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At least 289 records · Page 16
All sourcesNASA NTRSDOE OSTI
DOE OSTI2021

Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial

The survival results of the PORTEC-3 trial showed a significant improvement in both overall and failure-free survival with chemoradiation therapy versus pelvic radiation therapy alone. The present analysis was performed to compare long-term adverse events (AE) and health-related quality of life (HRQOL).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Executive Summary of the American Radium Society Appropriate Use Criteria for Radiation Treatment of Node-Negative Muscle Invasive Bladder Cancer

Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Overcoming Barriers to Radiopharmaceutical Therapy (RPT): An Overview From the NRG-NCI Working Group on Dosimetry of Radiopharmaceutical Therapy

Radiopharmaceutical therapy (RPT) continues to demonstrate tremendous potential in improving the therapeutic gains in radiation therapy by specifically delivering radiation to tumors that can be well assessed in terms of dosimetry and imaging. Dosimetry in external beam radiation therapy is standard practice. This is not the case, however, in RPT. This NRG (acronym formed from the first letter of the 3 original groups: National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group)-National Cancer Institute Working Group review describes some of the challenges to improving RPT. The main priorities for advancing the field include (1) developing and adopting best practice guidelines for incorporating patient-specific dosimetry for RPT that can be used at both large clinics with substantial resources and more modest clinics that have limited resources, (2) establishing and improving strategies for introducing new radiopharmaceuticals for clinical investigation, (3) developing approaches to address the radiophobia that is associated with the administration of radioactivity for cancer therapy, and (4) solving the financial and logistical issues of expertise and training in the developing field of RPT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

N6-methyladenine demethylase ALKBH1 inhibits the differentiation of skeletal muscle

Highlights: • The DNA N6-mA modification increased during skeletal muscle development, accompanied by a strong decrease of ALKBH1. • ALKBH1 enhanced proliferation and inhibited differentiation of C2C12 cells. • ALKBH1 impaired multiple genes and signaling pathways to promote proliferation and inhibit differentiation of C2C12 cells. DNA N{sup 6}-methyladenine (N6-mA) was recently recognized as a new epigenetic modification in mammalian genome, and ALKBH1 was discovered as its demethylase. Knock-out mice studies revealed that ALKBH1 was indispensable for normal embryonic development. However, the function of ALKBH1 in myogenesis is largely unknown. In this study, we found that N6-mA showed a steady increase, going along with a strong decrease of ALKBH1 during skeletal muscle development. Our results also showed that ALKBH1 enhanced proliferation and inhibited differentiation of C2C12 cells. Genome-wide transcriptome analysis and reporter assays further revealed that ALKBH1 accomplished the differentiation inhibiting function by regulating a core set of genes and multiple signaling pathways, including increasing chemokine (C-X-C motif) ligand 14 (CXCL14) and activating ERK signaling. Taken together, our results demonstrated that ALKBH1 is critical for the myogenic differentiation of C2C12 cells, and suggested that N6-mA might be a new epigenetic mechanism for the regulation of myogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

PCGF3 promotes the proliferation and migration of non-small cell lung cancer cells via the PI3K/AKT signaling pathway

Highlights: • PCGF3 is highly expressed in non-small cell lung cancer (NSCLC) tissues. • PCGF3 overexpression positively correlates with lymph node metastasis and p-TNM staging. • PCGF3 promotes NSCLC cells proliferation by regulating CyclinB1, CyclinD1, and CDK4. • PCGF3 promotes NSCLC cells migration by regulating RhoA, RhoC, and CDC42. • PCGF3 promotes malignant behavior in NSCLC by positively regulating the PI3K/AKT signaling pathway. The Polycomb Group Ring Finger 3 (PCGF3) protein has been reported to be significantly upregulated in pancreatic islet tumors and related to signal transduction; however, its detailed mechanisms and biological roles in other tumors, including non-small cell lung cancer (NSCLC), remain unclear. This study investigated the function of PCGF3 in NSCLC and further elucidated its mechanism of action. The immunohistochemical analysis of 86 selected lung cancer tissues revealed that PCGF3 was highly expressed in NSCLC tissues and positively correlated with lymph node metastasis and p-TNM staging. Additionally, PCGF3 promoted cell proliferation in lung cancer by regulating CyclinB1, CyclinD1, and CDK4 expression, and also promoting their migration by regulating RhoA, RhoC, and CDC42. Furthermore, PCGF3 affected both the proliferation and migration of lung cancer cells by regulating the PI3K/AKT pathway, as verified by inhibiting this pathway using LY294002. The findings of this study suggested that PCGF3 is associated with poor prognosis in patients with NSCLC and could therefore be an important biomarker for treating and preventing NSCLC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

MiR-375 silencing attenuates pro-inflammatory macrophage response and foam cell formation by targeting KLF4

Macrophage mediated inflammation and foam cell formation play crucial roles in the development of atherosclerosis. MiR-375 is a small noncoding RNA that significantly implicated in multiple tumor regulation and has been emerged as a novel biomarker for type 2 diabetes. However, the exact role of miR-375 on macrophage activation remains unknown. In the present study, we observed that miR-375 expression showed an up-regulated expression in atherosclerotic aortas, as well as in bone marrow derived macrophages (BMDMs) and mouse peritoneal macrophages (MPMs) isolated from ApoE deficiency mice and was gradually increased followed the Ox-LDL treated time. Functionally, miR-375 inhibition significantly decreased foam cell formation accompanied by up-regulated genes expression involved in cholesterol efflux but reduced genes expression implicated in cholesterol influx. Moreover, miR-375 silencing increased resolving M2 macrophage but reduced pro-inflammatory M1 macrophage markers expression. Such above effects can be reversed by miR-375 overexpression. Mechanistically, we noticed that miR-375 knockdown promoted KLF4 expression which was required for the ameliorated effect of miR-375 silencing on macrophage activation. Importantly, the consistent results in mRNA expression of M1 and M2 markers were observed in vivo, and miR-375{sup −/−}ApoE{sup −/−} mice significant decreased atherosclerotic lesions in the whole aorta and aortic sinus. Taken together, these evidences suggested that miR-375 knockdown attenuated macrophage activation partially through activation of KLF4-dependent mechanism.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Alert Classification for the ALeRCE Broker System: The Light Curve Classifier

We present the first version of the Automatic Learning for the Rapid Classification of Events (ALeRCE) broker light curve classifier. ALeRCE is currently processing the Zwicky Transient Facility (ZTF) alert stream, in preparation for the Vera C. Rubin Observatory. The ALeRCE light curve classifier uses variability features computed from the ZTF alert stream and colors obtained from AllWISE and ZTF photometry. We apply a balanced random forest algorithm with a two-level scheme where the top level classifies each source as periodic, stochastic, or transient, and the bottom level further resolves each of these hierarchical classes among 15 total classes. This classifier corresponds to the first attempt to classify multiple classes of stochastic variables (including core- and host-dominated active galactic nuclei, blazars, young stellar objects, and cataclysmic variables) in addition to different classes of periodic and transient sources, using real data. We created a labeled set using various public catalogs (such as the Catalina Surveys and Gaia DR2 variable stars catalogs, and the Million Quasars catalog), and we classify all objects with ≥6 g-band or ≥6 r-band detections in ZTF (868,371 sources as of 2020 June 9), providing updated classifications for sources with new alerts every day. For the top level we obtain macro-averaged precision and recall scores of 0.96 and 0.99, respectively, and for the bottom level we obtain macro-averaged precision and recall scores of 0.57 and 0.76, respectively. Updated classifications from the light curve classifier can be found at the ALeRCE Explorer website (http://alerce.online).

47 OTHER INSTRUMENTATION↗
DOE OSTI2021

TESS Observations of the WASP-121 b Phase Curve

We study the red-optical photometry of the ultrahot Jupiter WASP-121 b as observed by the Transiting Exoplanet Survey Satellite (TESS) and model its atmosphere through a radiative transfer simulation. Given its short orbital period of ∼1.275 days, inflated state, and bright host star, WASP-121 b is exceptionally favorable for detailed atmospheric characterization. Toward this purpose, we use allesfitter to characterize its full red-optical phase curve, including the planetary phase modulation and secondary eclipse. We measure the day- and nightside brightness temperatures in the TESS passband as 3012{sub −42}{sup +40} and 2022{sub −602}{sup +254} K, respectively, and do not find a statistically significant phase shift between the brightest and substellar points. This is consistent with inefficient heat recirculation on the planet. We then perform an atmospheric retrieval analysis to infer the dayside atmospheric properties of WASP-121 b, such as its bulk composition, albedo, and heat recirculation. We confirm the temperature inversion in the atmosphere and suggest H{sup −}, TiO, and VO as potential causes of the inversion, absorbing heat at optical wavelengths at low pressures. Future Hubble Space Telescope and James Webb Space Telescope observations of WASP-121 b will benefit from its first full phase curve measured by TESS.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2021

Initial Characterization of Active Transitioning Centaur, P/2019 LD{sub 2} (ATLAS), Using Hubble, Spitzer, ZTF, Keck, Apache Point Observatory, and GROWTH Visible and Infrared Imaging and Spectroscopy

We present visible and mid-infrared imagery and photometry of temporary Jovian co-orbital comet P/2019 LD{sub 2} taken with Hubble Space Telescope/Wide Field Camera 3 (HST/WFC3), Spitzer Space Telescope/Infrared Array Camera (Spitzer/IRAC), and the GROWTH telescope network, visible spectroscopy from Keck/Low-Resolution Imaging Spectrometer (LRIS), and archival Zwicky Transient Facility observations taken between 2019 April and 2020 August. Our observations indicate that the nucleus of LD{sub 2} has a radius between 0.2 and 1.8 km assuming a 0.08 albedo and a coma dominated by ∼100 μm-scale dust ejected at ∼1 m s{sup −1} speeds with a ∼1′ jet pointing in the southwest direction. LD{sub 2} experienced a total dust mass loss of ∼10{sup 8} kg at a loss rate of ∼6 kg s{sup −1} with Afρ/cross section varying between ∼85 cm/125 km{sup 2} and ∼200 cm/310 km{sup 2} from 2019 April 9 to 2019 November 8. If the increase in Afρ/cross section remained constant, it implies LD{sub 2}'s activity began ∼2018 November when within 4.8 au of the Sun, implying the onset of H{sub 2}O sublimation. We measure CO/CO{sub 2} gas production of ≲10{sup 27} mol s{sup −1}/≲10{sup 26} mol s{sup −1} from our 4.5 μm Spitzer observations; g–r = 0.59 ± 0.03, r–i = 0.18 ± 0.05, and i–z = 0.01 ± 0.07 from GROWTH observations; and H{sub 2}O gas production of ≲80 kg s{sup −1} scaling from our estimated C {sub 2} production of Q{sub C{sub 2}}≲7.5×10{sup 24} mol s{sup −1} from Keck/LRIS spectroscopy. We determine that the long-term orbit of LD{sub 2} is similar to Jupiter-family comets having close encounters with Jupiter within ∼0.5 Hill radius in the last ∼3 y and within 0.8 Hill radius in ∼9 y. Additionally, 78.8% of our orbital clones are ejected from the solar system within 1 × 10{sup 6} yr, having a dynamical half-life of 3.4 × 10{sup 5} yr.

47 OTHER INSTRUMENTATION↗
DOE OSTI2021

Constraining the Nature of the PDS 70 Protoplanets with VLTI/GRAVITY

We present K-band interferometric observations of the PDS 70 protoplanets along with their host star using VLTI/GRAVITY. We obtained K-band spectra and 100 μas precision astrometry of both PDS 70 b and c in two epochs, as well as spatially resolving the hot inner disk around the star. Rejecting unstable orbits, we found a nonzero eccentricity for PDS 70 b of 0.17 ± 0.06, a near-circular orbit for PDS 70 c, and an orbital configuration that is consistent with the planets migrating into a 2:1 mean motion resonance. Enforcing dynamical stability, we obtained a 95% upper limit on the mass of PDS 70 b of 10 M {sub Jup}, while the mass of PDS 70 c was unconstrained. The GRAVITY K-band spectra rules out pure blackbody models for the photospheres of both planets. Instead, the models with the most support from the data are planetary atmospheres that are dusty, but the nature of the dust is unclear. Any circumplanetary dust around these planets is not well constrained by the planets’ 1–5 μm spectral energy distributions (SEDs) and requires longer wavelength data to probe with SED analysis. However with VLTI/GRAVITY, we made the first observations of a circumplanetary environment with sub-astronomical-unit spatial resolution, placing an upper limit of 0.3 au on the size of a bright disk around PDS 70 b.

47 OTHER INSTRUMENTATION↗
DOE OSTI2021

A Multiwavelength Look at the GJ 9827 System: No Evidence of Extended Atmospheres in GJ 9827b and d from HST and CARMENES Data

GJ 9827 is a bright star hosting a planetary system with three transiting planets. As a multiplanet system with planets that sprawl within the boundaries of the radius gap between terrestrial and gaseous planets, GJ 9827 is an optimal target to study the evolution of the atmospheres of close-in planets with a common evolutionary history and their dependence from stellar irradiation. Here we report on the Hubble Space Telescope (HST) and CARMENES transit observations of GJ 9827 planets b and d. We performed a stellar and ISM characterization from the ultraviolet HST spectra, obtaining fluxes for Lyα and Mg ii of F(Lyα) = (5.42{sub −0.75}{sup +0.96}) × 10{sup −13} erg cm{sup −2} s{sup −1} and F(Mgii) = (5.64 ± 0.24) × 10{sup −14} erg cm{sup −2} s{sup −1}. We also investigated a possible absorption signature in Lyα in the atmosphere of GJ 9827b during a transit event from HST spectra, as well as Hα and He i signature for the atmosphere of GJ 9827b and d from CARMENES spectra. We found no evidence of an extended atmosphere in either of the planets. This result is also supported by our analytical estimations of mass loss based on the measured radiation fields for all three planets of this system, which led to a mass-loss rate of 0.4, 0.3, and 0.1 planetary masses per Gyr for GJ 9827b, c, and d, respectively. These values indicate that the planets could have lost their volatiles quickly in their evolution and probably do not retain an atmosphere at the current stage.

47 OTHER INSTRUMENTATION↗
DOE OSTI2021

Use of Multi-Site Radiation Therapy for Systemic Disease Control

Metastatic cancer is a heterogeneous entity, some of which could benefit from local consolidative radiation therapy (RT). Although randomized evidence is growing in support of using RT for oligometastatic disease, a highly active area of investigation relates to whether RT could benefit patients with polymetastatic disease. This article highlights the preclinical and clinical rationale for using RT for polymetastatic disease, proposes an exploratory framework for selecting patients best suited for these types of treatments, and briefly reviews potential challenges. The goal of this hypothesis-generating review is to address personalized multimodality systemic treatment for patients with metastatic cancer. The rationale for using high-dose RT is primarily for local control and immune activation in either oligometastatic or polymetastatic disease. However, the primary application of low-dose RT is to activate distinct antitumor immune pathways and modulate the tumor stroma in efforts to better facilitate T cell infiltration. We explore clinical cases involving high- and low-dose RT to demonstrate the potential efficacy of such treatment. We then group patients by extent of disease burden to implement high- and/or low-dose RT. Patients with low-volume disease may receive high-dose RT to all sites as part of an oligometastatic paradigm. Subjects with high-volume disease (for whom standard of care remains palliative RT only) could be treated with a combination of high-dose RT to a few sites for immune activation, while receiving low-dose RT to several remaining lesions to enhance systemic responses from high-dose RT and immunotherapy. We further discuss how emerging but speculative concepts such as immune function may be integrated into this approach and examine therapies currently under investigation that may help address immune deficiencies. The review concludes by addressing challenges in using RT for polymetastatic disease, such as concerns about treatment planning workflows, treatment times, dose constraints for multiple-isocenter treatments, and economic considerations.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Do Coordinated Knowledge Translation Campaigns Persuade Radiation Oncologists to Use Single-Fraction Radiation Therapy Compared With Multiple-Fraction Radiation Therapy for Bone Metastases?

Although level 1 evidence supports the use of single-fraction radiation therapy (SFRT) compared with multiple-fraction radiation therapy (MFRT) for the palliative management of bone metastases, SFRT is underused. In early 2017, the Canadian Partnership Against Cancer and CancerCare Manitoba undertook a comprehensive knowledge translation campaign in Manitoba, Canada featuring educational outreach visits, local consensus meetings, and audit and feedback interventions to encourage greater use of SFRT. This study assessed the impact of this campaign on SFRT use and identified variables associated with MFRT usage.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

NRG Oncology/RTOG Consensus Guidelines for Delineation of Clinical Target Volume for Intensity Modulated Pelvic Radiation Therapy in Postoperative Treatment of Endometrial and Cervical Cancer: An Update

Accurate target definition is critical for the appropriate application of radiation therapy. In 2008, the Radiation Therapy Oncology Group (RTOG) published an international collaborative atlas to define the clinical target volume (CTV) for intensity modulated pelvic radiation therapy in the postoperative treatment of endometrial and cervical cancer. The current project is an updated consensus of CTV definitions, with removal of all references to bony landmarks and inclusion of the para-aortic and inferior obturator nodal regions.

62 RADIOLOGY AND NUCLEAR MEDICINE↗