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At least 361 records · Page 20

The Evolution of the Impact Evidence Library Methods – What We Learned

During fiscal years 2020-2022 NASA’s Human Research Program, Exploration Medical Capability Element has worked to source this evidence for the model. During the process several lessons learned have been identified and drive recommendations for future efforts. The ICL 1.0: Spaceflight Medical Operational expertise should be consulted regarding the addition of future conditions. A clinician experienced with the nuances of spaceflight is recommended to have a minimum of 20 hours per condition to adequately source the evidence. Condition definitions should be carefully crafted to maintain mutual exclusivity. Common side effects from medications, common and consequential incidental findings in laboratory studies, and consequential side effects of diagnostic and procedural capabilities should be considered for inclusion as unique conditions in future iterations of the ICL 1.0. Incidence: Spaceflight incidence, although based on small population sizes, is the gold standard. Terrestrial incidence should be applied cautiously. Probability of minor vs. severe cases of the condition: Data informing severity probability of the medical condition are nearly always terrestrial. Special attention should be paid to this metric as it drives outcomes in the model and terrestrial data often overestimate severity of expected cases in spaceflight. Condition duration: Three clinical phases currently exist in the model. They represent the time necessary for diagnosis, treatment/convalescence/recurrence, and the remaining duration of the mission after maximal recovery, respectively. Further subdivision of acute and convalescent treatment/recurrence is recommended. Probability of need for evacuation: Surrogates for “Return to Definitive Care” were chosen prior to data collection. In most cases these surrogates were “need for hospitalization” or “need for surgery.” For many conditions these may not be realistic drivers of “Return to Definitive Care” and should be re-examined. Probability of Crew Mortality: Terrestrial mortality data is difficult to apply to astronauts who, invariably, have less comorbidities than terrestrial subjects. It must be applied judiciously. The proportion of mission tasks impaired by the condition: “Task Impairment” was assigned to each condition prior to the condition duration data becoming available. Future efforts should assign Task Impairment as the final step in sourcing the evidence.

A.J. Kreykes↗

Harnessing Artificial Intelligence for Medical Diagnosis and Treatment During Space Exploration Missions

BACKGROUND The medical capabilities necessary for long-duration exploration missions (LDEMs) will differ tremendously from those currently available to crew medical officers (CMOs) on the International Space Station (ISS). Ground support will be more challenging due to distance-related communication delays and data transmission, and resource utilization must be optimized given limited ability for resupply. Clinical decision support systems (CDSSs) can help mitigate these limitations. The recent launch of generative artificial intelligence (AI) tools based upon large language models (LLM) support the creation of a smart assistant for onboard triage, diagnosis, and guided treatment of medical conditions during these missions. The Informing Mission Planning via Analysis of Complex Tradespaces (IMPACT) tool can help predict which clinical problems and outcomes are likely to occur for a design reference mission (DRM) and assist Medical Operations and systems engineering teams in creating a medical system that may optimally mitigate the predicted risks. The purpose of this study was to identify AI tools currently available or in development for the assistive diagnosis and care of medical conditions predicted for an extended duration Lunar mission. METHODS The 119 medical conditions currently built into the IMPACT suite were categorized into systems, and these diagnoses were used as keywords for our literature search. Using PubMed and Google Scholar, we performed a literature survey of AI tools applicable to these conditions. Article inclusion criteria included publication between the years 2017-2023, as the sentinel paper discussing the “selective attention” driving ChatGPT and other generative transformer models was published in June 2017. Where applicable, we reviewed only the top 1000 research articles (based on relevance) for each of the keywords/phrases. AI tools whose training sets were exclusive to a pediatric patient population were excluded. We also excluded any medical diagnostic tools (such as CT, MRI, mass spectrometry) or procedures (such as endoscopy, surgery) that are unlikely to be available during LDEMs due to mass and volume constraints, CMO knowledge, skills, and abilities, and/or inherent procedural risks. RESULTS Our survey highlighted several AI-driven tools for the triage, diagnosis, and management of those medical conditions highlighted by IMPACT. Selected publications for each medical condition were then screened for inclusion within ten systems-based categories including: general diagnostic tools (25), tools to diagnose and manage respiratory (40), dermatologic (34), neurologic (28), auditory and vestibular (30), ophthalmic (34), musculoskeletal (104), infection-associated (92), and gynecologic (19) conditions, as well as tools that could be deployed in the setting of trauma and emergency (34). CONCLUSIONS Numerous AI-driven tools were highlighted within this literature survey, ranging from chatbot assistants that triage knee pain to vision transformer models for diagnosis of ophthalmic conditions using ocular surface images captured with a mobile phone. Remaining challenges include optimizing connectivity and integration of existing and developing systems into the vehicles or habitats. Notably, findings from this survey could help guide the initial design of an all-encompassing, onboard medical AI assistant for use during future LDEMs.

R A Lacinski↗

Transformative Technology for FLASH Radiation Therapy: A Snowmass 2021 White Paper

Conventional cancer therapies include surgery, radiation therapy, chemotherapy, and, more recently, immunotherapy. These modalities are often combined to improve the therapeutic index. The general concept of radiation therapy is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and high radiation beams that deliver radiation dose with high conformality, e.g., protons and ions. However, treatment and cure are still limited by normal tissue radiation toxicity, with many patients experiencing acute and long-term side effects. Recently, however, a fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. The dose delivery conditions are not yet fully characterized. Still, it is currently estimated that large doses of 10 Gy or more delivered in 200 ms or less produce normal tissue sparing effects yet effectively kill tumor cells. There is a great opportunity, but also many technical challenges, for the accelerator community to create the required dose rates with novel and compact accelerators to ensure the safe delivery of FLASH radiation beams.

43 PARTICLE ACCELERATORS↗

Streptococcus pneumoniae HtrA is a dynamic and monomeric virulence factor capable of forming larger oligomeric complexes

Abstract High‐temperature requirement A (HtrA) proteases are a conserved family of serine proteases central to protein quality control and bacterial virulence. While Gram‐negative and human HtrAs are structurally well studied, Gram‐positive homologs remain essentially uncharacterized. Here, we present the first integrated structural and mechanistic analysis of a Gram‐positive HtrA, from Streptococcus pneumoniae , a virulence factor essential for adhesion and infection in vivo. Proteomic profiling of an htrA knockout and cleavage assays demonstrate that S. pneumoniae HtrA is required for protein quality control, with the PDZ domain mediating substrate recognition. Biochemically, S. pneumoniae HtrA exists exclusively as a monomer in solution, a striking divergence from canonical trimeric HtrAs that we show is shared with other Gram‐positive homologs. NMR analyses reveal that the monomer dynamically samples open and closed conformations, while cryo‐EM of a catalytic mutant identifies a hexamer stabilized by a unique LoopA–PDZ interaction. Together, these findings define S. pneumoniae HtrA as a dynamic monomer with interdomain coupling between its protease and PDZ domains, establishing Gram‐positive HtrAs as a mechanistically divergent subgroup within the HtrA family.

Lee, Eunjeong [Department of Biochemistry and Mole↗

The use of teledentistry in facilitating oral health for older adults: A scoping review

Teledentistry is used in many countries to provide oral health care services. However, using teledentistry to provide oral health care services for older adults is not well documented. This knowledge gap needs to be addressed, especially when accessing a dental clinic is not possible and teledentistry might be the only way for many older adults to receive oral health care services. Nine databases were searched and 3,396 studies were screened using established eligibility criteria. Included studies were original research or review articles in which the intervention of interest was delivered to an older adult population (≥ 60 years) via teledentistry. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review criteria. Nineteen studies were identified that met the criteria for inclusion. Only 1 study was from the United States. Seven studies had results focusing on older adult participants only, with most of those conducted in elder care facilities. The remainder consisted of studies with mixed-age populations reporting distinct results or information for older adults. The included studies used teledentistry, in both synchronous and asynchronous modes, to provide services such as diagnosis, oral hygiene promotion, assessment and referral of oral emergencies, and postintervention follow-up. Teledentistry comprises a variety of promising apps. Lastly, the authors identified and described uses, promising possibilities, and limitations of teledentistry to improve the oral health of older adults.

60 APPLIED LIFE SCIENCES↗

Intramedullary Unicortical Button and All-Suture Anchors Provide Similar Maximum Strength for Onlay Distal Biceps Tendon Repair

To evaluate the biomechanical profile of onlay distal biceps repair with an intramedullary unicortical button versus all-suture anchors under cyclic loading and maximal load to failure. Twenty paired fresh-frozen human cadaveric elbows were randomized to onlay distal biceps repair with either a single intramedullary button or with two 1.35-mm all-suture anchors. A 1.3-mm high tensile strength tape was used in a Krackow stitch to suture the tendons in both groups. Specimens and repair constructs were loaded for 3,000 cycles and then loaded to failure. Maximum load to failure, mode of failure, and construct elongation were recorded. Mean (± standard deviation) maximum load to failure for the unicortical intramedullary button and all-suture anchor repairs were 503.23 ± 141.77 N and 537.33 ± 262.13 N (P = .696), respectively. Mean maximum displacement after 3,000 cycles (± standard deviation) was 4.17 ± 2.05 mm in the button group and 2.06 ± 1.05 mm in the suture anchor group (P = .014). Mode of failure in the button group was suture tape rupture in 7 specimens, failure at the tendon–suture interface in 2 specimens, and button pullout in 1 specimen. Anchor pullout was the mode of failure in all suture anchor specimens. There were no tendon ruptures or radial tuberosity fractures in either group. In conclusion, this study demonstrates that onlay distal biceps repair with 2 all-suture anchors has similar maximum strength to repair with an intramedullary button and that both are viable options for fixation.

60 APPLIED LIFE SCIENCES↗

Cautious SBRT

No abstract prepared.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

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↗

A Phase 1 Dose Escalation Study of Neoadjuvant SBRT Plus Elective Nodal Radiation with Concurrent Capecitabine for Resectable Pancreatic Cancer

The role of neoadjuvant radiation for resectable pancreatic adenocarcinoma is controversial. We performed a prospective dose-escalation study of neoadjuvant stereotactic body radiation therapy (SBRT) with concurrent capecitabine and elective nodal irradiation (ENI) followed by surgical resection to explore the toxicity and feasibility of this approach.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

10-Year Breast Cancer Outcomes in Women ≤35 Years of Age

Breast cancer diagnosis at a very young age has been independently correlated with worse outcomes. Appropriately intensifying treatment in these patients is warranted, even as we acknowledge the risks of potentially mutagenic adjuvant therapies. We examined local control, distant control, overall survival, and secondary malignancy rates by age cohort and by initial surgical strategy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

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↗