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All sources NASA NTRS DOE OSTI

DOE OSTI2021

Biodiversity and Global Health: Intersection of Health, Security, and the Environment

One of the biggest consequences of large-scale environmental change is the loss of biodiversity. Recent studies predict a loss of 1 million species in the near future. Biodiversity loss and land use change through anthropogenic disturbance are known to affect disease exposure, disease severity, and disease impacts. It is becoming increasingly clear that biodiversity loss will lead to an increase in infectious diseases in certain regions. Changes in biodiversity may contain important signatures for prediction of infectious diseases and outbreaks. Here, we argue that areas of high or rapid biodiversity loss will be critical to monitor under the umbrella of global health security. Global Health Security consists of the actions and activities required to reduce the impact of public health events in populations living in different geographic regions and across international borders. Like infectious diseases, climate change and other causes of environmental changes do not respect international borders and are becoming more widespread in all parts of the world. Here, the relationships among biodiversity, climate and environmental changes, and pathogen prevalence are dynamic, context dependent, and complex. Accounting for this complexity requires the inclusion of the environment sector, presently missing, when evaluating the potential of global health security actions for mitigating disease risks.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2003

Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters

Loss-of-function mutations of gap junction proteins, connexins, represent a mechanism of disease in a variety of tissues. We have shown that recessive (gene deletion) or dominant (connexin45 overexpression) disruption of connexin43 function results in osteoblast dysfunction and abnormal expression of osteoblast genes, including down-regulation of osteocalcin transcription. To elucidate the molecular mechanisms of gap junction-sensitive transcriptional regulation, we systematically analyzed the rat osteocalcin promoter for sensitivity to gap junctional intercellular communication. We identified an Sp1/Sp3 containing complex that assembles on a minimal element in the -70 to -57 region of the osteocalcin promoter in a gap junction-dependent manner. This CT-rich connexin-response element is necessary and sufficient to confer gap junction sensitivity to the osteocalcin proximal promoter. Repression of osteocalcin transcription occurs as a result of displacement of the stimulatory Sp1 by the inhibitory Sp3 on the promoter when gap junctional communication is perturbed. Modulation of Sp1/Sp3 recruitment also occurs on the collagen Ialpha1 promoter and translates into gap junction-sensitive transcriptional control of collagen Ialpha1 gene expression. Thus, regulation of Sp1/Sp3 recruitment to the promoter may represent a potential general mechanism for transcriptional control of target genes by signals passing through gap junctions.

Non-NASA Center↗

DOE OSTI2022

Prevalence and scalable control of localized networks

The ability to control network dynamics is essential for ensuring desirable functionality of many technological, biological, and social systems. Such systems often consist of a large number of network elements, and controlling large-scale networks remains challenging because the computation and communication requirements increase prohibitively fast with network size. Here, we introduce a notion of network locality that can be exploited to make the control of networks scalable, even when the dynamics are nonlinear. We show that network locality is captured by an information metric and is almost universally observed across real and model networks. In localized networks, the optimal control actions and system responses are both shown to be necessarily concentrated in small neighborhoods induced by the information metric. This allows us to develop localized algorithms for determining network controllability and optimizing the placement of driver nodes. This also allows us to develop a localized algorithm for designing local feedback controllers that approach the performance of the corresponding best global controllers, while incurring a computational cost orders-of-magnitude lower. Here, we validate the locality, performance, and efficiency of the algorithms in Kuramoto oscillator networks, as well as three large empirical networks: synchronization dynamics in the Eastern US power grid, epidemic spreading mediated by the global air-transportation network, and Alzheimer’s disease dynamics in a human brain network. Taken together, our results establish that large networks can be controlled with computation and communication costs comparable to those for small networks.

42 ENGINEERING↗

NASA NTRS2009

Operations to Research: Communication of Lessons Learned

This presentation explores ways to build upon previous spaceflight experience and communicate this knowledge to prepare for future exploration. An operational approach is highlighted, focusing on selection and retention standards (disease screening and obtaining medical histories); pre-, in-, and post-flight monitoring (establishing degrees of bone loss, skeletal muscle loss, cardiovascular deconditioning, medical conditions, etc.); prevention, mitigation, or treatment (in-flight countermeasures); and, reconditioning, recovery, and reassignment (post-flight training regimen, return to pre-flight baseline and flight assignment). Experiences and lessons learned from the Apollo, Skylab, Shuttle, Shuttle-Mir, International Space Station, and Orion missions are outlined.

Fogarty, Jennifer↗

NASA NTRS1991

Satellite, environmental, and medical information applied to epidemiological monitoring

Improved communications and space-science technologies, such as remote sensing, offer hope of new, more holistic approaches to combating many arthropod-borne disease problems. The promise offered by these technologies has surfaced at a time when global and national efforts at disease control are in decline. Indeed, these programs seem to be losing ground against the arthropod-borne diseases just as rapidly as we seem to be moving forward in technological development. Given these circumstances, we can only hope that remote sensing and geographic information system (GIS) technologies can be pressed into service to help target the temporal and spatial application of control measures and to help in developing new control strategies.

Roberts, Donald R.↗

DOE OSTI2020

Converting Clinical Pathways to BPM+ Standards: A Case Study in Stable Ischemic Heart Disease

Clinical pathways (CPs) are structured healthcare plans designed to implement evidence-based clinical guidelines, medical algorithms, and protocols. In recent years, a community called BPM+ Health has worked to establish a shareable and computer-consumable representation of CP, leveraging standard notations. These notations, collectively referred to as BPM+, include the Business Process Management and Notation (BPMN), Case Management Model and Notation (CMMN), and Decision Model and Notation (DMN), which aim to support clinical management and standardized communication between different stakeholders. However, the adaptation of these notations for the existing guidelines has largely been left unexplored. This paper introduces procedural steps and criteria considerations to apply components of BPM+ notations to reconstruct a guideline for Stable Ischemic Heart Disease. This paper describes how each of the three different notations is mapped to a medical guideline and discusses the advantages and limitations of representing CPs with BPM+ as compared with paper-based medical guidelines.

Chae, Junghoon↗

DOE OSTI2022

Microbial sensor system for monitoring and imaging of an environment

A microbial sensor, microbial sensing system, and method that can be used to determine the chemical environment of unsaturated soils, rhizosphere, and/or plants are disclosed. The microbial sensing system can be used for monitoring the health of plants including nutrients, salinity, contaminants, chemicals (pesticides, herbicides) and diseases. A microbial sensing system can include one or more indicator electrodes and a reference electrode. The microbial sensing system can include a signal acquisition and/or communication module to allow the real-time collection of data from field deployments and laboratory investigations.

Burge, Scott R.↗

NASA NTRS2016

Risk of Adverse Health Outcomes & Decrements in Performance due to Inflight Medical Conditions: ExMC Pharmacy Research Plan

The Exploration Medical Capabilities (ExMC) Element of NASA's Human Research Program is charged with identifying medical capabilities that can address the challenges of prevention, diagnosis, and treatment of disease and injuries that could occur during exploration missions beyond Earth's orbit. Faced with the obstacle of access to in-flight medical care, and limitations of vehicle space, time, and communications; it is necessary to prioritize what medical consumables are manifested for the flight, and which medical conditions are addressed. Studies of astronaut health establish the incidence of common and high risk medical conditions that require medical intervention during long-duration exploration missions. In 2000, the Institute of Medicine (IOM) convened a committee of experts, Committee on Creating a Vision for Space Medicine during Travel beyond Earth Orbit, to examine the issues surrounding astronaut health and safety for long duration space missions. Two themes run throughout the committee's final report: (1) that not enough is known about the risks to human health during long-duration missions beyond Earth's orbit or about what can effectively mitigate those risks to enable humans to travel and work safely in the environment of deep space and (2) that everything reasonable should be done to gain the necessary information before humans are sent on missions of space exploration (IOM, 2001). Although several spaceflight focused pharmaceutical research studies have been conducted, few have provided sufficient data regarding medication usage or potency changes during spaceflight. The Du pharmaceutical stability study assessed medications flown on space shuttles to and from the International Space Station (ISS) from 2006 until 2008; of which some medications were still viable beyond their expiration dates (Du et al, 2011). However, as with many spaceflight studies, the small 'n' associated with this study limits the ability to draw strong conclusions from it. Dr. Wotring and others have recently published articles containing information regarding medication usage, indications, and efficacy gleaned from spaceflight records (Wotring et al, 2015, 2016; Barger et al, 2014; Basner and Dinges, 2014). Although some conclusions can be drawn from these studies, the inability to fully quantify medication usage, indications, side effects, and effectiveness, limits insight as to which medications should be prioritized for further research.

Antonsen, Erik↗

DOE OSTI2020

Non-coding RNAs: update on mechanisms and therapeutic targets from the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart

Abstract Vast parts of mammalian genomes are actively transcribed, predominantly giving rise to non-coding RNA (ncRNA) transcripts including microRNAs, long ncRNAs, and circular RNAs among others. Contrary to previous opinions that most of these RNAs are non-functional molecules, they are now recognized as critical regulators of many physiological and pathological processes including those of the cardiovascular system. The discovery of functional ncRNAs has opened up new research avenues aiming at understanding ncRNA-related disease mechanisms as well as exploiting them as novel therapeutics in cardiovascular therapy. In this review, we give an update on the current progress in ncRNA research, particularly focusing on cardiovascular physiological and disease processes, which are under current investigation at the ESC Working Groups of Myocardial Function and Cellular Biology of the Heart. This includes a range of topics such as extracellular vesicle-mediated communication, neurohormonal regulation, inflammation, cardiac remodelling, cardio-oncology as well as cardiac development and regeneration, collectively highlighting the wide-spread involvement and importance of ncRNAs in the cardiovascular system.

Bär, Christian↗

DOE OSTI2026

Developing Scenario‐Based Strategies for Health, Climate, and Environmental Preparedness: The One Health, One Earth Approach

Climate change amplifies many threats to human health. Despite advances in understanding climate change dynamics and impacts, there remains a critical gap in translating scientific knowledge into equitable, and community-driven health interventions. The inaugural One Earth, One Health workshop sought to explore this gap through human-centered design exercises involving interdisciplinary researchers from climate and Earth sciences, engineering, epidemiology, microbiology, and environmental health. Although participants did not co-develop solutions with affected communities, they used stakeholder role-playing to guide ideation and lay groundwork for actionable plans. Through these methods, participants identified community needs and proposed prototype solutions to alleviate health threats exacerbated by global environmental change. Prototypes were organized around infectious diseases, extreme weather, and air quality, as illustrative themes rather than an exhaustive set of risks. Key solutions included strategies for anticipatory systems and early warning (e.g., integrating environmental signals with health data), inclusive communication and infrastructure needs for responding to extreme weather events, and integrated platforms visualizing air quality trends to support tailored, context-aware guidance beyond one-size-fits-all alerts. The workshop highlighted opportunities such as leveraging machine learning, Earth observation, and real-time surveillance to protect communities, but also noted barriers including data quality, technological redundancy, privacy, and governance challenges. Additionally, participants emphasized the need for interdisciplinary teams capable of collaborating across sectors, breaking down silos and addressing gaps in training and education. Overall, the workshop illustrates how process-driven, human-centered approaches can help surface user needs and generate testable prototype concepts, while underscoring the importance of direct community partnership for implementation.

Abadi, Azar M. [University of Alabama, Birmingham,↗

NASA NTRS2010

Atrial Fibrillation During an Exploration Class Mission

Background: A long-duration exploration class mission is fraught with numerous medical contingency plans. Herein, we explore the challenges of symptomatic atrial fibrillation (AF) occurring during an exploration class mission. The actions and resources required to ameliorate the situation, including the availability of appropriate pharmaceuticals, monitoring devices, treatment modalities, and communication protocols will be investigated. Challenges of Atrial Fibrillation during an Exploration Mission: Numerous etiologies are responsible for the initiation of AF. On Earth, we have the time and medical resources to evaluate and determine the causative situation for most cases of AF and initiate therapy accordingly. During a long-duration exploration class mission resources will be severely restricted. How is one to determine if new onset AF is due to recent myocardial infarction, pulmonary embolism, fluid overload, thyrotoxicosis, cardiac structural abnormalities, or CO poisoning? Which pharmaceutical therapy should be initiated and what potential side effects can be expected? Should anti-coagulation therapy be initiated? How would one monitor the therapeutic treatment of AF in microgravity? What training would medical officers require, and which communication strategies should be developed to enable the best, safest therapeutic options for treatment of AF during a long-duration exploration class mission? Summary: These questions will be investigated with expert opinion on disease elucidation, efficient pharmacology, therapeutic monitoring, telecommunication strategies, and mission cost parameters with emphasis on atrial fibrillation being just one illustration of the tremendous challenges that face a long-duration exploration mission. The limited crew training time, medical hardware, and drugs manifested to deal with such an event predicate that aggressive primary and secondary prevention strategies be developed to protect a multibillion-dollar asset like the International Space Station or a mission to the Moon or Mars. Learning Objectives: The audience will become familiar with the risks and challenges inherent to developing a therapeutic strategy for the treatment of atrial fibrillation during a long-term exploration class mission.

Lipset, Mark A.↗

DOE OSTI2022

Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling

Background: Type 1 diabetes (T1D) is a complex autoimmune disorder whose pathogenesis involves an intricate interplay between ß cells of the pancreatic islet, other islet cells, and cells of the immune system. Direct intercellular communication within the islet occurs via cell surface proteins and indirect intercellular communication has traditionally been as occurring via secreted proteins (e.g., endocrine hormones and cytokines). However, recent literature suggests that extracellular vesicles (EVs) secreted by ß cells constitute an additional and biologically important mechanism for transmitting signals to adjacent ß cells or immune cells. Scope of Review: This review summarizes the general mechanisms of EV formation, with a particular focus on how lipids and lipid signaling pathways influence their formation and cargo. We review the implications of EV release from ß cells for T1D pathogenesis, how EVs and their cargo might be leveraged as biomarkers of the early events leading to T1D, and how EVs might be engineered as a therapeutic candidate to counter T1D outcomes. Major Conclusions: Islet ß cells have been viewed as initiators and propagators of the cellular circuit giving rise to autoimmunity in T1D. In this context, emerging literature suggests that EVs may represent a conduit for communication that holds more comprehensive messaging about the ß cells from which they arise. As the field of EV biology advances, it opens the possibility that intervening with EV formation and cargo loading could be a novel disease-modifying approach in T1D.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

NASA NTRS1987

A PC-Based Free Text DSS for Health Care

A free Decision Support System(DST) has been constructed for health care professional that allows the analysis of complex medical cases and the creation of diagnostic list of potential diseases for clinical evaluation.The system uses a PC-based text management system specifically designed for desktop operation. The texts employed in the decision support package include the Merck Manual (published by Merck Sharpe & Dohme) and Control of Communicable Diseas in Man (published by the American Public Health Association). The background and design of the database are discussed along with a structured analysis procedure for handling free text DSS system. A case study is presented to show the application of this technology and conclusions are drawn in the summary that point to expanded areas of professional intention and new frontiers yet to be explored in this rapidly progressing field.

Grams, Ralph R.↗

NASA NTRSDate not supplied

The Cosmic Radiation Symphony: Soundtrack for a Journey to Mars

Space radiation (SR) is a constant threat to astronauts who journey away from the Earth’s protective magnetosphere. Galactic cosmic rays (GCR) are atomic nuclei from remnants of supernovae and are omnipresent in outer space. These ionized particles travel close to the speed of light and when they traverse biological material,they leave behind a path of damage. Another space radiation threat is from our sun when solar particle events (SPEs), or bursts of energetic protons,occur. Exposure to space radiation can lead to cancer, cardiovascular disease,immune dysfunction, and cognitive and behavioral decrements. Yet humans cannot see, smell, taste, hear,or feel radiation, making it less tangible than other health threats and much more difficult to describe.This is an important gap in risk communication that the Space Radiation Element is working to close within NASA’s Human Research Program. Music and art are powerful means of communicating human emotions and feelings and are effective and creative ways to convey other types of information. In this work, the sonification process was used to transcribe or translate the physical nature of the SR environment on a 3-year mission to Mars into sound, a format perceptible to the human ear. A visual representation for the journey was also developed so the audience can both hear and envision the chronic presence of GCR and the acute and large bursts of energy present in SPEs. Data for this project were derived from the Radiation Assessment Detector on the NASA Curiosity Rover during its outbound cruise to Mars and on the Martian surface, as well as from models of the space radiation environment behind spacecraft shielding. Our data-driven audiovisual composition was realized using custom programmed digital signal processing and graphic design in the programming languages Pure Data and Processing. The data sonification was contextualized in time and space by calculating and visualizing the location of the spacecraft in relation to the other planets during the Mars mission. The finished work is a unique and powerful means of communicating the presence and risk of space radiation, accessible by people of all ages and scientific backgrounds

Richard Snow↗

NASA NTRS2014

Monitors Enable Medication Management in Patients' Homes

Glenn Research Center awarded SBIR funding to ZIN Technologies to develop a platform that could incorporate sensors quantifying an astronaut’s health status and then communicate with the ground. ZIN created a device, developed the system further, and then formed Cleveland-based FlexLife Health to commercialize the technology. Today it is part of an anti-coagulation management system for people with cardiovascular disease.

Source record↗

NASA NTRS2020

Credible practice of modeling and simulation in healthcare: ten rules from a multidisciplinary perspective

The complexities of modern biomedicine are rapidly increasing. Thus, modeling and simulation have become increasingly important as a strategy to understand and predict the trajectory of pathophysiology, disease genesis, and disease spread in support of clinical and policy decisions. In such cases, inappropriate or ill-placed trust in the model and simulation outcomes may result in negative outcomes, and hence illustrate the need to formalize the execution and communication of modeling and simulation practices. Although verification and validation have been generally accepted as significant components of a model’s credibility, they cannot be assumed to equate to a holistic credible practice, which includes activities that can impact comprehension and in-depth examination inherent in the devel-opment and reuse of the models. For the past several years, the Committee on Credible Practice of Modeling and Simulation in Healthcare, an interdisciplinary group seeded from a U.S. interagency initiative, has worked to codify best practices. Here, we provide Ten Rules for credible practice of modeling and simulation in healthcare developed from a comparative analysis by the Committee’s multidisciplinary membership, followed by a large stakeholder com-munity survey. These rules establish a unified conceptual framework for modeling and simulation design, implementation, evaluation, dissemination and usage across the modeling and simulation life-cycle. While biomedical science and clinical care domains have somewhat different requirements and expectations for credible practice, our study converged on rules that would be useful across a broad swath of model types. In brief, the rules are: (1) Define context clearly. (2) Use contextually appropriate data. (3) Evaluate within context. (4) List limitations explicitly. (5) Use version control. (6) Document appropriately. (7) Disseminate broadly. (8) Get independent reviews. (9) Test competing imple-mentations. (10) Conform to standards. Although some of these are common sense guidelines, we have found that many are often missed or misconstrued, even by seasoned practitioners. Computational models are already widely used in basic science to generate new biomedical knowledge. As they penetrate clinical care and healthcare policy, contributing to personalized and precision medicine, clinical safety will require established guidelines for the credible practice of modeling and simulation in healthcare.

Credibility↗

NASA NTRS2010

Influence of Ionizing Radiation on Stromal-Epithelial Intercellular Communication in Esophageal Carcinogenesis

Esophageal cancer is the 6th leading cause of cancer death worldwide. Its development is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. An association with ionizing radiation exposure is revealed by the high excess relative risk for squamous cell carcinoma of the esophagus observed in the survivors of the atomic bomb detonations in Japan. It is also seen as a secondary malignancy in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely curable. The stromal microenvironment plays an essential role in the maintenance and modulation of normal epithelial cell growth and differentiation and cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibroblasts (Okawa et al., Genes & Dev. 2007. 21: 2788-2803). We examined how radiation treatment of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. Chemotactic and haptotactic migration of epithelial cells stimulated by conditioned media from irradiated fibroblasts was measured using assays conducted in Transwell cell culture chambers. Our results using low LET radiation showed a dose-dependent increase in migration of epithelial cells when exposed to conditioned media from irradiated vs. non-irradiated fibroblasts. We also observed enhanced invasion through a basement membrane simulant. To identify chemotactic proteins secreted by irradiated stromal fibroblasts, we used antibody capture cytokine arrays and have identified several proteins as candidates. Increased secretion of these factors by irradiated fibroblasts was confirmed using ELISA. We are currently analyzing the contribution of these individual factors on epithelial migration and invasion, as well as their influence on cell survival and DNA repair. Studies using high-LET radiation will help determine radiation quality effects on these processes. These results should further our understanding of the mechanisms by which radiation impacts the tissue microenvironment and how it influences cancer development processes.

Patel, Zarana S.↗

NASA NTRS2006

Towards Biological Inspiration in the Development of Complex Systems

Greater understanding of biology in modem times has enabled significant breakthroughs in improving healthcare, quality of life, and eliminating many diseases and congenital illnesses. Simultaneously there is a move towards emulating nature and copying many of the wonders uncovered in biology, resulting in "biologically inspired" systems. Significant results have been reported in a wide range of areas, with systems inspired by nature enabling exploration, communication, and advances that were never dreamed possible just a few years ago. We warn, that as in many other fields of endeavor, we should be inspired by nature and biology, not engage in mimicry. We describe some results of biological inspiration that augur promise in terms of improving the safety and security of systems, and in developing self-managing systems, that we hope will ultimately lead to self-governing systems.

Hinchey, Michael G.↗