tbuckley/cabot-search huggingface dataset:
Abstract 978: Magnolol induces apoptosis and inhibits metastasis via suppression of NF-κB activation in human bladder cancer
Authors: Sin-Rong Lee, Zhao-Lin Tan, Yuan Chang, I-Tsang Chiang, Fei-Ting Hsu
Journal: Cancer Research (2021)

Abstract Magnolol is a phenolic compound extracted from magnolia officinalis, and known as a common Chinese medicinal material used in the treatment of strokes, colds, etc. Magnolol has also recognized as an anti-inflammation agent which can downregulate several inflammation signals transduction. Several reports suggested that magnolol may also have anti-tumor potential in liver and colon cancer. Nevertheless, the regulatory mechanism of magnolol on apoptosis and NF-κB signaling in human bladder cancer has not been elucidated. Thus, the purpose of the study was to investigate the mechanism and therapeutic efficacy on bladder cancer. First of all, we used MTT assay to investigate the cytotoxicity induction after magnolol treatment in bladder cancer. Then, we used NF-κB translocation assay to evaluate whether the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was decreased after magnolol treatment. We also detected the apoptosis induction ability of magnolol on extrinsic/intrinsic apoptosis pathway. This study demonstrated that magnolol significantly triggered the accumulation at the sub-G1 phase, the loss of mitochondrial membrane potential, and the activation of cleaved caspase-3, -8 and -9. Further verify the effect of magnolol on the expression of anti-apoptotic related proteins, we performed Western blotting. Magnolol inhibited migration and invasion ability of bladder cancer were investigated by wound healing and invasion assay. Then, we performed Western blotting to detect whether magnolol may inhibit NF-κB-mediated downstream signaling that involving in anti-apoptosis and metastasis such as MCL-1 and MMP9 protein expression. Moreover, the reduction of Cyclin D1 protein expression was used to evaluate the inhibition of cell proliferation by magnolol. In sum, our result demonstrated that magnolol induced extrinsic and intrinsic apoptosis mechanism and inhibit invasion/migration ability of bladder cancer was associated with the inactivation of NF-κB. Citation Format: Sin-Rong Lee, Zhao-Lin Tan, Yuan Chang, I-Tsang Chiang, Fei-Ting Hsu. Magnolol induces apoptosis and inhibits metastasis via suppression of NF-κB activation in human bladder 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 978.
In adults and children, a rapid POC antigen test for COVID-19 (LumiraDx) had ≥97% sensitivity and specificity vs. RT-PCR
Authors: Thomas Fekete
Journal: Annals of Internal Medicine (2021)

Source CitationDrain PK, Ampajwala M, Chappel C, et al. A rapid, high-sensitivity SARS-CoV-2 nucleocapsid immunoassay to aid diagnosis of acute COVID-19 at the point of care: a clinical performance study. Infect Dis Ther. 2021;10:753-61 https://pubmed.ncbi.nlm.nih.gov/33629225/AbstractClinical Impact RatingsEmergency Med: Hospitalists: Infectious Disease: Public Health:
Outcomes after surgical treatment for urethral strictures in transgender men after genital gender-affirming surgery with urethral lengthening
Authors: F.P.W. de Rooij, F.R.M. Peters, B.L. Ronkes, W. Van Der Sluis, M. Al-Tamimi, R.J.A. Van Moorselaar, M.B. Bouman, G.L.S. Pigot
Journal: European Urology (2021)
Abstract 2295: SGK2, 14-3-3, and HUWE1 coordinately regulate the localization and stability of PTOV1
Authors: Katie L. Pennington, James Woods, Colin Muir, Colten M. McEwan, Pramoda S. Aththota Gamage, Riley J. Eastmond, Crissy M. Egbert, Tyler Heaton, Stephen R. Piccolo, Joshua L. Andersen
Journal: Cancer Research (2021)

Abstract PTOV1 is an oncogenic protein, initially identified in prostate cancer, that promotes proliferation, cell motility, and invasiveness. However, the mechanism of PTOV1 regulation is poorly understood. To understand these mechanisms, we identify 14-3-3 as a PTOV1 interactor and show that high levels of 14-3-3 expression, like PTOV1, correlate with prostate cancer progression. Further, we found that SGK2-mediated phosphorylation of PTOV1 is required for 14-3-3 binding. This phosphorylation occurs in a cell cycle-dependent manner and peaks in the G1 phase. Disruption of the PTOV1-14-3-3 interaction results in an accumulation of PTOV1 in the nucleus and a proteasome-dependent reduction in PTOV1 protein levels. To understand the effect of 14-3-3 on PTOV1 stability, we found that loss of 14-3-3 binding leads to an increase in PTOV1 binding to the E3 ubiquitin ligase HUWE1, which promotes proteasomal degradation of PTOV1. Conversely, our data suggest that 14-3-3 stabilizes PTOV1 protein by sequestering PTOV1 in the cytosol and inhibiting its interaction with HUWE1. Finally, our data suggest that stabilization of the 14-3-3-bound form of PTOV1 promotes PTOV1-mediated expression of cJun. Together, these data provide a first mechanism to understand the regulation of PTOV1 stability, localization, and function within the cell. Citation Format: Katie L. Pennington, James Woods, Colin Muir, Colten M. McEwan, Pramoda S. Aththota Gamage, Riley J. Eastmond, Crissy M. Egbert, Tyler Heaton, Stephen R. Piccolo, Joshua L. Andersen. SGK2, 14-3-3, and HUWE1 coordinately regulate the localization and stability of PTOV1 [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 2295.
Ex-vivo evaluation of intraurethral catheter balloon inflation pressures, urethral diametric strain and rupture thresholds in porcine and human specimens
Authors: S.M. Croghan, C.V. Cunnane, M.T. Walsh, E.M. Cunnane, N.F. Davis, J.E. Mulvihill, H.D. Flood
Journal: European Urology (2021)
Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis
Authors: Ryunosuke Saiki, Yukihide Momozawa, Yasuhito Nannya, Masahiro M. Nakagawa, Yotaro Ochi, Tetsuichi Yoshizato, Chikashi Terao, Yutaka Kuroda, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Atsushi Niida, Seiya Imoto, Koichi Matsuda, Takayuki Morisaki, Yoshinori Murakami, Yoichiro Kamatani, Shuichi Matsuda, Michiaki Kubo, Satoru Miyano, Hideki Makishima, Seishi Ogawa
Journal: Nature Medicine (2021)
Abstract 1828: AZD8853: A novel antibody targeting GDF15 for immunotherapy refractory tumors
Authors: Elaine Hurt, Suneetha Thomas, Kathy Mulgrew, Stephen Blackmore, James Moynihan, Fiona Cusdin, Roger Dodd, Peter Cariuk, Anna Sigurdardottir, Emily Brannigan, Claire Dobson, Rakesh Kumar, Mark Cobbold
Journal: Cancer Research (2021)

Abstract Immunotherapy has revolutionized patient care, however, the majority of patients with cancer still do not benefit from this treatment modality. This is due to many factors, including a complex tumor microenvironment (TME) that has too few functional effector cells and/or the presence of many inhibitory cells. Understanding how to remodel the TME to potentiate productive immunity against cancer cells is an active area of research. Growth and Differentiation Factor 15 (GDF-15) is a member of the TGF-beta superfamily that is overexpressed by many solid tumors and is implicated in dampening immune responses. The present study was aimed at understanding the role of GDF-15 in tumor immune biology. We show that GDF-15 can inhibit the differentiation and activation of human monocyte-derived dendritic cells (DCs) and prevent T cell activation. Furthermore blockade of GDF-15 by AZD8853, an anti-GDF15 monoclonal antibody, can restore these activities in vitro. Tumors derived from GDF15 knock-out syngeneic cell lines, Renca and MC-38, show 2-3 fold increases in T cells and activated DCs in the TME as compared to tumors derived from isogeneic parental cells. Treatment of mice with anti-GDF15 mAb leads to substantial anti-tumor activity in anti-PD-L1 refractory LL/2 and MBT2 syngeneic tumors with 50% of the animals showing complete tumor regressions. Coupled with this anti-tumor activity, we show that after 2 doses of anti-GDF15 mAb there is an increase in both activated T cells and DCs in the TME. Depletion of T cells, using anti-CD4 and anti-CD8, in mice ablates the anti-tumor activity observed with anti-GDF15 mAb treatment. These results suggest that inhibition of GDF15 by AZD8853 may be an attractive therapeutic strategy for patients with solid tumors that have high expression of GDF15. Citation Format: Elaine Hurt, Suneetha Thomas, Kathy Mulgrew, Stephen Blackmore, James Moynihan, Fiona Cusdin, Roger Dodd, Peter Cariuk, Anna Sigurdardottir, Emily Brannigan, Claire Dobson, Rakesh Kumar, Mark Cobbold. AZD8853: A novel antibody targeting GDF15 for immunotherapy refractory tumors [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 1828.
Prostate Specific Membrane Antigen (PSMA) PET/CT ligand uptake across histological sub-types of renal tumours
Authors: A. Tariq, A. Pearce, H. Rhee, P. Thomas, D. Pattison, S. Kyle, A. Navaratnam, N. Dunglison, R. Esler, J. Yaxley, M. Roberts
Journal: European Urology (2021)
Lymph node fibroblastic reticular cells steer immune responses
Authors: Lushen Li, Jing Wu, Reza Abdi, Christopher M. Jewell, Jonathan S. Bromberg
Journal: Trends in Immunology (2021)

Lymph nodes (LNs), where immune responses are initiated, are organized into distinctive compartments by fibroblastic reticular cells (FRCs). FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. Recent high-resolution transcriptional and histological analyses have enriched our knowledge of LN FRC genetic and spatial heterogeneities. Here, we summarize updated anatomic, phenotypic, and functional identities of FRC subsets, delve into topological and transcriptional remodeling of FRCs in inflammation, and illustrate the crosstalk between FRCs and immune cells. Discussing FRC functions in immunity and tolerance, we highlight state-of-the-art FRC-based therapeutic approaches for maintaining physiological homeostasis, steering protective immunity, inducing transplantation tolerance, and treating diverse immune-related diseases.
Air Pollution, Genetic Factors, and the Risk of Lung Cancer: A Prospective Study in the UK Biobank
Authors: Yanqian Huang, Meng Zhu, Mengmeng Ji, Jingyi Fan, Junxing Xie, Xiaoxia Wei, Xiangxiang Jiang, Jing Xu, Liang Chen, Rong Yin, Yuzhuo Wang, Juncheng Dai, Guangfu Jin, Lin Xu, Zhibin Hu, Hongxia Ma, Hongbing Shen
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Both genetic and environmental factors contribute to lung cancer, but the degree to which air pollution modifies the impact of genetic susceptibility on lung cancer remains unknown. Objectives: To investigate whether air pollution and genetic factors jointly contribute to incident lung cancer. Methods: We analyzed data from 455,974 participants (53% women) without previous cancer at baseline in the UK Biobank. The concentrations of particulate matter (PM) (PM ⩽2.5 μm in aerodynamic diameter [PM2.5], coarse PM between 2.5 μm and 10 μm in aerodynamic diameter [PMcoarse], and PM ⩽10 μm in aerodynamic diameter [PM10]), nitrogen dioxide (NO2), and nitrogen oxides (NOx) were estimated by using land-use regression models, and the association between air pollutants and incident lung cancer was investigated by using a Cox proportional hazard model. Furthermore, we constructed a polygenic risk score and evaluated whether air pollutants modified the effect of genetic susceptibility on the development of lung cancer. Measurements and Main Results: The results showed significant associations between the risk of lung cancer and PM2.5 (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.33-2.01; per 5 μg/m3), PM10 (HR, 1.53; 95% CI, 1.20-1.96; per 10 μg/m3), NO2 (HR, 1.10; 95% CI, 1.05-1.15; per 10 μg/m3), and NOx (HR, 1.13; 95% CI, 1.07-1.18; per 20 μg/m3). There were additive interactions between air pollutants and the genetic risk. Compared with participants with low genetic risk and low air pollution exposure, those with high air pollution exposure and high genetic risk had the highest risk of lung cancer (PM2.5: HR, 1.71; 95% CI, 1.45-2.02; PM10: HR, 1.77; 95% CI, 1.50-2.10; NO2: HR, 1.77; 95% CI, 1.42-2.22; NOx: HR, 1.67; 95% CI, 1.43-1.95). Conclusions: Long-term exposure to air pollution may increase the risk of lung cancer, especially in those with high genetic risk.
COVID-19 Vaccine Administration, by Race and Ethnicity — North Carolina, December 14, 2020–April 6, 2021
Authors: Charlene A. Wong, Shannon Dowler, Amanda Fuller Moore, Erin Fry Sosne, Hayley Young, Jessica D. Tenenbaum, Cardra E. Burns, Sydney Jones, Marina Smelyanskaya, Kody H. Kinsley
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

COVID-19 has disproportionately affected non-Hispanic Black or African American (Black) and Hispanic persons in the United States (1,2).In North Carolina during January-September 2020, deaths from COVID-19 were 1.6 times higher among Black persons than among non-Hispanic White persons (3), and the rate of COVID-19 cases among Hispanic persons was 2.3 times higher than that among non-Hispanic persons (4).During December 14, 2020-April 6, 2021, the North Carolina Department of Health and Human Services (NCDHHS) monitored the proportion of Black and Hispanic persons* aged ≥16 years who received COVID-19 vaccinations, relative to the population proportions of these groups.On January 14, 2021, NCDHHS implemented a multipronged strategy to prioritize COVID-19 vaccinations among Black and Hispanic persons.This included mapping communities with larger population proportions of persons aged ≥65 years among these groups, increasing vaccine allocations to providers serving these communities, setting expectations that the share of vaccines administered to Black and Hispanic persons matched or exceeded population proportions, and facilitating community partnerships.From December 14, 2020-January 3, 2021 to March 29-April 6, 2021, the proportion of vaccines administered to Black persons increased from 9.2% to 18.7%, and the proportion administered to Hispanic persons increased from 3.9% to 9.9%, approaching the population proportion aged ≥16 years of these groups (22.3% and 8.0%, respectively).Vaccinating communities most affected by COVID-19 is a national priority (5).Public health officials could use U.S. Census tract-level mapping to guide vaccine allocation, promote shared accountability for equitable distribution of COVID-19 vaccines with vaccine providers through data sharing, and facilitate community partnerships to support vaccine access and promote equity in vaccine uptake.On January 14, 2021, NCDHHS adopted an equitypromoting vaccination strategy that included both per capita and equity-based vaccine allocation, shared accountability, and community partnerships.Approximately 20% of COVID-19 vaccine doses were set aside for allocation informed by * Race and ethnicity were self-reported by vaccinated persons and recorded by health care providers in the NCDHHS COVID-19 Vaccination Management System (CVMS).Race and ethnicity were analyzed separately.Black persons were those who identified as being of Black race regardless of ethnicity.Hispanic persons were those who identified as being of Hispanic ethnicity regardless of race.
3D models’ use during robotic prostatectomy allows to reduce positive surgical margins rate
Authors: E. Checcucci, A. Pecoraro, S. De Cillis, D. Amparore, F. Piramide, A. Piana, G. Volpi, P. Alessio, M. Sica, S. Granato, S. Piscitello, B. Carbonaro, G. Cattaneo, M. Manfredi, C. Fiori, F. Porpiglia
Journal: European Urology (2021)
Analysis of Estimated and Measured Glomerular Filtration Rates and the CKD-EPI Equation Race Coefficient in the Chronic Renal Insufficiency Cohort Study
Authors: Chi-yuan Hsu, Wei Yang, Alan S. Go, Rishi V. Parikh, Harold I. Feldman
Journal: JAMA Network Open (2021)

This diagnostic/prognostic study examines the estimated glomerular filtration rates (eGFR) and iothalamate clearance glomerular filtration rates (iGFR) and the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation race coefficient in the Chronic Renal Insufficiency Cohort study.
The E3 Ubiquitin Ligase Ring Finger Protein 5 Ameliorates NASH Through Ubiquitin‐Mediated Degradation of 3‐Hydroxy‐3‐Methylglutaryl CoA Reductase Degradation Protein 1
Authors: Qin Yang, Xi Chen, Yanfang Zhang, Sha Hu, Fengjiao Hu, Yongping Huang, Tengfei Ma, Heng Hu, Han Tian, Song Tian, Yan‐Xiao Ji, Zhi‐Gang She, Peng Zhang, Xiao‐Jing Zhang, Yufeng Hu, Hailong Yang, Yufeng Yuan, Hongliang Li
Journal: Hepatology (2021)

Background and Aims NAFLD is the most prevalent chronic liver disease worldwide, but no effective pharmacological therapeutics are available for clinical use. NASH is the more severe stage of NAFLD. During this progress, dysregulation of endoplasmic reticulum (ER)–related pathways and proteins is one of the predominant hallmarks. We aimed to reveal the role of ring finger protein 5 (RNF5), an ER-localized E3 ubiquitin-protein ligase, in NASH and to explore its underlying mechanism. Approach and Results We first inspected the expression level of RNF5 and found that it was markedly decreased in livers with NASH in multiple species including humans. We then introduced adenoviruses for Rnf5 overexpression or knockdown into primary mouse hepatocytes and found that palmitic acid/oleic acid (PAOA)–induced lipid accumulation and inflammation in hepatocytes were markedly attenuated by Rnf5 overexpression but exacerbated by Rnf5 gene silencing. Hepatocyte-specific Rnf5 knockout significantly exacerbated hepatic steatosis, inflammatory response, and fibrosis in mice challenged with diet-induced NASH. Mechanistically, we identified 3-hydroxy-3-methylglutaryl CoA reductase degradation protein 1 (HRD1) as a binding partner of RNF5 by systematic interactomics analysis. RNF5 directly bound to HRD1 and promoted its lysine 48 (K48)–linked and K33-linked ubiquitination and subsequent proteasomal degradation. Furthermore, Hrd1 overexpression significantly exacerbated PAOA-induced lipid accumulation and inflammation, and short hairpin RNA–mediated Hrd1 knockdown exerted the opposite effects. Notably, Hrd1 knockdown significantly diminished PAOA-induced lipid deposition, and up-regulation of related genes resulted from Rnf5 ablation in hepatocytes. Conclusions These data indicate that RNF5 inhibits NASH progression by targeting HRD1 in the ubiquitin-mediated proteasomal pathway. Targeting the RNF5–HRD1 axis may provide insights into the pathogenesis of NASH and pave the way for developing strategies for NASH prevention and treatment.
Abstract 977: Mcl-1 levels critically determines the sensitivities of human colon cancer cells to APG1244, a novel Bcl-2 and Bcl-XLinhibitor, that induces Bax- and caspase-8- dependent apoptosis
Authors: Weilong Yao, Shi-Yong Sun
Journal: Cancer Research (2021)

Abstract Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide due to its poor prognosis. Most of the patients receive surgical resection when diagnosed as CRC, whereas the recurrence rate is very high. Therefore, additional treatment options, such as targeted therapy, are still urgently needed. The novel BH3 mimetic, APG1244 (a prodrug for APG1252), is a highly potent Bcl-2 and Bcl-XL dual inhibitor and being tested in clinical trials as a potential cancer therapeutic agent. The current study focuses on demonstrating the therapeutic efficacies of APG1244 against colorectal cancer and understanding the underlying mechanisms. A panel of CRC cell lines with different levels of Bcl-2, Bcl-XL and Mcl-1 possessed different sensitivities to APG1244. APG1244 effectively decreased the survival of CRC cell lines, particularly those expressing relative low levels of Mcl-1, with induction of apoptosis. High levels of Mcl-1 in these cell lines were significantly correlated to decreased sensitivity to APG1244. APG1244, when combined with a Mcl-1 inhibitor, synergistically decreased the survival and induced apoptosis of APG1244-insensitive cell lines with high levels of Mcl-1. This combination could further decreased the survival and enhanced apoptosis even in the cell lines with relatively low levels of Mcl-1, whereas enforced expression of ectopic Mcl-1 in these cells abrogated APG1244's effects on decreasing cell survival and inducing apoptosis, which can be reversed by Mcl-1 inhibition. In our study, it appears that APG1244 quickly activated caspase-8 and caspase-3 and induced PARP cleavage with induction of cytochrome C and Smac release from mitochondria. Deficiency of Bax, Smac, Bim or PUMA, but not FADD, in CRC cells protected (BAX-KO) or partially protected cells from APG1244-induced apoptosis, indicating that APG1244 induces Bax-dependent apoptosis. Furthermore, blockage of caspase-8 with a caspase-8 specific inhibitor abolished cleavage of caspase-3 and PARP including attenuation of cytochrome C and Smac release induced by APG1244, suggesting a caspase-8-dependent mechanism. The current study thus demonstrates the potential of APG1244 as a monotherapy in the treatment of CRC, particularly those with low Mcl-1 expression, or in combination with a Mcl-1 inhibitor for CRC treatment, warranting further evaluation in vivo and in the clinic. Citation Format: Weilong Yao, Shi-Yong Sun. Mcl-1 levels critically determines the sensitivities of human colon cancer cells to APG1244, a novel Bcl-2 and Bcl-XLinhibitor, that induces Bax- and caspase-8- dependent apoptosis [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 977.
How Somatic Mutations Carve Morphologic Imprint in MDS
Authors: Abhinav Goyal, Mohammad Fahad B Asad, Hassan Awada, Mai Aly, Cassandra M. Hirsch, Bartlomiej P. Przychodzen, Tomas Radivoyevitch, Aziz Nazha, Sudipto Mukherjee, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Yasunobu Nagata
Journal: Blood (2017)