tbuckley/cabot-search huggingface dataset:
Abstract 2785: Efficacy evaluation of candidate therapeutics in immuno-oncology by in vitro suppressive bioassays using macrophages
Authors: Thibaut J. Janss, Joahn Arnold, Juliette Lamy, Ellen Boelen
Journal: Cancer Research (2021)

Abstract The increasing interest in the tumor microenvironment leads to a focus on new bioassays to represent all the players of the cancer immune response. Some of these players like Tumor Associated Macrophages (TAMs) often exhibit an immunosuppressive phenotype by downregulating the anti-tumor response. Their regulation mechanisms constitute an important target for new therapeutics. In order to study these mechanisms in a human model, suppressive bioassays mimicking the suppressive action of these cells on T cell activation, were developed. An important player in the tumor microenvironment are macrophages which possess important active and regulatory functions in both innate and adaptive immune responses. Classical activated macrophages, classified as M1-like macrophages, comprise immune effector cells with an acute inflammatory phenotype while the alternatively activated M2-like macrophages have suppressive and healing capacities. TAMs are present at high densities in solid tumors and share many characteristics with M2-like macrophages. In vitro assays using M1- and M2-like macrophages can be a first step to screen the effect of the test molecules on the phenotype and function of macrophages. For example, macrophage precursors display extraordinary plasticity in response to exogenous and endogenous stimuli which can result in a M2- or M1-like status. Using in vitro polarization and functional assays, the potential effect of molecules on M1- and M2-like macrophage generation and polarization can be screened. Next to that, the test molecules' impact on the functionality of macrophages can be evaluated in a suppressive assay. Here, the ability of the molecules to reverse the stimulating versus suppressive effect of the M1- and M2-like macrophages on T cells can be determined by measuring proliferation and cytokine production. The use of bioassays contributes to a better understanding of the tumor microenvironment. The steps needed to generate an anti-tumor response by the immune system will help to assess the functional potential of new drugs, design clinical trials and ultimately discover relevant biomarkers Citation Format: Thibaut J. Janss, Joahn Arnold, Juliette Lamy, Ellen Boelen. Efficacy evaluation of candidate therapeutics in immuno-oncology by in vitro suppressive bioassays using macrophages [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 2785.
Kidney transplantation from Donation after Cardiocirculatory Death (DCD) after Extracorporeal Membrane Oxygenation (ECMO) – What can we say after 5 years of experience?
Authors: M. Manso, T. Pina-Vaz, L. Pacheco-Figueiredo, T. Antunes-Lopes, G. Oliveira, F. Cruz, P. Dinis-Oliveira, J. Silva
Journal: European Urology (2021)
Long-term outcomes of Penile Squamous Cell Carcinoma (SCC) patients with sarcomatoid variant compared to non-sarcomatoid group - An eUROGEN study
Authors: H.M. Alnajjar, M. Rewhorn, F. Castiglione, A. Cayetano Alcaraz, N. Schifano, C. Akers, A. Haider, A. Freeman, P. Hadway, R. Nigam, R. Rees, A. Mitra, C. Alifrangis, A. Muneer
Journal: European Urology (2021)
Large ureterolithiasis: Ureteroscopic lithotripsy or robotic ureterolithotomy?
Authors: W-S. Hu, Y-S. Lin, W-C. Weng, L-H. Huang, Z-M. Huang, S-S. Tse, C-Y. Hsu, M-C. Tung, Y-C. Ou
Journal: European Urology (2021)
Acceptability of Adolescent COVID-19 Vaccination Among Adolescents and Parents of Adolescents — United States, April 15–23, 2021
Authors: Aaron M. Scherer, Amber M. Gedlinske, Andrew M. Parker, Courtney A. Gidengil, Natoshia M. Askelson, Christine A. Petersen, Kate R. Woodworth, Megan C. Lindley
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

On May 10, 2021, the Food and Drug Administration (FDA) expanded its Emergency Use Authorization for the Pfizer-BioNTech COVID-19 vaccine to include adolescents aged 12-15 years; this authorization was followed by interim recommendations from the Advisory Committee on Immunization Practices (ACIP) for the vaccine among this age group (1). Using data from nonprobability-based Internet panel surveys administered by the Healthcare and Public Perceptions of Immunizations (HaPPI) Survey Collaborative, the acceptability of adolescent COVID-19 vaccination and self-reported factors increasing vaccination intent were assessed among independently recruited samples of 985 adolescents aged 13-17 years and 1,022 parents and guardians (parents) of adolescents aged 12-17 years during April 15-April 23, 2021, prior to vaccine authorization for this age group. Approximately one quarter (27.6%) of parents whose adolescents were already vaccine-eligible (i.e., aged 16-17 years) reported their adolescent had received ≥1 COVID-19 vaccine dose, similar to the proportion reported by vaccine-eligible adolescents aged 16-17 years (26.1%). However, vaccine receipt reported by parents of adolescents differed across demographic groups; parents identifying as female or Hispanic, or who had an education lower than a bachelor's degree reported the lowest adolescent COVID-19 vaccination receipt. Among parents of unvaccinated adolescents aged 12-17 years, 55.5% reported they would "definitely" or "probably" have their adolescent receive a COVID-19 vaccination. Among unvaccinated adolescents aged 13-17 years, 51.7% reported they would "definitely" or "probably" receive a COVID-19 vaccination. Obtaining more information about adolescent COVID-19 vaccine safety and efficacy, as well as school COVID-19 vaccination requirements, were the most commonly reported factors that would increase vaccination intentions among both parents and adolescents. Federal, state, and local health officials and primary care professionals were the most trusted sources of COVID-19 vaccine information among both groups. Efforts focusing on clearly communicating to the public the benefits and safety of COVID-19 vaccination for adolescents, particularly by health care professionals, could help increase confidence in adolescent COVID-19 vaccine and vaccination coverage.
Psychological distress, resettlement stress, and lower school engagement among Arabic-speaking refugee parents in Sydney, Australia: A cross-sectional cohort study
Authors: Jess R. Baker, Derrick Silove, Deserae Horswood, Afaf Al-Shammari, Mohammed Mohsin, Susan Rees, Valsamma Eapen
Journal: PLoS Medicine (2021)

Schools play a key role in supporting the well-being and resettlement of refugee children, and parental engagement with the school may be a critical factor in the process. Many resettlement countries have policies in place to support refugee parents' engagement with their children's school. However, the impact of these programs lacks systematic evaluation. This study first aimed to validate self-report measures of parental school engagement developed specifically for the refugee context, and second, to identify parent characteristics associated with school engagement, so as to help tailor support to families most in need.The report utilises 2016 baseline data of a cohort study of 233 Arabic-speaking parents (77% response rate) of 10- to 12-year-old schoolchildren from refugee backgrounds across 5 schools in Sydney, Australia. Most participants were born in Iraq (81%) or Syria (11%), and only 25% spoke English well to very well. Participants' mean age was 40 years old, and 83% were female. Confirmatory factor analyses were run on provisional item sets identified from a literature review and separate qualitative study. The findings informed the development of 4 self-report tools assessing parent engagement with the school and school community, school belonging, and quality of the relationship with the schools' bilingual cultural broker. Cronbach alpha and Pearson correlations with an established Teacher-Home Communication subscale demonstrated adequate reliability (α = 0.67 to 0.80) and construct and convergent validity of the measures (p < 0.01), respectively. Parent characteristics were entered into respective least absolute shrinkage and selection operator (LASSO) regression analyses. The degree of parents' psychological distress (as measured by the Kessler10 self-report instrument) and postmigration living difficulties (PLMDs) were each associated with lower school engagement and belonging, whereas less time lived in Australia, lower education levels, and an unemployed status were associated with higher ratings in relationship quality with the schools' cultural broker. Study limitations include the cross-sectional design and the modest amount of variance (8% to 22%) accounted for by the regression models.The study offers preliminary refugee-specific measures of parental school engagement. It is expected they will provide a resource for evaluating efforts to support the integration of refugee families into schools. The findings support the need for initiatives that identify and support parents with school-attending children from refugee backgrounds who are experiencing psychological distress or resettlement stressors. At the school level, the findings suggest that cultural brokers may be effective in targeting newly arrived families.
Inter-kingdom relationships in Crohn’s disease explored using a multi-omics approach
Authors: Alessandra Frau, Umer Z. Ijaz, Rachael Slater, Daisy Jonkers, John Penders, Barry J. Campbell, John G. Kenny, Neil Hall, Luca Lenzi, Michael D. Burkitt, Marieke Pierik, Alistair C. Darby, Christopher S. J. Probert
Journal: Gut Microbes (2021)

The etiology of Crohn's disease (CD) is multifactorial. Bacterial and fungal microbiota are involved in the onset and/or progression of the disease. A bacterial dysbiosis in CD patients is accepted; however, less is known about the mycobiome and the relationships between the two communities. We investigated the interkingdom relationships, their metabolic consequences, and the changes in the fungal community during relapse and remission in CD.Two cohorts were evaluated: a British cohort (n = 63) comprising CD and ulcerative colitis patients, and controls. The fungal and bacterial communities of biopsy and fecal samples were analyzed, with the fecal volatiles; datasets were also integrated; and a Dutch cohort (n = 41) comprising CD patients and healthy controls was analyzed for stability of the gut mycobiome.A dysbiosis of the bacterial community was observed in biopsies and stool. Results suggest Bacteroides is likely key in CD and may modulate Candida colonization. A dysbiosis of the fungal community was observed only in the Dutch cohort; Malassezia and Candida were increased in patients taking immunosuppressants. Longitudinal analysis showed an increase in Cyberlindnera in relapse. Saccharomyces was dominant in all fecal samples, but not in biopsies, some of which did not yield fungal reads; amino acid degradation was the main metabolic change associated with CD and both bacteria and fungi might be implicated.We have shown that Bacteroides and yeasts may play a role in CD; understanding their role and relationship in the disease would shed new light on the development and treatment of CD.
Local Adaptation of Bitter Taste and Ecological Speciation in a Wild Mammal
Authors: Hengwu Jiao, Qian Wang, Bing-Jun Wang, Kexin Li, Matěj Lövy, Eviatar Nevo, Qiyang Li, Wenchuan Su, Peihua Jiang, Huabin Zhao
Journal: Molecular Biology and Evolution (2021)

Abstract Sensory systems are attractive evolutionary models to address how organisms adapt to local environments that can cause ecological speciation. However, tests of these evolutionary models have focused on visual, auditory, and olfactory senses. Here, we show local adaptation of bitter taste receptor genes in two neighboring populations of a wild mammal—the blind mole rat Spalax galili—that show ecological speciation in divergent soil environments. We found that basalt-type bitter receptors showed higher response intensity and sensitivity compared with chalk-type ones using both genetic and cell-based functional analyses. Such functional changes could help animals adapted to basalt soil select plants with less bitterness from diverse local foods, whereas a weaker reception to bitter taste may allow consumption of a greater range of plants for animals inhabiting chalk soil with a scarcity of food supply. Our study shows divergent selection on food resources through local adaptation of bitter receptors, and suggests that taste plays an important yet underappreciated role in speciation.
Efficacy and safety of surgical treatments for neurogenic stress urinary incontinence in adults: A systematic review
Authors: S. Musco, H. Ecclestone, L. ‘t Hoen, B.F.M. Blok, B. Padilla-Fernández, G. Del Popolo, J. Groen, J. Pannek, T.M. Kessler, G. Karsenty, V. Phé, A.M. Sartori, D. Castro-Diaz, R. Hamid
Journal: European Urology (2021)
Benefits and harms of Botulinum Toxin-A in the treatment of chronic pelvic pain syndromes: Systematic review by the EAU Chronic Pelvic Pain Panel
Authors: B. Parsons, S. Goonewardene, S. Dabestani, L. Pacheco-Figueiredo, Y. Yuan, V. Zumstein, A. Cottrell, J. Borovicka, P. Dinis-Oliveira, B. Berghmans, S. Elneil, J. Hughes, B.E.J. Messelink, A.C. De C Williams, A.P. Baranowski, D.S. Engeler
Journal: European Urology (2021)
DNA Damage Repair (DDR) gene and VHL concurrent alterations in advanced clear cell Renal Cell Carcinoma (ccRCC) are association with good progression free survival with tyrosine kinase inhibitor therapy
Authors: W. Zhai, J. Wang, N. He, J. Zhou, J. Wang, Y. Xue, Z. Yang, Y.. Chen, J. Hui, J. Haung, W. Kong, Y. Haung, W. Xue
Journal: European Urology (2021)
Abstract P082: The Association Between Traditional Cardiovascular Disease Risk Factors and Small Vessel Lower Extremity Arterial Disease In a Healthy Community-dwelling Population: Rancho Bernardo Study
Authors: Jan M Hughes-Austin, Michael H Criqui, Elizabeth Barrett-Connor
Journal: Circulation (2013)

Background:  A prior report suggested that small vessel lower extremity arterial disease (svLEAD) was pathophysiologically and epidemiologically distinct from large vessel LEAD (lvLEAD). In a healthy community-dwelling older Caucasian population, we investigated whether traditional CVD risk factors independently contributed to svLEAD, as they did to lvLEAD, and whether the combination of these factors was more strongly associated with disease prevalence.   Methods:  We evaluated 965 Rancho Bernardo Study participants with complete measures of ankle-brachial index (ABI), toe-brachial index (TBI), and traditional CVD risk factors. SvLEAD was defined by bilateral normal ABI (1.0-1.4) with bilateral TBI    Results:  Eighty participants (8.3%) met svLEAD criteria. Table 1 presents odds ratios (ORs) for associations of svLEAD with traditional CVD risk factors, MS, and GFRS within the study population as well as stratified by sex. While considering all potential CVD risk factors in our full analysis, only relevant predictors are included in Table 1. Age, male sex, LDL-C and pack-years of smoking were positively associated with svLEAD; and heart rate and waist circumference were inversely associated with svLEAD. These associations did not differ by sex.   Conclusion:  Associations between svLEAD and pack-years of smoking, male sex, and LDL-C suggest that svLEAD shares similar risk factors with lvLEAD. Lack of svLEAD associations with other CVD risk factors and their combinations as Metabolic Syndrome or General Framingham Risk Score, however, continues to suggest different pathophysiology.
Abstract 2959: Establishment of KRAS-G12C inhibitor induced resistant tumor models enable the development of new generation KRAS-G12C inhibitors and combinatorial strategies
Authors: Gaoxiang Liu, Wenting Shi, Qingyang Gu, Qunsheng Ji
Journal: Cancer Research (2021)

Abstract The KRAS (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) gene is one of the most popular oncogenes in the recent targeted therapy research. Activating KRAS mutations including G12C, G12D, etc are detected in around 25% of human cancers. The most common KRAS mutation is G12C, which comprises nearly 15% of lung adenocarcinoma, 8% of colorectal carcinoma and 4% of pancreatic adenocarcinoma. AMG-510 from Amgen and MRTX849 from Mirati Therapeutics both targeting KRASG12C mutant have shown encouraging activities in early clinical trials, especially shown a better overall response rate (ORR) and disease control rate (DCR) in KRASG12C mutant non-small cell lung cancer (NSCLC). However, acquired resistance to KRAS-G12C inhibitors will occur after prolonged treatment, which limits the effective evaluation in clinical trials. Various combinatorial strategies have been tried to overcome the resistance to KRAS-G12C inhibitors, including co-targeting vertical Ras signaling pathway and combining KRAS-G12C inhibitors with chemotherapeutics or immunotherapies. In order to facilitate the development of KRAS-G12C inhibitors, we have established an AMG510 resistant MIA PaCa-2 pancreatic adenocarcinoma CDX model and several colorectal carcinoma PDX models. These resistant models were derived from sensitive models carrying KRASG12C mutation, by prolonged treatment of AMG510 during several passages until a stable drug resistance phenotype occurred. To explore the resistant mechanisms, we performed Western blotting on downstream effectors ERK and found AMG510 produced less inhibition effect on ERK phosphorylation level in the resistant models. We are also developing more CDX and PDX models which are resistant to KRAS-G12C inhibitors. Therefore these models can be used to simulate acquired resistance to KRAS-G12C inhibitors after prolonged treatment in clinic, and provide a new tool to evaluate new generation of KRAS-G12C inhibitors as well as the combinatorial strategies with KRAS-G12C inhibitors. Citation Format: Gaoxiang Liu, Wenting Shi, Qingyang Gu, Qunsheng Ji. Establishment of KRAS-G12C inhibitor induced resistant tumor models enable the development of new generation KRAS-G12C inhibitors and combinatorial strategies [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 2959.
Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time
Authors: Daniel K. Lee, S. William Li, Firas Bounni, Gabriel Friedman, Mohsen Jamali, Leah Strahs, Omer Zeliger, Pauline Gabrieli, Michael A. Stankovich, Jack Demaree, Ziv M. Williams
Journal: Nature Neuroscience (2021)
リポ蛋白質(a)は急性心筋梗塞患者の責任病変でのプラーク形態を決定する重要因子である
Authors: Hikita Hiroyuki, Satoh Akira, Kawashima Tomoyuki, Miyazaki Toru, Tamura Mieko, Ohhigashi Hirokazu, Miyazaki Shinsuke, Takahashi Yoshihide, Kobori Atsushi, Nozato Toshihiro, Takei Asumi, Kuwahara Taishi, Hiroe Michiaki, Isobe Mitsuaki, Takahashi Atsushi
Journal: Circulation (2008)
Standardized uptake values as determined on PSMA PET/CT are associated with higher Gleason grade and lower biochemical-free recurrence rates in patients with prostate cancer
Authors: Y.J.L. Bodar, H. Veerman, K. De Bie, D. Meijer, P.J. Van Leeuwen, M.L. Donswijk, N.H. Hendrikse, R. Boellaard, D.E. Oprea-Lager, A.N. Vis
Journal: European Urology (2021)
Abstract 1560: Targeting RNA-binding protein HuR to improve anti-PD-1 immunotherapy response in breast cancer
Authors: Qi Zhang, Xiaoqing Wu, Lan Lan, Lanjing Wei, Liang Xu
Journal: Cancer Research (2021)

Abstract Breast cancer has been considered as a less immune-sensitive disease. Patients with metastatic breast cancer have a particularly low objective response rate (ORR) to anti-PD-1/PD-L1 therapy (3%~24%). It will be valuable to improve the treatment efficacy of anti-PD-1 immunotherapy in breast cancer. Recent studies reported that exosomal PD-L1 derived from tumor cells mediated immune surveillance evasion by interacting with the PD-1 receptor on T cells and contributed to the low ORR in anti-PD-1/PD-L1 immunotherapy.The RNA-binding protein Hu antigen R (HuR) is a member of the embryonic lethal abnormal vision (ELAV) family that is overexpressed in a variety of cancers and promotes tumorigenesis by interacting with a subset of oncogenic mRNAs, including PD-L1 mRNA. HuR also plays an important role in the exosome secretion process by regulating RAB27B mRNA. In this study, we aim to identify HuR biological functions in the cancer-immune system and evaluate the combination strategy using a HuR inhibitor with an anti-PD-1 antibody in breast cancer. We show here the direct binding of HuR protein to PD-L1 mRNA in human breast cancer cell line MDA-MB-231 by Ribonucleoprotein immunoprecipitation (RNP-IP). We also show that PD-L1 protein expression level is decreased in HuR knockout clones and in exosomes derived from HuR knockout clones. HuR knockout downregulates exosome secretion with decreased size in MDA-MB-231 cells. KH-3 is a small molecule identified from several chemical libraries that disrupts the binding of HuR and its target mRNAs.To test the combination strategy using a HuR inhibitor and anti-PD-1 antibody in vivo, we established the EMT6 orthotopic mouse breast cancer model. A combination treatment with HuR inhibitor KH-3 and anti-PD-1 antibody inhibits tumor growth and prolongs survival in this breast cancer model. In conclusion, we preliminarily explored the role of HuR in the cancer-immune system, we showed that HuR may be a promising therapeutic target to overcome immune evasion and improve immunotherapy response in breast cancer. Citation Format: Qi Zhang, Xiaoqing Wu, Lan Lan, Lanjing Wei, Liang Xu. Targeting RNA-binding protein HuR to improve anti-PD-1 immunotherapy response in breast 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 1560.
Characterization of systemic immunosuppression by IDH mutant glioma small extracellular vesicles
Authors: Nils Ludwig, Aparna Rao, Poorva Sandlesh, Saigopalakrishna S Yerneni, Alexander D Swain, Kristin M Bullock, Kim M Hansen, Xiaoran Zhang, Emade Jaman, Jordan Allen, Katharine Krueger, Chang-Sook Hong, William A Banks, Theresa L Whiteside, Nduka M Amankulor
Journal: Neuro-Oncology (2021)

Abstract Background Gliomas are the most common primary brain tumors and are universally fatal. Mutations in the isocitrate dehydrogenase genes (IDH1 and IDH2) define a distinct glioma subtype associated with an immunosuppressive tumor microenvironment. Mechanisms underlying systemic immunosuppression in IDH mutant (mutIDH) gliomas are largely unknown. Here, we define genotype-specific local and systemic tumor immunomodulatory functions of tumor-derived glioma small extracellular vesicles (TEX). Methods TEX produced by human and murine wildtype and mutant IDH glioma cells (wtIDH and mutIDH, respectively) were isolated by size exclusion chromatography (SEC). TEX morphology, size, quantity, molecular profiles and biodistribution were characterized. TEX were injected into naive and tumor-bearing mice, and the local and systemic immune microenvironment composition was characterized. Results Using in vitro and in vivo glioma models, we show that mutIDH TEX are more numerous, possess distinct morphological features and are more immunosuppressive than wtIDH TEX. mutIDH TEX cargo mimics their parental cells, and induces systemic immune suppression in naive and tumor-bearing mice. TEX derived from mutIDH gliomas and injected into wtIDH tumor-bearing mice reduce tumor-infiltrating effector lymphocytes, dendritic cells and macrophages, and increase circulating monocytes. Astonishingly, mutIDH TEX injected into brain tumor-bearing syngeneic mice accelerate tumor growth and increase mortality compared with wtIDH TEX. Conclusions Targeting of mutIDH TEX represents a novel therapeutic approach in gliomas.