The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

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 space1-6. 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 Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, 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.

Effects of an Oscillating Electric Field on and Dipole Moment Measurement of a Single Molecular Ion.

We characterize and model the Stark effect due to the radio-frequency (rf) electric field experienced by a molecular ion in an rf Paul trap, a leading systematic in the uncertainty of the field-free rotational transition. The ion is deliberately displaced to sample different known rf electric fields and measure the resultant shifts in transition frequencies. With this method, we determine the permanent electric dipole moment of CaH^{+}, and find close agreement with theory. The characterization is performed by using a frequency comb which probes rotational transitions in the molecular ion. With improved coherence of the comb laser, a fractional statistical uncertainty for a transition line center of as low as 4.6×10^{-13} was achieved.

Metabolomics as a Truly Translational Tool for Precision Medicine.

Metabolomics is unique among omics technologies in being applicable to metabolism and toxicity studies broadly across organisms (e.g., humans, other mammals, model organisms, and even bacteria) and across biological materials (e.g., blood, urine, saliva, biopsy, and stool), including cultured cells and subcellular fractions. Metabolomics can be used to characterize biologic response patterns in humans as well as to support mechanistic studies in model systems and ex vivo studies. A broad range of resources are available, including publicly accessible data repositories (e.g., Metabolomics Workbench), tools for biostatistics and bioinformatics (e.g., MetaboAnalyst), metabolite identification (e.g., Metlin), and pathway analysis (e.g., Kyoto Encyclopedia of Genes and Genomes). Thus, metabolomics is more than a promise of the future; metabolomics is already available as a translational approach to facilitate precision medicine. This ACT Symposium review will contain an introduction to metabolomics in toxicity studies followed by sections on translational metabolic networks, translational metabolite biomarkers of acetaminophen-induced acute liver injury, translational framework using high-resolution metabolomics for integrated pharmacokinetics and pharmacodynamics, and precision medicine applications: extracting actionable targets from untargeted metabolomics data following one year in space.

Mass-selective removal of ions from Paul traps using parametric excitation.

We study a method for mass-selective removal of ions from a Paul trap by parametric excitation. This can be achieved by applying an oscillating electric quadrupole field at twice the secular frequency ω sec using pairs of opposing electrodes. While excitation near the resonance with the secular frequency ω sec only leads to a linear increase of the amplitude with excitation duration, parametric excitation near 2 ω sec results in an exponential increase of the amplitude. This enables efficient removal of ions from the trap with modest excitation voltages and narrow bandwidth, therefore, substantially reducing the disturbance of ions with other charge-to-mass ratios. We numerically study and compare the mass selectivity of the two methods. In addition, we experimentally show that the barium isotopes with 136 and 137 nucleons can be removed from small ion crystals and ejected out of the trap while keeping 138 Ba + ions Doppler cooled, corresponding to a mass selectivity of better than Δ m / m = 1 / 138 . This method can be widely applied to ion trapping experiments without major modifications since it only requires modulating the potential of the ion trap.

DNA Transposons Favor De Novo Transcript Emergence Through Enrichment of Transcription Factor Binding Motifs.

De novo genes emerge from noncoding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading frame (ORF). Although the mechanisms underlying ORF emergence are well documented, relatively little is known about the mechanisms enabling new transcription events. Yet, in many species a continuum between absent and very prominent transcription has been reported for essentially all regions of the genome. In this study, we searched for de novo transcripts by using newly assembled genomes and transcriptomes of seven inbred lines of Drosophila melanogaster, originating from six European and one African population. This setup allowed us to detect sample specific de novo transcripts, and compare them to their homologous nontranscribed regions in other samples, as well as genic and intergenic control sequences. We studied the association with transposable elements (TEs) and the enrichment of transcription factor motifs upstream of de novo emerged transcripts and compared them with regulatory elements. We found that de novo transcripts overlap with TEs more often than expected by chance. The emergence of new transcripts correlates with regions of high guanine-cytosine content and TE expression. Moreover, upstream regions of de novo transcripts are highly enriched with regulatory motifs. Such motifs are more enriched in new transcripts overlapping with TEs, particularly DNA TEs, and are more conserved upstream de novo transcripts than upstream their 'nontranscribed homologs'. Overall, our study demonstrates that TE insertion is important for transcript emergence, partly by introducing new regulatory motifs from DNA TE families.

Quantum state tracking and control of a single molecular ion in a thermal environment.

Understanding molecular state evolution is central to many disciplines, including molecular dynamics, precision measurement, and molecule-based quantum technology. Details of this evolution are obscured when observing a statistical ensemble of molecules. Here, we report real-time observations of thermal radiation-driven transitions between individual states ("jumps") of a single molecule. We reversed these jumps through microwave-driven transitions, which resulted in a 20-fold improvement in the time the molecule dwells in a chosen state. The measured transition rates showed anisotropy in the thermal environment, pointing to the possibility of using single molecules as in situ probes for the strengths of ambient fields. Our approaches for state detection and manipulation could apply to a wide range of species, facilitating their uses in fields including quantum science, molecular physics, and ion-neutral chemistry.

Kavalactones support motivation to move during intensive training in males preparing for military special operations forces.

BACKGROUND: Military special operators, elite athletes, and others requiring uninterrupted optimal performance currently lack options for sleep and mood support without performance-inhibiting effects. Kavalactones, derived from the root of the kava plant (Piper methysticum Forst), have been shown to elevate mood and wellbeing by producing a feeling of relaxation without addiction or cognitive impairment. METHODS: In this placebo-controlled, crossover study (NCT05381025), we investigated the effects of 2 weeks of kavalactones use on cortisol (diurnal salivary), sleep (RSQ-W; Restorative Sleep Questionnaire, Weekly), mood (DASS-21; Depression Anxiety Stress Scale-21), and motivation state to expend (Move) or conserve (Rest) energy (CRAVE; Cravings for Rest and Volitional Energy Expenditure, Right Now) in a cohort of 15 healthy, physically fit young males engaged in a rigorous, two-a-day preparation class for special operations forces qualification. RESULTS: Cortisol, sleep, and mood were within normal, healthy parameters in this cohort at baseline. This remained unchanged with kavalactones use with no significant findings of clinical interest. However, a statistically similar, positive slope for within-group Move scores was seen in both groups during kavalactones loading (first group Move slope 2.25, second group Move slope 3.29, p = 0.299). This trend was seen regardless of order and with no apparent effects on the Rest metric (all p ≥ 0.05). Moreover, a significant between-group difference appeared after 1 week of kavalactones use in the first phase (p = 0.044) and persisted through the end of the first loading period (p = 0.022). Following the 10-day washout, this between-groups divergence remained significant (p = 0.038) but was reversed by 1 week after the crossover (p = 0.072), with Move scores once again statistically similar between groups and compared to baseline at study end. Furthermore, the group taking kavalactones first never experienced a significant decrease in Move motivation state (lowest mean score 21.0, highest 28.6, all p ≥ 0.05), while the group receiving kavalactones in the last 2 weeks of the study had Move scores that were statistically lower than baseline (lowest mean score 8.6, highest 25.9, all p ≤ 0.05) at all time points but the last (p = 0.063) after 2 weeks of kavalactones exposure. CONCLUSIONS: We report a novel finding that kavalactones may support performance by maintaining or rescuing the desire to expend energy in the context of significant physical and mental strain in well-conditioned individuals, even in a context of already normal cortisol, sleep, and mood.

A systematic pan-cancer study on deep learning-based prediction of multi-omic biomarkers from routine pathology images.

BACKGROUND: The objective of this comprehensive pan-cancer study is to evaluate the potential of deep learning (DL) for molecular profiling of multi-omic biomarkers directly from hematoxylin and eosin (H&E)-stained whole slide images. METHODS: A total of 12,093 DL models predicting 4031 multi-omic biomarkers across 32 cancer types were trained and validated. The study included a broad range of genetic, transcriptomic, and proteomic biomarkers, as well as established prognostic markers, molecular subtypes, and clinical outcomes. RESULTS: Here we show that 50% of the models achieve an area under the curve (AUC) of 0.644 or higher. The observed AUC for 25% of the models is at least 0.719 and exceeds 0.834 for the top 5%. Molecular profiling with image-based histomorphological features is generally considered feasible for most of the investigated biomarkers and across different cancer types. The performance appears to be independent of tumor purity, sample size, and class ratio (prevalence), suggesting a degree of inherent predictability in histomorphology. CONCLUSIONS: The results demonstrate that DL holds promise to predict a wide range of biomarkers across the omics spectrum using only H&E-stained histological slides of solid tumors. This paves the way for accelerating diagnosis and developing more precise treatments for cancer patients.

Molecular profiling tests are used to check cancers for changes in certain genes, proteins, or other molecules. Results of such tests can be used to identify the most effective treatment for cancer patients. Faster and more accessible alternatives to standard tests are needed to improve cancer care. This study investigates whether deep learning (DL), a series of advanced computer techniques, can perform molecular profiling directly from routinely-collected images of tumor specimens used for diagnostic purposes. Over 12,000 DL models were utilized to evaluate thousands of biomarkers using statistical approaches. The results indicate that DL can effectively detect molecular changes in a tumor from these images, for many biomarkers and tumor types. The study shows that DL-based molecular profiling from images is possible. Introducing this type of approach into routine clinical workflows could potentially accelerate treatment decisions and improve outcomes.

A Multiomics, Molecular Atlas of Breast Cancer Survivors.

Breast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.

Collection of biospecimens from the inspiration4 mission establishes the standards for the space omics and medical atlas (SOMA).

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments.

Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.

Background: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure. Methods: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden. Result: Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight. Conclusion: Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.

Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight.

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Collection of Biospecimens from the Inspiration4 Mission Establishes the Standards for the Space Omics and Medical Atlas (SOMA).

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from the crew at different stages of the mission, including before (L-92, L-44, L-3 days), during (FD1, FD2, FD3), and after (R+1, R+45, R+82, R+194 days) spaceflight, creating a longitudinal sample set. The collection process included samples such as venous blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies, which were processed to obtain aliquots of serum, plasma, extracellular vesicles, and peripheral blood mononuclear cells. All samples were then processed in clinical and research laboratories for optimal isolation and testing of DNA, RNA, proteins, metabolites, and other biomolecules. This paper describes the complete set of collected biospecimens, their processing steps, and long-term biobanking methods, which enable future molecular assays and testing. As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can also aid future experiments in human spaceflight and space biology.

Recovery From Eccentric Squat Exercise in Resistance-Trained Young and Master Athletes With Similar Maximum Strength: Combining Cold Water Immersion and Compression.

The aim of this study was to investigate whether recovery from eccentric squat exercise varies depending on age and to assess whether the use of a mixed-method recovery (MMR) consisting of cold water immersion and compression tights benefits recovery. Sixteen healthy and resistance-trained young (age, 22.1±2.1years; N=8) and master male athletes (age, 52.4±3.5years; N=8), who had a similar half squat 1-repetition maximum relative to body weight, completed two identical squat exercise training sessions, separated by a 2-week washout period. Training sessions were followed by either MMR or passive recovery (PR). Internal training loads [heart rate and blood lactate concentration (BLa)] were recorded during and after squat sessions. Furthermore, maximal voluntary isometric contraction (MVIC) force, countermovement jump (CMJ) height, resting twitch force of the knee extensors, serum concentration of creatine kinase (CK), muscle soreness (MS), and perceived physical performance capability (PPC) were determined before and after training as well as after 24, 48, and 72h of recovery. A three-way mixed ANOVA revealed a significant time effect of the squat protocol on markers of fatigue and recovery (p<0.05; decreased MVIC, CMJ, twitch force, and PPC; increased CK and MS). Age-related differences were found for BLa, MS, and PPC (higher post-exercise fatigue in younger athletes). A significant two-way interaction between recovery strategy and time of measurement was found for MS and PPC (p<0.05; faster recovery after MMR). In three participants (two young and one master athlete), the individual results revealed a consistently positive response to MMR. In conclusion, master athletes neither reach higher fatigue levels nor recover more slowly than the younger athletes. Furthermore, the results indicate that MMR after resistance exercise does not contribute to a faster recovery of physical performance, neuromuscular function, or muscle damage, but promotes recovery of perceptual measures regardless of age.

Simulation of stationary Gaussian noise with regard to the Langevin equation with memory effect.

We present an efficient method for simulating a stationary Gaussian noise with an arbitrary covariance function, and then we study numerically the impact of time-correlated noise on the time evolution of a (1+1)-dimensional generalized Langevin equation by comparing also to analytical results. Finally, we apply our method to the generalized Langevin equation with an external harmonic and double-well potential.

A far-off-resonance optical trap for a Ba+ ion.

Optical trapping and ions combine unique advantages of independently striving fields of research. Light fields can form versatile potential landscapes, such as optical lattices, for neutral and charged atoms, while avoiding detrimental implications of established radiofrequency traps. Ions interact via long-range Coulomb forces and permit control and detection of their motional and electronic states on the quantum level. Here we show optical trapping of (138)Ba(+) ions in the absence of radio-frequency fields via a far-detuned dipole trap, suppressing photon scattering by three orders of magnitude and the related recoil heating by four orders of magnitude. To enhance the prospects for optical as well as hybrid traps, we demonstrate a method for stray electric field compensation to a level below 9 mV m(-1). Our results will be relevant, for example, for ion-atom ensembles, to enable 4-5 orders of magnitude lower common temperatures, accessing the regime of ultracold interaction and chemistry, where quantum effects are predicted to dominate.