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At least 541 records · Page 30

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DOE OSTI2024

Sex Differences in Odds of Brain Metastasis and Outcomes by Brain Metastasis Status after Advanced Melanoma Diagnosis

Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011–30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Analyzing BMP2, FGFR, and TGF Beta Expressions in High-Grade Osteosarcoma Untreated and Treated Autografts Using Proteomic Analysis

In the last few decades, biological reconstruction techniques have improved greatly for treating high-grade osteosarcoma patients. To conserve the limb, and its function the affected tumor-bearing bones have been treated using liquid nitrogen and irradiation processes that enable the removal of entire tumors from the bone, and these treated autografts can be reconstructed for the patients. Here, we focus on the expressions of the growth factor family proteins from the untreated and treated autografts that play a crucial role in bone union, remodeling, and regeneration. In this proteomic study, we identify several important cytoskeletal, transcriptional, and growth factor family proteins that showed substantially low levels in untreated autografts. Interestingly, these protein expressions were elevated after treating the tumor-bearing bones using liquid nitrogen and irradiation. Therefore, from our preliminary findings, we chose to determine the expressions of BMP2, TGF-Beta, and FGFR proteins by the target proteomics approach. Using a newly recruited validation set, we successfully validate the expressions of the selected proteins. Furthermore, the increased growth factor protein expression after treatment with liquid nitrogen may contribute to bone regeneration healing, assist in faster recovery, and reduce local recurrence and metastatic spread in high-grade sarcoma patients.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Molecular and Genetic Characterization of Hepatitis B Virus (HBV) among Saudi Chronically HBV-Infected Individuals

The study aimed to characterize the genotype and subgenotypes of HBV circulating in Saudi Arabia, the presence of clinically relevant mutations possibly associated with resistance to antivirals or immune escape phenomena, and the possible impact of mutations in the structural characteristics of HBV polymerase. Plasma samples from 12 Saudi Arabian HBV-infected patients were analyzed using an in-house PCR method and direct sequencing. Saudi patients were infected with mainly subgenotype D1. A number of mutations in the RT gene (correlated to antiviral resistance) and within and outside the major hydrophilic region of the S gene (claimed to influence immunogenicity and be related to immune escape) were observed in almost all patients. Furthermore, the presence of mutations in the S region caused a change in the tertiary structure of the protein compared with the consensus region. Clinical manifestations of HBV infection may change dramatically as a result of viral and host factors: the study of mutations and protein-associated cofactors might define possible aspects relevant for the natural and therapeutic history of HBV infection.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Commitment to Hypertension Control During the COVID-19 Pandemic: Million Hearts Initiative Exemplars

Hypertension is a major risk factor for cardiovascular diseases, but 3 of 4 US adults do not have their blood pressure adequately controlled. Million Hearts (US Department of Health and Human Services) is a national initiative that promotes a set of priorities and interventions to optimize delivery of evidence-based strategies to manage cardiovascular disease, including hypertension. The COVID-19 pandemic, however, has disrupted routine care and preventive service delivery. We identified examples of clinical and health organizations that adapted services and care processes to continue a focus on monitoring and controlling hypertension during the pandemic. Eight Hypertension Control Exemplars were identified and interviewed. They reported various adapted care strategies including telemedicine, engaging patients in self-measured blood pressure monitoring, adapting or implementing medication management services, activating partnerships to respond to patient needs or expand services, and implementing unique patient outreach approaches. Documenting these hypertension control strategies can help increase adoption of adaptive approaches during public health emergencies and routine care.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Modeling hepatitis C virus kinetics during liver transplantation highlights the role of the liver in virus clearance

While the liver, specifically hepatocytes, are widely accepted as the main source of hepatitis C virus (HCV) production, the role of the liver/hepatocytes in clearance of circulating HCV remains unknown. Frequent HCV kinetic data were recorded and mathematically modeled from five liver transplant patients throughout the anhepatic (absence of liver) phase and for 4 hr post-reperfusion. During the anhepatic phase, HCV remained at pre-anhepatic levels (n = 3) or declined (n = 2) with t 1/2 ~1 hr. Immediately post-reperfusion, virus declined in a biphasic manner in four patients consisting of a rapid decline (t 1/2 = 5 min) followed by a slower decline (t 1/2 = 67 min). Consistent with the majority of patients in the anhepatic phase, when we monitored HCV clearance at 37°C from culture medium in the absence/presence of chronically infected hepatoma cells that were inhibited from secreting HCV, the HCV t 1/2 in cell culture was longer in the absence of chronically HCV-infected cells. The results suggest that the liver plays a major role in the clearance of circulating HCV and that hepatocytes may be involved.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses

Cytokines elicit pleiotropic and non-redundant activities despite strong overlap in their usage of receptors, JAKs and STATs molecules. We use IL-6 and IL-27 to ask how two cytokines activating the same signaling pathway have different biological roles. We found that IL-27 induces more sustained STAT1 phosphorylation than IL-6, with the two cytokines inducing comparable levels of STAT3 phosphorylation. Mathematical and statistical modeling of IL-6 and IL-27 signaling identified STAT3 binding to GP130, and STAT1 binding to IL-27Rα, as the main dynamical processes contributing to sustained pSTAT1 levels by IL-27. Mutation of Tyr613 on IL-27Rα decreased IL-27-induced STAT1 phosphorylation by 80% but had limited effect on STAT3 phosphorgylation. Strong receptor/STAT coupling by IL-27 initiated a unique gene expression program, which required sustained STAT1 phosphorylation and IRF1 expression and was enriched in classical Interferon Stimulated Genes. Interestingly, the STAT/receptor coupling exhibited by IL-6/IL-27 was altered in patients with systemic lupus erythematosus (SLE). IL-6/IL-27 induced a more potent STAT1 activation in SLE patients than in healthy controls, which correlated with higher STAT1 expression in these patients. Partial inhibition of JAK activation by sub-saturating doses of Tofacitinib specifically lowered the levels of STAT1 activation by IL-6. Our data show that receptor and STATs concentrations critically contribute to shape cytokine responses and generate functional pleiotropy in health and disease.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Response to comment on ‘SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung’

Early in the SARS-CoV-2 pandemic, we compared transcriptome data from hospitalized COVID-19 patients and control patients without COVID-19. We found changes in procoagulant and fibrinolytic gene expression in the lungs of COVID-19 patients. These findings have been challenged based on issues with the samples. We have revisited our previous analyses in the light of this challenge and find that these new analyses support our original conclusions.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

The State of Virtual Healthcare

In recent years, telehealth or telemedicine has become an integral component of health systems. During the COVID-19 pandemic, telehealth became the primary route of treatment for patients and doctors. The goals of telehealth are to make healthcare more accessible to patients who have limited mobility, time, or transportation options and those who live in rural or isolated communities. Telehealth aims to improve coordination and care between healthcare teams and their patients. While addressing accessibility, telehealth sets health systems on a path to meet their decarbonization and energy reduction goals. The document provides insights and best practices for telehealth, including carbon reduction, space utilization, equitable access, and technology.

Better Buildings, telehealth, carbon footprint↗

DOE OSTI2022

Methods for cytotoxic chemotherapy-based predictive assays

The invention relates to methods, systems and kits for determining therapeutic effectiveness or toxicity of cancer-treating compounds that incorporate into or bind to DNA. In particular, the invention is directed to methods, systems and kits for predicting a patient's treatment outcome after administration of a microdose of therapeutic composition to the patient. The methods provides physicians with a diagnostic tool to segregate cancer patients into differential populations that have a higher or lower chance of responding to a particular therapeutic treatment.

Henderson, Paul↗

DOE OSTI2021

Using occupant interaction with advanced lighting systems to understand opportunities for energy optimization: Control data from a hospital NICU

For this study, lighting system control data from five patient rooms in a neonatal intensive care unit (NICU) over a 25-week monitoring period were analyzed to better understand how the NICU staff and families interacted with an automatic tunable lighting system (variable spectrum and intensity) with manual override options. The data were analyzed to determine the amount of time spent in available lighting modes, estimate energy consumption, and to observe any patterns in how the lighting system was being used by occupants. Further analysis revealed opportunities for optimizing the system for occupant needs and energy savings. The patient room occupants were clearly engaged in using the lighting system throughout the 24-hour day to meet needs and preferences. Giving occupants control over the lighting system did not result in a considerable increase in energy use. Implementing a time-out would minimize the extended periods of time when the lights were left on without need at the highest brightness level, further decreasing energy use. This analysis reveals the potential of lighting control data to contribute to energy savings.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

DOE OSTI2021

The Role of Circulating Tumor Cells in Breast Cancer and Implications for Radiation Treatment Decisions

Tumor biomarkers are used routinely in oncology to assign risk categorization, screen and assist in diagnosis of malignancy, allow for prognostication and prediction of outcomes and treatment response, and allow for monitoring of patients after treatment completion. Although tissue-based biomarkers have a long history of use, the emergence of liquid-based biomarkers, including circulating tumor cells (CTCs), may soon revolutionize the management of patients with cancer. Here, we review the discovery of CTCs and their role as prognostic and predictive biomarkers, with an emphasis on breast cancer. We discuss the platforms for CTC enumeration and focus on studies using the only US Food and Drug Administration–approved platform for CTC enumeration (CellSearch). In addition, we examine the role of CTCs in women with metastatic, inflammatory, and nonmetastatic breast cancer, as well as the clinical evidence for their use as a surrogate for radiation treatment response as well as surveillance after treatment. Finally, we conclude by investigating ongoing clinical studies assessing CTCs as radiation response predictors and discuss unanswered questions.