While AI holds the potential to revolutionize space life sciences, realizing this promise is contingent upon the systematic restructuring of heterogeneous spaceflight biological data into machine-actionable, AI-ready forms. Even though open access principles support human reuse and scientific reproducibility, this does not necessarily enable AI systems to access and analyze such a diverse set of scientific datasets. In addition, the growing array of AI approaches places distinct demands on data structure, metadata, and access interfaces. In order to respond to such growing changes we propose a three-tier approach, proceeding from FAIR to AI-ready to space-ready data. We discuss existing infrastructures and how they can be improved to close the AI access gap. We conclude by proposing a neutral international coordinating body as the governance backbone for the trustworthy, agent-accessible space biology infrastructure that deep space biological research will require.

Abstract Spaceflight is a stochastic risk factor for development of cancer in astronauts and experimental data beyond low earth orbit is scarce1. Our understanding of role of tumorigenic pathways in the context of space biology is limited. We compared differentially expressed genes (DEGs), signaling pathways, and cancer hallmarks between human tumor tissue with Spaceflight data from civilian astronauts on private missions and rodents on Space missions2.Astronaut RNA Seq data from the Inspiration4 (I4) mission and NASA Twin study were used conjointly with data from space-flown rodents and compared to transcriptome from organ-matched human tumor counterparts from NCI Genomic Data Commons. The peripheral blood transcriptome of the I4 crew revealed a temporal trend of oncogenic gene dysregulation from pre-flight to 82 days after return to Earth (R+82). Early post-flight window showed activation of pro-tumorigenic and immune-mediated genes namely KRAS, MTOR, STAT3, RARA, and PIK3CA on R+1 (immediate post-spaceflight), of which sustained activation of key genes were observed on R+45 (45 days post return to Earth) and on R+82. DNA damage repair genes such as MRE11, ATR, ABL1, RAD51B, RAD51D, FANCA, and CREBBP were activated in parallel. Over time, most regulatory genes recovered, but therapeutic targets namely ALK, ROS1, NTRK3, POLE, RAD51D, MTAP, ESR1, FGFR3, TSC1, STK11, ABL1, CREBBP, RAF1, NRG1, BCL6, and KMT2D were found to be upregulated post-flight after readjusting to Earth, irrespective of inter-individual variability. Sustained upregulation of stemness factors STAT3 and FOXP1 indicate adaptivity or immune system tuning post-stress but warrants attention for long term studies for potential oncogenic risks.In parallel, multi-organ sorted patient and rodent data offered staggering insights into tumorigenic roles of major signaling cascades in cancer. Significant overlaps in DEGs were observed between primary human tumors and spaceflown models notably in Breast (p 4.84E-57, OR 7.7), Colon (p 9.24E-46, OR 25), Kidney (p 9.21E-62, OR 9.3), Lung (p 1.38E-51, OR 28), and Skin (p1.23E-85, OR 119). GSEA analysis revealed pro-tumorigenic pathway enrichment. For example, in breast, we observed activation in pathways of MYC targets (NES 2.17, FDRq 0.003), mTORC (NES 2.42, FDRq 0.000), PI3K pathway (NES 1.31, FDRq 0.123), DNA damage repair (NES 1.76, FDRq 0.002), Oxidative Phosphorylation (NES 3.28, FDRq 0.000), and ROS cascades (NES 2.10, FDRq 0.000).The distinction between signaling pathway dysregulations in healthy tissue, benign tumors, stress-induced tissue, and florid malignancy remains a question. Sustained activation of pathways post-spaceflight in astronauts is a crucial finding that mirrors a cellular environment observed in human pre-malignant tissues. Simultaneously, the significant similarity in cellular pathways between tumors and spaceflight petitions cognizance of the bivalent nature of pathways in cancer3. Citation Format: Anu R I, Josef Borg, JangKeun Kim, Tricia Larose, Ryan T. Scott, Joseph Borg, Christopher E. Mason, Afshin Beheshti, Kurt van der Speeten. Signaling pathway insights into spaceflight cancer risks [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5273.

Spaceflight-associated neuro-ocular syndrome (SANS) poses significant ocular health risks in long-duration missions, yet its molecular mechanisms remain incompletely understood. Oxidative stress and apoptosis are candidate drivers, but their transcriptomic-phenotypic relationships in spaceflight-exposed retinal tissue have not been systematically characterized. We applied a machine learning ensemble to predict two ocular phenotypes: 4-hydroxynonenal (4-HNE) endothelial cell density as a marker of oxidative damage, and TUNEL endothelial cell density as a marker of apoptosis. In this observational study, we use transcriptomic data from a controlled experiment with ground control and spaceflown mice to predict these phenotypes. Gene Ontology pathway enrichment was performed using the most predictive genes for each phenotype. Genes predicting 4-HNE converge on membrane-associated pathways, photoreceptor modification, synaptic dysfunction, and extracellular matrix dysregulation, including B2m, Trf, Cnga1, mt-Nd1, Snap25, and Efemp1. Genes predicting TUNEL emphasize stress-induced apoptosis, rod photoreceptor degeneration, and endoplasmic reticulum dysfunction, with Ddit4, Nrl, Rom1, Reep6, and Gabarapl1 emerging as central regulators. Oxidative lipid peroxidation and apoptotic cell death represent complementary and molecularly distinct pathological mechanisms in spaceflight-exposed murine retinal tissue. The gene signatures provide a putative molecular framework for developing noninvasive biomarkers and therapeutic targets to monitor and protect astronaut visual health during long-duration and deep-space missions.

The NASA Rodent Habitat aboard the International Space Station enabled long-duration studies of behavioral responses to spaceflight, but video-based behavioral analysis has relied on laborious manual annotation. No study has tested whether deep learning tools can automate this analysis under the demanding imaging conditions of orbital vivaria. We applied pose estimation (SLEAP) and behavioral segmentation (DeepEthogram) to archival footage from the Rodent Research-1 mission. Nine labelers annotated 3,249 pose labels across 2,063 frames, and three behaviorists labeled 411,194 frames across 66 videos. Pose tracking accuracy approximated human inter-annotator variability despite progressive lens soiling, grid occlusions, and spherical aberration. Behavioral classification across eight categories achieved accuracy of 0.86-0.90 and suggests progressive behavioral adaptations to microgravity. Kinematic reconstruction of circling estimated centripetal accelerations periodically approaching 1g. This is the first application of deep learning-based pose estimation and behavioral segmentation to rodents in spaceflight, establishing benchmarks for future monitoring systems.

This systematic review aimed to characterize the landscape of cardiovascular research in the context of spaceflight and its Earth-based analogs. In collaboration with subject matter experts from the Ames Life Science Data Archive Analysis Working Group, we developed targeted search terms for spaceflight-related exposures and specific cardiovascular outcomes. A team of librarians translated these terms into structured search strategies across Ovid Medline, Embase, and CINAHL, yielding 18,837 records after deduplication. Screening was completed in collaboration with citizen scientists from the Space Open Life Sciences Team for International Collaborative Exploration (SOLSTICE). Title and abstract screening identified 3512 relevant articles. Articles were labelled based on population (human, rodent, primate, other), exposure type (actual spaceflight, simulated microgravity, other), and primary outcome focus (cardiovascular, hematopoietic, or other). Humans comprised 69.1% of the study populations. Actual spaceflight was studied in 28.1% of articles, and Earth-based models of microgravity were used in 43.3%. Cardiovascular outcomes were the most frequently reported (60.1%). For full-text screening, the primary focus was on 855 studies reporting cardiovascular outcomes in humans exposed to actual microgravity. Within this group, the most common outcomes were heart rate (70 studies), cardiac measurements (47 studies), and blood pressure (45 studies), while vasculature outcomes were reported in 27 studies. This curated and annotated dataset provides a foundation for future quantitative synthesis to support the mechanistic understanding of spaceflight-induced cardiovascular changes. The findings are directly relevant to upcoming human missions to the Moon and Mars, helping inform health risk mitigation strategies for long-duration space travel.

Space flight exposes astronauts to stressors that alter the immune response, rendering them vulnerable to infections and diseases. In this study, we aimed to determine the levels of inflammasome activation in the brains of mice that were housed in the International Space Station (ISS) for 37 days. C57BL/6 mice were launched to the ISS as part of NASA’s Rodent Research 1 Mission on SpaceX-4 CRS-4 Dragon cargo spacecraft from 21 September 2014 to 25 October 2014. Dissected mouse brains from that mission were analyzed by immunoblotting of inflammasome signaling proteins and Electrochemiluminescence Immunoassay (ECLIA) for inflammatory cytokine levels. Our data indicate decreased inflammasome activation in the brains of mice that were housed in the ISS for 37 days when compared to the brains of mice that were maintained on the ground, and in mice corresponding to the baseline group that were sacrificed at the time of launching of SpaceX-4. Moreover, we did not detect any significant changes in the expression levels of the pro-inflammatory cytokines TNF-α, IL-2, IFN-γ, IL-5, IL-6, IL-12p70 and IL-10 between the ground control and the flight groups. Together, these studies suggest that spaceflight results in a decrease in the levels of innate immune signaling molecules that govern inflammasome signaling in the brain of mice.

The public and commercial space industries are planning longer duration and more distant space missions, including the establishment of a habitable lunar base and crewed missions to Mars. These missions will generate large volumes of data too large and expensive to send back to Earth, some of which may be subject to privacy protections. To support Earth-independent scientific and medical operations, such missions can leverage artificial intelligence and machine learning to build models to assist with science experiments, crew healthcare, resource management, spacecraft maintenance, scheduling, and other critical tasks. However, transmitting large volumes of data between Earth and space for model development consumes valuable bandwidth, is vulnerable to communication disruptions, and may compromise crew safety and data privacy. Federated learning provides a solution by enabling model training without transferring large, potentially privacy-sensitive datasets between Earth and space. In this work, we present a foundational architecture that facilitates the secure transmission of model updates between Earth and the International Space Station. This architecture represents the first federated learning framework deployed in a spaceflight setting, enabling classifier models to be trained and updated between Earth and the ISS using both real biomedical research data and synthetically generated data. ### Competing Interest Statement The authors have declared no competing interest.

Spaceflight has several detrimental effects on human and rodent health. For example, liver dysfunction is a common phenotype observed in space-flown rodents, and this dysfunction is partially reflected in transcriptomic changes. Studies linking transcriptomics with liver dysfunction rely on tools which exploit correlation, but these tools make no attempt to disambiguate true correlations from spurious ones. In this work, we use a machine learning ensemble of causal inference methods called the Causal Research and Inference Search Platform (CRISP) which was developed to predict causal features of a binary response variable from high-dimensional input. We used CRISP to identify genes robustly correlated with a lipid density phenotype using transcriptomic and histological data from the NASA Open Science Data Repository (OSDR). Our approach identified genes and molecular targets not predicted by previous traditional differential gene expression analyses. These genes are likely to play a pivotal role in the liver dysfunction observed in space-flown rodents, and this work opens the door to identifying novel countermeasures for space travel.

Spaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space(1-6). Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study(7), JAXA CFE study(8,9), SpaceX Inspiration4 crew(10-12), Axiom and Polaris. The SOMA resource represents a more than tenfold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiome datasets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific mouse datasets. Leveraging the datasets, tools and resources in SOMA can help to accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation and countermeasure data for upcoming lunar, Mars and exploration-class missions.

In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female health, potentially increasing risks for future pregnancies upon return to Earth, particularly related to small-for-gestational-age (SGA) fetuses. To address this, we identify a shared microRNA (miRNA) signature between SGA and the space environment, conserved across humans and mice. These miRNAs target genes and pathways relevant to diseases and development. Employing a machine learning approach, we identify potential FDA-approved drugs to mitigate these risks, including estrogen and progesterone receptor antagonists, vitamin D receptor antagonists, and DNA polymerase inhibitors. This study underscores potential pregnancy-related health risks for female astronauts and proposes pharmaceutical interventions to counteract the impact of space travel on female health.

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.

The modified Broström procedure is widely accepted to address surgical treatment of chronic lateral ankle instability. Augmentation of the anterior talofibular ligament has become popular in an effort to improve outcomes over modified Broström alone. The purpose of this study was to evaluate outcomes of surgery using a modified Broström alone versus a modified Broström augmented with a synthetic polycaprolactone based-polyurethane urea matrix.

Space biology and health data are critical for the success of deep space missions and sustainable human presence off-world. At the core of effectively managing biomedical risks is the commitment to open science principles, which ensure that data are findable, accessible, interoperable, reusable, reproducible and maximally open. The 2021 integration of the Ames Life Sciences Data Archive with GeneLab to establish the NASA Open Science Data Repository significantly enhanced access to a wide range of life sciences, biomedical-clinical and mission telemetry data alongside existing 'omics data from GeneLab. This paper describes the new database, its architecture and new data streams supporting diverse data types and enhancing data submission, retrieval and analysis. Features include the biological data management environment for improved data submission, a new user interface, controlled data access, an enhanced API and comprehensive public visualization tools for environmental telemetry, radiation dosimetry data and 'omics analyses. By fostering global collaboration through its analysis working groups and training programs, the open science data repository promotes widespread engagement in space biology, ensuring transparency and inclusivity in research. It supports the global scientific community in advancing our understanding of spaceflight's impact on biological systems, ensuring humans will thrive in future deep space missions. [GRAPHICS]

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However, for scientists wishing to publish obtained images and image-analysis results, there are currently no unified guidelines for best practices. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here, we present community-developed checklists for preparing light microscopy images and describing image analyses for publications. These checklists offer authors, readers and publishers key recommendations for image formatting and annotation, color selection, data availability and reporting image-analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby to heighten the quality and explanatory power of microscopy data. Community-developed checklists offer best-practice guidance for biologists preparing light microscopy images and describing image analyses for publications.

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts’ increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR.

As the space industry grows exponentially and aspirations for space travel expand, we are entering a new era where we will very likely become an interplanetary species. Although reproduction is an essential human function and necessary for species survival, we have remarkably little knowledge regarding the impact of space travel on the female reproductive system. The effects of spaceflight on human reproductive potential, fertility, implantation and subsequent pregnancy resulting in a healthy live birth must be considered before planning prolonged spaceflight missions and the colonization of planets. In this review, we explore what is known and what remains to be learned about the effects of space travel on female reproductive endocrinology. We also delve deeper into reproductive endocrinology and discuss normal physiologic mechanisms at the molecular level to have a better understanding of how it may change during spaceflight. The rigors of spaceflight including radiation, gravitational stressors, and circadian rhythm changes could potentially affect ovulation, fertilization, endometrial receptivity, preimplantation embryo development, embryo implantation, placentation, and pregnancy. Thus, we will examine what is known about spaceflight effects on the hypothalamic–pituitary–gonadal (HPG) axis, ovarian folliculogenesis and steroidogenesis, early embryogenesis, endometrial receptivity, and pregnancy. We further discuss the recent advances in reproductive endocrinology and future research platforms. Establishing a better understanding of the effect of space travel on female reproductive health, as well as developing countermeasures to mitigate adverse effects, are decisive components of our species’ successful transition to an interplanetary one.

Objectives: Hemorrhage in osteoporotic pelvic ring fractures is a rare, but serious complication. Most bleeding comes from the bone or venous plexuses, but arterial injury does occur. The purpose of this study was to characterize a large geriatric pelvic fracture cohort and determine the prevalence of pelvic CT angiography (CTA) and subsequent need for arterial embolization. Methods: A cohort of geriatric pelvic fracture patients at two level 1 trauma centers was reviewed. Many epidemiologic and patient factors were collected for cohort characterization. The primary outcome was if patients underwent a CTA of the pelvis and subsequently underwent arterial embolization. Results: There were 457 patients included and mean age was 83.1 years (range 65-100). Most patients had a low energy mechanism (91.4 %). In-hospital mortality was recorded for 30 cases (6.6 %). Of these deaths, two received a pelvic CTA and two had an embolization procedure. Pelvic CTA was performed on 33 patients (7.2 %). Fourteen patients (3.0 %) had an arterial embolization procedure. A high energy mechanism of injury was associated with receiving a pelvic CTA (p p = 0.0067). Mechanism of injury was not associated with undergoing an embolization procedure (p p = 0.685). Discussion: In the geriatric population, even patients with stable pelvic fractures can present with life-threatening arterial bleeding. A non-insignificant percentage of patients will require CTA for suspected bleeding (7.2 %) and embolization to treat confirmed arterial bleeding (3.0 %). Conclusions: Bleeding events in geriatric pelvic ring injuries is a previously under researched area of orthopedic trauma. Further research is needed to elucidate the exact pathomechanisms of arterial injury and what patients or injury patterns are most significantly associated. Specifically, larger cohort sizes and evaluating our existing cohort with different injury classification systems may yield useful results.

INTRODUCTION:The purpose of this study was to evaluate surgeons' ability to perform or supervise a standard operation with agreed-upon radiologic parameters after being on call. METHODS:We reviewed a consecutive series of patients with intertrochanteric hip fractures treated with a fixed angle device at 9 centers and compared corrected tip-apex distance and reduction quality for post-call surgeons versus those who were not. Subgroup analyses included surgeons who operated the night before versus not and attending-only versus resident involved cases. Secondary outcomes included union and perioperative complications. RESULTS:One thousand seven hundred fourteen patients were of average age 77 years. Post-call surgeons treated 823 patients and control surgeons treated 891. Surgical corrected tip-apex distance did not differ between groups: on-call 18 mm versus control 18 mm (P = 0.59). The Garden indices were 160° on the AP and 179° on the lateral in both groups. In 66 cases performed by surgeons who operated the night before, the TAD was 17 mm. No difference was noted in corrected tip-apex distance with and without resident involvement (P = 0.101). No difference was observed in pooled fracture-related complications (P = 0.23). CONCLUSION:Post-call surgeons demonstrated no difference in quality and no increase in complications when performing hip fracture repair the next day compared with surgeons who were not on call.

The spaceflight environment affects the structure and function of the cardiovascular system, including fluid redistribution, alterations in blood pressure, and changes in cardiac output. The goal of this project is to quantitatively synthesize the data on the effects of actual or simulated microgravity on the cardiovascular system. In collaboration with the Ames Life Science Data Archive (ALSDA) Analysis Working Group we developed a list of relevant cardiovascular search terms, based on which medical librarians generated the search strategy in Medline, CINAHL, Embase, and NASA repositories, yielding 18,837 articles. In parallel, we recruited similar to 100 young professionals through space industry-affiliated organizations. These individuals completed a virtual training course on the nature and methodologies of the project. They initially screened at a rate of 5,000 articles/month; however, individualized training from project supervisors increased this rate to 60,000 articles/month. Following title/abstract screening, 3,539 included articles were labelled and grouped according to population (human, rodent) and experimental methods (simulated microgravity, actual spaceflight) for full-text screening. Full-text screening of similar to 900 articles in a humans and actual microgravity subgroup is currently underway, with 200 articles now completed. We anticipate that teams will be extracting and curating and submitting data into the new ALSDA submission portal and repository. Our approach reduces the time to complete screening from years to several months, and will enrich publicly accessible datasets for reuse, modeling, and machine learning. Our project provides a unique, open-access educational experience to space research and training in knowledge synthesis tools.