bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-335: Loss of function of the BRCA1-PALB2-BRCA2 axis accelerates p53-associated tumorigenesis
Authors: Huo Yanying , Mahdi Amar , Selenica Pier , Reis-Filho Jorge S S. , Weigelt Britta , Xia Bing 
Published: September 2020

Abstract
The BRCA1-PALB2-BRCA2 axis plays essential roles in the DNA damage response, thereby suppressing genome instability and cancer development. It is widely held that p53 loss promotes BRCA/PALB2-associated tumorigenesis. Here, through parallel conditional knockout of Brca1, Palb2 and Brca2 along with one allele of Trp53 in mice, and by studying mice with a mutation that disengages the PALB2-BRCA1 interaction in different Trp53 backgrounds, we present evidence that support an alternative view, that is, functional loss of the BRCA1-PALB2-BRCA2 axis accelerates p53-associated tumorigenesis. Our results also demonstrate a functional equivalence of BRCA1, PALB2 and BRCA2 in their basic tumor suppressive activity, an epistasis between PALB2 and BRCA2 in tumor suppression, and likely complementary roles of BRCA1 and the PALB2/BRCA2 complex in maintaining cell fitness. These findings may significantly advance the current understanding of the genetic mechanisms that underlie the development of BRCA/PALB2- and p53-associated cancers.
Citation Format: Yanying Huo, Amar Mahdi, Pier Selenica, Jorge S S. Reis-Filho, Britta Weigelt, Bing Xia. Loss of function of the BRCA1-PALB2-BRCA2 axis accelerates p53-associated tumorigenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-335.
Abstract LB-343: A Leu(CAG)-tRNA derived small RNA regulates ribosomal protein S28 after translation initiation in both human and mouse liver cancers
Authors: Kim Hak Kyun , Xu Jianpeng , Chu Kirk , Park Hyesuk , jang Hagoon , Li Pan , Valdmanis Paul , Zhang Qiangpeng , Kay Mark 
Published: September 2020

Abstract
Transfer-RNA-derived small RNA (tsRNA) is implicated in regulating many cellular processes and is dysregulated in various diseases. We recently revealed that the 3′ end of the LeuCAG tRNA-derived small RNA (LeuCAG3′tsRNA) binds to two target sites in human RPS28 mRNA coding region and 3′ UTR, and unwinds their double-stranded secondary structure, which enhances RPS28 translation and subsequently regulates ribosome biogenesis. Inhibition of this tsRNA suppressed the growth of hepatocellular carcinoma in vivo, making it a bona-fide target for cancer therapeutics1. However, the functional conservation between species and the detailed mechanism by which the tsRNA regulates mRNA translation need to be determined in more detailed. Here, we showed that the target site in RPS28 coding region in human is highly conserved in many vertebrate species. While the 3′ UTR target site forms a double-stranded secondary structure with the translation initiation site (TIS) in human RPS28 mRNA, the functional 3′ UTR target site is not present in the species distantly related to human. We revealed that a conserved target site in the mouse Rps28 coding region was sufficient for tsRNA-regulated enhanced translation of the mRNA and cancer cell viability in mouse cell line. Moreover, we demonstrated that the tsRNA regulates mRNA translation after initiation in both human and mouse. Our results have implications for providing additional insights into the biological role of LeuCAG3'tsRNA in post-transcriptional gene regulation and cancer cell viability.1. Kim, HK, et al. (2017). A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature: 1-21doi:10.1038/nature25005.
Citation Format: Hak Kyun Kim, Jianpeng Xu, Kirk Chu, Hyesuk Park, Hagoon jang, Pan Li, Paul Valdmanis, Qiangpeng Zhang, Mark Kay. A Leu(CAG)-tRNA derived small RNA regulates ribosomal protein S28 after translation initiation in both human and mouse liver cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-343.
Abstract LB-356: Deep immune profiling of de novo and recurrent glioblastoma
Authors: Alanio Cécile , Binder Zev A. , O'Rourke Donald M. , Wherry E. John 
Published: September 2020

Abstract
To understand potential immune system alterations in glioblastoma patients and provide a foundation for immunotherapy, we profiled intra tumoral leucocytes from newly diagnosed de novo patients as well as patients with recurrent tumor using high dimensional CyTOF. All recurrent patients underwent standard-of-care therapy, including surgical resection, concurrent temozolomide and radiotherapy, and adjuvant temozolomide. We used two immune profiling panels: a broad profiling panel that includes 45 phenotypic markers that together permit the identification and enumeration of the main innate and adaptive immune cell subsets in humans, and a deep profiling panel that includes 45 features focused on T cell phenotype and biology. We report in both de novo and recurrent tumors a predominant infiltration by CD11b+CD14+ monocytes (43.6±13%. of CD45+ cells). These monocytes displayed an immunomodulatory M2 profile (CD163+HLA-DR-/+CD80-CD86-/+). The adaptive compartment was sparse and dominated by alpha beta T cells, although some mucosal associated invariant T cells and gamma delta T cells were also present. T cells were both conventional T cells and regulatory T cells. The latter tended to be more abundant in the de novo as compared to recurrent tumors (22.8±17.9% of CD4+ T cells in de novo vs 12.9±12.5% in recurrent tumors, P=0.09). Conventional T cells were mostly CD27-CD45RA- effectors, with high expression of PD1 (69.9±17.6% of CD8+ T cells). Using high dimensional approaches, we confirmed that this high expression of PD1 reflects T cell exhaustion, as defined by co-expression of other inhibitory receptors such as Tim3, CTLA-4 and LAG-3. Exhausted T cells typically co-expressed PD1 and CD39 in the de novo tumors, and this pattern was less often observed in recurrent tumors (63.4±22.84% of CD8+ T cells in de novo vs 46.3±14.5% in recurrent tumors, P=0.03). Together, our results highlight the potential issue of a substandard T cell compartment at the time of GBM diagnosis. We are now investigating the mechanisms underlying these observations, as well as their impact on T cell immunity of the patients, as well as current immunotherapy strategies. Our studies should provide a foundation for improving therapy in glioblastoma patients.
Citation Format: Cécile Alanio, Zev A. Binder, Donald M. O'Rourke, E. John Wherry. Deep immune profiling of de novo and recurrent glioblastoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-356.
Abstract LB-399: Late interferon-gamma blockade improves antitumor efficacy of anti-CTLA-4 and anti-PD-1 combination treatment
Authors: Mok Stephen , Chin Renee , Allison James P. 
Published: September 2020

Abstract
The FDA has approved the use of immune checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) for cancer. Patients with metastatic melanoma that receive anti-CTLA-4 have a 22% 10-year overall survival rate, while those treated with anti-PD-1 have a 34% 5-year overall survival rate. The combination treatment of both mediates a 64% overall survival rate. Current literature suggests interferon signaling mediates the expression of inhibitory receptors such as programmed death-ligand 1 (PD-L1) in tumor microenvironment that may affect the responseivness to immunotherapy. However, the role of interferon signaling network throughout the timecourse of treatment remains unclear. In the B16F10 melanoma model, we first show that activated T-cells in combination treated mice produce more interferon-gamma (IFN-gamma) than naïve controls. Then, we have injected mice with anti-IFN-gamma antibody when 1) mice are first treated with combination CTLA-4/PD-1 blockade (early time point) and 2) the combination treatment is finished (late time point). We demonstrated that blocking IFN-gamma at the early time point compromises the antitumor efficacy of the combination treatment. In contrast, the antitumor efficacy of the combination treatment is improved and the expression of inducible co-stimulator (ICOS) on CD8 T-cells is increased if IFN-gamma is blocked at the late time point. Additionally, we found that the expression of PD-L1 in the tumor microenvironment is significantly reduced by IFN-gamma blockade at the late time point. Thus, we treated mice with anti-PD-L1 blocking antibody at the late time point and its antitumor tumor efficacy is similar to the mice treated with anti-IFN-gamma. It suggests that the improved antitumor efficacy of IFN-gamma blockade at the late time point in combination-treated mice is PD-L1 dependent. Collectively, we show that IFN-gamma has a complex and differential role throughout the time course of immunotherapy treatments, and this work suggests a potential combination treatment strategy with checkpoint blockade and late IFN-gamma blockade.
Citation Format: Stephen Mok, Renee Chin, James P. Allison. Late interferon-gamma blockade improves antitumor efficacy of anti-CTLA-4 and anti-PD-1 combination treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-399.
Abstract NG01: MADR: Rapid generation of somatic mosaics to model cancer in mice and human organoids
Authors: Kim Gi Bum , Pacheco David Rincon Fernandez , Saxon David , Yang Amy , Sabat Sara , Dutra-Clarke Marina , Levy Rachelle , Watkins Ashley , Park Hannah , Akhtar Aslam Abbasi , Linesch Paul W. , Kobritz Naomi , Shandra Swasty S. , Grausam Katie , Ayala-Sarmiento Alberto , Molina Jessica , Sedivakova Kristyna , Gareau Daniel S. , Filbin Mariella G. , Bannykh Serguei , Tang Jie , Suva Mario L. , Chen Bin , Danielpour Moise , Breunig Joshua J. 
Published: September 2020

Abstract
In situ transgenesis methods such as virus and electroporation can create somatic transgenic mice quickly, but they lack the exquisite control over copy number, zygosity, and locus specificity. We have recently established mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely-defined chromosomal loci. MADR provides a toolkit of elements for combinatorial labeling, inducible/reversible transgene manipulation, VCre recombinase expression, and genetic manipulation of human cells. Further, we have demonstrated the versatility of MADR by creating glioma models with mixed, reporter-identified zygosity or with “personalized” driver mutations from pediatric glioma. For example, introducing H3f3a mutation variants with MADR regulates the spatiotemporal profile of glioma, and single-cell RNA and ATAC sequencing analysis demonstrates a recapitulation of developmental hierarchy seen in K27M-mutant human glioma. Moreover, we have generated novel models of supratentorial ependymoma using patient-derived oncofusion transgenes. These models display a high degree of fidelity and we now compare these models on a single-cell level with our previous models and human tumor cell transcriptomes. In addition, we now demonstrate the ability to generalize the MADR technology to other non-CNS tissues using local plasmid delivery. Finally, we have engineered human cells to allow for MADR transgenesis and somatic transgenic organoids. These combined approaches will enable researchers to discovery disease mechanisms and test therapeutics in more physiologically relevant cancer models.MADR is extensible to thousands of existing mouse lines and can be adapted to human cells, providing a flexible platform to democratize the generation of somatic transgenic disease models.
Citation Format: Gi Bum Kim, David Rincon Fernandez Pacheco, David Saxon, Amy Yang, Sara Sabat, Marina Dutra-Clarke, Rachelle Levy, Ashley Watkins, Hannah Park, Aslam Abbasi Akhtar, Paul W. Linesch, Naomi Kobritz, Swasty S. Shandra, Katie Grausam, Alberto Ayala-Sarmiento, Jessica Molina, Kristyna Sedivakova, Daniel S. Gareau, Mariella G. Filbin, Serguei Bannykh, Jie Tang, Mario L. Suva, Bin Chen, Moise Danielpour, Joshua J. Breunig. MADR: Rapid generation of somatic mosaics to model cancer in mice and human organoids [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr NG01.
Abstract SY09-03: PROFYLEing Cancer for KiCS: The Canadian Pediatric Precision Oncology Initiative
Authors: Malkin David , Berman Jason N. , Chan Jennifer A. , Denburg Avram , Deyell Rebecca , Eisenstadt David , Fernandez Conrad , Grover Stephanie , Gupta Abha , Hawkings Cynthia , Irwin Meredith , Jabado Nada , Jones Steven , Morgenstern Daniel , Moran Michael , Rasesekh Rod , Shlien Adam , Sinnett Daniel , Sorensen Poul , Sullivan Patrick , Taylor Michael , Villani Anita , Whitlock Jim 
Published: September 2020

Abstract
Each year, approximately 4300 children, adolescents and young adults (CAYA) are diagnosed with cancer. One-third of these patients present with metastatic disease, develop refractory disease or relapse. For these patients, the likelihood of survival remains grim and essentially unchanged in more than three decades. Precision Oncology for Young PeopLE (PROFYLE) is a pan-Canadian, interdisciplinary program that was built on the foundation of three major sequencing efforts in Vancouver (PedsPOG), Toronto (KiCS) and Montreal (TRICEPS) for children with hard-to-treat cancer. Since its inception in 2017, over 700 patients have had complete NGS of paired blood-tumor samples with a goal to not only develop a national precision oncology pipeline, but also to determine the frequency and spectrum of molecular targets for novel therapies and other clinically actionable findings. During this presentation, both the process as well as current findings will be presented and plans for the future will be outlined.
Citation Format: David Malkin, Jason N. Berman, Jennifer A. Chan, Avram Denburg, Rebecca Deyell, David Eisenstadt, Conrad Fernandez, Stephanie Grover, Abha Gupta, Cynthia Hawkings, Meredith Irwin, Nada Jabado, Steven Jones, Daniel Morgenstern, Michael Moran, Rod Rasesekh, Adam Shlien, Daniel Sinnett, Poul Sorensen, Patrick Sullivan, Michael Taylor, Anita Villani, Jim Whitlock. PROFYLEing Cancer for KiCS: The Canadian Pediatric Precision Oncology Initiative [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr SY09-03.
Experimental simplified rule of self tuning fuzzy logic-model reference adaptive speed controller for induction motor drive
Authors: Ismail M.Z. , Talib M.H.N. , Ibrahim Z. , Mat Lazi J. , Rasin Z. 
Published: September 2020

<span>Fuzzy logic controller (FLC) has shown excellent performance in dealing with the non-linearity and complex dynamic model of the induction motor. However, a conventional constant parameter FLC (CPFL) will not be able to provide–good coverage performance for a wide speed range operation with a single tuning parameter. Therefore, this paper proposed a self tuning mechanism FLC approach by model reference adaptive controller (ST-MRAC) to continuously allow to adjust the parameters. Due to real time hardware application, the dominant rules selection method for simplified rules has been implemented as part of the reducing computational burden. Experiment results validate a good performance of the ST-MRAC compared to the CPFL for the speed performance in terms of the wide range of operations and disturbance showed remarkable performance.</span>
Effects of ON-Hours Versus OFF-Hours Admission on Outcome in Patients With Myocardial Infarction and Cardiogenic Shock
Authors: Sag Can Martin , Zeymer Uwe , Ouarrak Taoufik , Schneider Steffen , Montalescot Gilles , Huber Kurt , Fuernau Georg , Freund Anne , Feistritzer Hans-Josef , Desch Steffen , Thiele Holger , Maier Lars S. 
Published: September 2020

Background:
The management of patients with acute myocardial infarction complicated by cardiogenic shock is highly complex, and outcomes may depend on the time of hospital admission and subsequent intervention (ie, ON-hours versus OFF-hours). The CULPRIT-SHOCK trial (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) demonstrated superior outcome for culprit-lesion-only versus immediate multivessel percutaneous coronary intervention in patients presenting with acute myocardial infarction, multivessel disease, and cardiogenic shock. However, it is unknown whether the time of hospital admission affects the overall outcome of these high-risk patients.

Methods:
We analyzed patients from the CULPRIT-SHOCK trial with respect to the time of hospital admission. We divided patients in ON-hours and OFF-hours groups and further stratified them according to their individual revascularization strategy. Outcome measures consisted of a composite end point of death or renal-replacement therapy within 30 days and mortality within 1 year.

Results:

Out of 686 patients randomized in the CULPRIT-SHOCK trial, 444 patients (64.7%) presented during ON-hours, whereas 242 patients (35.3%) presented during OFF-hours. Death or renal-replacement therapy at 30 days occurred to a similar extent in patients admitted during ON-hours (51.0%) and OFF-hours (50.0%;
P
=0.80). Similarly, 1-year mortality was not affected by the time of hospital admission (54.4% ON-hours versus 51.7% OFF-hours,
P
=0.49). Regardless of admission time, patients had a benefit from culprit-lesion-only as compared to immediate multivessel percutaneous coronary intervention. The composite end point at 30 days occurred in 45.1% versus 57.6% of patients admitted ON-hours and in 47.7% versus 51.9% of patients admitted OFF-hours (
P
interaction
=0.29). Death within 1 year occurred in 49.4% versus 60.0% of patients admitted during ON-hours and in 51.4% versus 51.9% of patients admitted OFF-hours (
P
interaction
=0.20).

Conclusions:
Among patients with myocardial infarction and cardiogenic shock, the risk of death or renal-replacement therapy at 30 days, and mortality at 1 year did not differ significantly according to the time of hospital admission.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01927549.
Variable CD34+ recovery of cryopreserved allogeneic HPC products: transplant implications during the COVID-19 pandemic
Authors: Purtill Duncan , Antonenas Vicki , Chiappini Paul , Tong Daochen , O’Flaherty Elizabeth , Bajel Ashish , Kabani Karieshma , Larsen Stephen , Tan Suikeat , Hutchins Cheryl , Curtis David J. , Kennedy Glen A. , Watson Anne-Marie , Bai LiJun , Greenwood Matthew , Gottlieb David J. , Hamad Nada 
Published: September 2020

Abstract
Donor registries and transplantation societies recommend cryopreservation of unrelated donor hemopoietic progenitor cell (HPC) products before the recipient commences conditioning therapy to mitigate the donor and travel risks associated with the COVID-19 pandemic. However, little is known regarding the postthaw quality of such allogeneic products or the effect of precryopreservation storage and processing on these characteristics. We investigated the postthaw CD34+ cell recovery and viability of 305 allogeneic HPC products cryopreserved at 9 laboratories across Australia. Median postthaw CD34+ cell recovery was 76% and ranged from 6% to 122%. Longer transit time before cryopreservation, white cell count (WCC) during storage, and complex product manipulation before cryopreservation were independently associated with inferior postthaw CD34+ cell recovery. Longer precryopreservation transit time and WCC were also associated with inferior postthaw CD34+ cell viability. We conclude that although postthaw CD34+ cell recovery and viability of cryopreserved allogeneic HPC is generally acceptable, there is a significant risk of poor postthaw product quality, associated with prolonged storage time, higher WCC, and complex product manipulation precryopreservation. Awareness of expected postthaw recovery and practices that influence it will assist collection, processing, and transplant centers in optimizing outcomes for transplant recipients.
Thermal Decomposition In Situ Monitoring System of the Gas Phase Cyclopentadienyl Tris(dimethylamino) Zirconium (CpZr(NMe2)3) Based on FT-IR and QMS for Atomic Layer Deposition
Authors: An Jong-Ki , Choi Eunmi , Shim Seob , Kim Hayeong , Kang Goru , Yun Ju-Young 
Published: September 2020

AbstractWe developed a newly designed system based on in situ monitoring with Fourier transform infrared (FT-IR) spectroscopy and quadrupole mass spectrometry (QMS) for understanding decomposition mechanism and by-products of vaporized Cyclopentadienyl Tris(dimethylamino) Zirconium (CpZr(NMe2)3) during the move to process chamber at various temperatures because thermal decomposition products of unwanted precursors can affect process reliability. The FT-IR data show that the –CH3 peak intensity decreases while the –CH2– and C=N peak intensities increase as the temperature is increased from 100 to 250 °C. This result is attributed to decomposition of the dimethylamido ligands. Based on the FT-IR data, it can also be assumed that a new decomposition product is formation at 250 °C. While in situ QMS analysis demonstrates that vaporized CpZr(NMe2)3 decomposes to N-ethylmethanimine rather than methylmethyleneimine. The in situ monitoring with FT-IR spectroscopy and QMS provides useful information for understanding the behavior and decomposes of CpZr(NMe2)3 in the gas phase, which was not proven before. The study to understand the decomposition of vaporized precursor is the first attempt and can be provided as useful information for improving the reliability of a high- advanced ultra-thin film deposition process using atomic layer deposition in the future.
ZnO UV Photodetectors Modified by Ag Nanoparticles Using All-Inkjet-Printing
Authors: Wang Hsiang-Chun , Hong Yuehua , Chen Zhangwei , Lao Changshi , Lu Youming , Yang Zhichao , Zhu Youhua , Liu Xinke 
Published: September 2020

AbstractTo further improve the performance of all-inkjet-printing ZnO UV photodetector and maintain the advantages of inkjet printing technology, the inkjet printing Ag nanoparticles (NPs) were deposited on the inkjet printing ZnO UV photodetector for the first time. The inkjet printing Ag NPs can passivate the surface defects of ZnO and work as surface plasmons from the characterization of photoluminescence (PL), X-ray photoelectron spectroscopy (XPS), and finite difference time domain method (FDTD) simulation. The normalized detectivity (D*) of the Ag NP-modified detector reaches to 1.45 × 1010Jones at 0.715 mW incident light power, which is higher than that of 5.72 × 109Jones of the bare ZnO photodetector. The power-law relationship between the photocurrent and the incident light power of the Ag NP-modified ZnO detector isIpc ∝ P2.34, which means the photocurrent is highly sensitive to the change of incident light power.