenario. Most of the projected temperature-attributable deaths were from shigellosis, cryptosporidiosis, and typhoid fever in sub-Saharan Africa and South Asia. Considerable reductions in the number of attributable deaths were from viral infections, such as rotaviral and noroviral enteritis, which resulted in net reductions in attributable enteric infection mortality under optimistic scenarios for Latin America and the Caribbean and East Asia and the Pacific.InterpretationTemperature-attributable mortality could increase under warmer climate and unfavourable sociodemographic conditions. Mitigation policies for limiting global warming and sociodemographic development policies for low-income and middle-income countries might help reduce mortality from enteric infections in the future.FundingJapan Society for the Promotion of Science, Japan Science and Technology Agency, and Spanish Ministry of Economy, Industry, and Competitiveness.
Safety but Limited Efficacy of Ensartinib in ROS1-Positive NSCLC: A Single-Arm, Multicenter Phase 2 Study
Authors: Xinghao Ai, Qiming Wang, Ying Cheng, Xiaoqing Liu, Lejie Cao, Jianhua Chen, Xiaorong Dong, Jianying Zhou, Yun Fan, Cheng Huang, Jiuwei Cui, Yan Wang, Gongyan Chen, Cuimin Ding, Beili Gao, Xingya Li, Ziping Wang, Helong Zhang, Lieming Ding, Yang Wang, Xiaobin Yuan, Hongke Cheng, Tao Wang, Shun Lu
Journal: Journal of Thoracic Oncology (2021)
The prevalence of nocturnal polyuria in the US: Results from the Epidemiology of Nocturnal Polyuria (EpiNP) study
Authors: K.S. Coyne, J.L.H.R. Bosch, C.R. Chapple, E.D. Bacci, J.C. Simeone, M. Rosenberg, E. Mueller, F.L. Andersson, K. Juul, B. Chughtai, J.P. Weiss
Journal: European Urology (2021)
Aneurysm rupture after choledochoduodenostomy with lumen-apposing metal stent: endoscopic ultrasound-guided stenting of the bile duct in an endoscopically blind situation due to massive bleeding
Authors: Jane-Rose Paccard, Thomas Lambin, Jérôme Rivory, Florian Rostain, Arnaud Thivolet, Pierre Lafeuille, Mathieu Pioche
Journal: Endoscopy (2021)

Choledochoduodenostomy is now an alternative treatment when endoscopic retrograde cholangiopancreatography fails to drain the bile duct [1] [2] [3]. However, the apposition stent can cause artery erosion leading to severe bleeding [4] [5].
Abstract 1046: Synergistic cytotoxic effect of sulfated glycolipid PG545 in combination with ATR inhibition in ovarian cancer cells
Authors: Yinan Xiao, Chaolin Deng, Ye Guan, Ling Jin, Upasana Ray, Prabhu Thirusangu, Julie Staub, Haotian Xu, Viji Shridhar
Journal: Cancer Research (2021)

Abstract Despite the advances in the molecular understanding of ovarian cancer (OC), improvements in therapy are still needed. PG545 is a highly sulfated small molecule and is currently in Phase I clinical investigation, which has shown promising antitumor activity in multiple tumor models, including ovarian, endometrial and pancreatic cancers. Ataxia telangiectasia and Rad3-related protein (ATR), plays a crucial role in maintaining genomic integrity by responding to a large spectrum of DNA damage, including double strand breaks (DSBs) that interfere with replication. Several ATR inhibitors have been developed, but resistance is likely to occur. This study aimed to investigate the potential synergistic effect of combining PG545 with ATR inhibition in OC. Proliferation and clonogenic assay showed that combination of PG545 with ATR shRNA or ATR inhibitor (ATRi; VE-822) synergistically decreased cell survival compared with single-agent treatments in two OC cell lines, OVCAR5 and OVCAR8 cells. PG545 monotherapy induced DNA damage, activated the ATR signaling pathways as well as the S and G2/M cell cycle checkpoints. The combination of PG545 and ATRi inhibited the phosphorylation of ATR and Chk1, induced γH2AX and lead to a marked increase in pan-nuclear γH2AX-positive cells. Moreover, ATRi diminished the cell cycle effects of PG545 and markedly enhanced PG545-induced apoptosis in OC cell lines. Taken together, our results indicate that the combination of PG545 with ATR inhibition may be promising options to be considered in future clinical trials of OC. Citation Format: Yinan Xiao, Chaolin Deng, Ye Guan, Ling Jin, Upasana Ray, Prabhu Thirusangu, Julie Staub, Haotian Xu, Viji Shridhar. Synergistic cytotoxic effect of sulfated glycolipid PG545 in combination with ATR inhibition in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1046.
Abstract 1207: Thymoquinone-based drug development targeting SUCLA2 loss in advanced prostate cancer
Authors: Chiaki Takahashi
Journal: Cancer Research (2021)

Abstract RB1 gene is often homozygously deleted or mutated in prostate adenocarcinomas following acquirement of castration resistance and/or metastatic ability. We found that SUCLA2 gene is frequently involved in the deletion of the RB1 gene region in advanced prostate cancer. SUCLA2 constitutes the β-subunit of succinate CoA ligase heterodimer that reversibly converts succinyl CoA into succinate. We sought the possibility that deletion of SUCLA2 gives rise to a metabolic vulnerability that could be targeted therapeutically. Indeed, we found a significant metabolic shift in SUCLA2-deleted prostate cancer cells, including lower mitochondrialrespiratory activity. By screening a number of libraries for compounds that induce cell death selectively in SUCLA2-deficient prostate cancer cells, we identified thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) and PMA (phorbol-12-myristate-13-acetate) from a natural compound library. Thymoquinone has been known for its anti-tumor efficacy. We examined the biological activity of a number of thymoquinone derivatives and synthesized chemical probes to identify molecular target of this agent. In this presentation, we will propose a new therapeutic approach to advanced prostate cancers. Citation Format: Chiaki Takahashi. Thymoquinone-based drug development targeting SUCLA2 loss in advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1207.
Infection Complications in Patients with Multiple Myeloma Treated with New-Drug Combinations Including Thalidomide.
Authors: Massimo Offidani, Agnese Savini, Laura Corvatta, Claudia Polloni, Silvia Gentili, Annamaria Brioni, Giuseppe Visani, Piero Galieni, Francesco Alesiani, Marino Brunori, Massimo Catarini, Anna Mele, Maurizio Burattini, Arduino Samori, Riccardo Centurioni, Nicola Blasi, Mario Ferranti, Paolo Fraticelli, Rita Rizzi, Pietro Leoni
Journal: Blood (2009)
Abstract 1696: Anti-tumor effects from simultaneous cancer and TAM targeting by 010DS-Zn
Authors: Jinhyuk Fred Chung
Journal: Cancer Research (2021)

Abstract Direct clearance of immune-suppressive Tumor Associated Macrophages (TAM) is a less-explored cancer therapeutic approach. We developed a novel folate-ligand guided zinc-peptide complex 010DS-Zn for selective induction of parthanatos in folate receptor overexpressing targets that include many solid and blood cancer types, in addition to M2-like macrophages. Consistent with known parthanatos mechanism, its in vitro mode-of-action (MOA) tested against 4T1 murine breast cancer cell was characterized by specific and rapid PARP-dependent AIF translocation into nucleus that executed massive DNA fragmentation. This in vitro/ex vivo cytotoxicity was found highly consistent against the 90 blood and solid patient-derived cancer types tested. Further in vivo MOA studies against aPD-1 responder and non-responder syngenic cancer models showed 010DS-Zn to be effective against both, albeit at increased dosage in the MDSC enriched tumors. In the aPD-1 responder cancer model CT26, 010DS-Zn demonstrated robust T-cell immune response initiation, which was enhanced upon co-treatment with aPD-1 mAb. Regardless of the tumor-response in vivo, 010DS-Zn treatment produced robust TAM-reduction activity in dose-dependent manners. Collectively, 010DS-Zn presents new cancer immunotherapeutic potentials for enabling previously inaccessible 2-combination therapies for targeting 3 layers of immune-evasion: Tregs, TAM, and MDSC. Furthermore, its ability to directly clear M2-like macrophages presents opportunities-worth-investigation for treating the M2-like macrophage-driven severe SARS-CoV-2 autoimmune syndromes or its post-recovery heart-damages. Citation Format: Jinhyuk Fred Chung. Anti-tumor effects from simultaneous cancer and TAM targeting by 010DS-Zn [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1696.
COVID-19 Vaccination Coverage Among Insured Persons Aged ≥16 Years, by Race/Ethnicity and Other Selected Characteristics — Eight Integrated Health Care Organizations, United States, December 14, 2020–May 15, 2021
Authors: Cassandra Pingali, Mehreen Meghani, Hilda Razzaghi, Mark J. Lamias, Eric Weintraub, Tat'Yana A. Kenigsberg, Nicola P. Klein, Ned Lewis, Bruce Fireman, Ousseny Zerbo, Joan Bartlett, Kristin Goddard, James Donahue, Kayla Hanson, Allison Naleway, Elyse O. Kharbanda, W. Katherine Yih, Jennifer Clark Nelson, Bruno J. Lewin, Joshua T.B. Williams, Jason M. Glanz, James A. Singleton, Suchita A. Patel
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

COVID-19 vaccination is critical to ending the COVID-19 pandemic.Members of minority racial and ethnic groups have experienced disproportionate COVID-19-associated morbidity and mortality (1); however, COVID-19 vaccination coverage is lower in these groups (2).CDC used data from CDC's Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020-May 15, 2021.Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson & Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine).Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020-May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated.As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%).Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%).Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%).Persons aged 18-24 years had the lowest * https://www.cdc.gov/vaccines/covid-19/info-by-product/clinicalconsiderations.htmlhttps://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/
Abstract 2428: NR4A1 ligands inhibits PSPC1 regulated EMT and stemness markers in breast, lung and liver cancer cells
Authors: Kumaravel Mohankumar, Rupesh Shrestha, Stephen Safe
Journal: Cancer Research (2021)

Abstract The orphan nuclear receptor 4A1 (Nur77, TR3, NR4A1) is highly expressed in solid tumors and is a negative prognostic factor for survival of breast, lung, and liver cancer patients (1) and ongoing studies in our laboratory show that NR4A1 is pro-oncogenic in multiple tumor types. We have also identified a series of bis-indole derived compounds including 1,1-bis(3'-indolyl)-1-(p-hydroxyphenyl) methane (DIM-C-pPhOH; CDIM8) that act as NR4A1 antagonists that inhibit pro-oncogenic NR4A1-regulated genes and pathways in multiple cancer cell lines (2). Mechanistic studies show that many of the NR4A1-regulated genes involve interactions of NR4A1 with gene promoter DNA or with Sp-bound to GC-rich sequences and similar mechanisms have previously been observed for steroid hormone and other nuclear receptors. Our studies have identified paraspeckle component 1 (PSPC1) as an NR4A1 regulated gene in breast, lung and liver cancer cells and PSPC1 gene expression and protein levels are suppressed after treatment with C-DIM/NR4A1 antagonists. PSPC1 promotes tumorigenesis, epithelial-to-mesenchymal transition (EMT), stemness and metastasis and is a master activator of pro-metastatic switches and a potential target for anti-metastatic drugs. Knockdown of PSPC1 downregulates EMT and stemness markers in breast, lung and liver cancer cells. The novel buttressed analog of CDIM8 (DIM-C-pPhOH-3-Br-5-OCF3) at a concentration of 10 uM downregulates PSPC1 expression and its downstream targets (Snail, Slug, Nanog, OCT4, SOX2, c-myc). Knockdown of NR4A1 or SP1 inhibits PSPC1 expression in MDA-MB-231, H1299 and SNU449 cell lines respectively. These results identify PSPC1 as a novel gene that regulates EMT and invasion in these cancer cells and NR4A1 is an upstream regulator of PSPC1 gene expression. Thus, NR4A1 ligands act as an antimetastatic mimic by inhibiting PSPC1 and the mechanism of PSPC1 regulation involves ligand induced interactions of NR4A1/SP1 with a GC-rich region of the PSPC1 gene promoter. References:1.Safe S, Jin UH, Hedrick E, Reeder A, Lee SO. Minireview: Role of orphan nuclear receptors in cancer and potential as drug targets. Mol Endocrinol. 2014;28(2):157-72. 2.Mohankumar K, Li X, Sridharan S, Karki K, Safe S. Nuclear receptor 4A1 (NR4A1) antagonists induce ROS-dependent inhibition of mTOR signaling in endometrial cancer. Gynecol Oncol. 2019; 154(1):218-227. Citation Format: Kumaravel Mohankumar, Rupesh Shrestha, Stephen Safe. NR4A1 ligands inhibits PSPC1 regulated EMT and stemness markers in breast, lung and liver cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2428.