Inspiration4 data access through the NASA Open Science Data Repository.

The increasing accessibility of commercial and private space travel necessitates a profound understanding of its impact on human health. The NASA Open Science Data Repository (OSDR) provides transparent and FAIR access to biological studies, notably the SpaceX Inspiration4 (I4) mission, which amassed extensive data from civilian astronauts. This dataset encompasses omics and clinical assays, facilitating comprehensive research on space-induced biological responses. These data allow for multi-modal, longitudinal assessments, bridging the gap between human and model organism studies. Crucially, community-driven data standards established by NASA's OSDR Analysis Working Groups empower artificial intelligence and machine learning to glean invaluable insights, guiding future mission planning and health risk mitigation. This article presents a concise guide to access and analyze I4 data in OSDR, including programmatic access through GLOpenAPI. This pioneering effort establishes a precedent for post-mission health monitoring programs within space agencies, propelling research in the burgeoning field of commercial space travel's impact on human physiology.

Community-developed checklists for publishing images and image analyses.

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.

Explainable machine learning identifies multi-omics signatures of muscle response to spaceflight in mice.

The adverse effects of microgravity exposure on mammalian physiology during spaceflight necessitate a deep understanding of the underlying mechanisms to develop effective countermeasures. One such concern is muscle atrophy, which is partly attributed to the dysregulation of calcium levels due to abnormalities in SERCA pump functioning. To identify potential biomarkers for this condition, multi-omics data and physiological data available on the NASA Open Science Data Repository (osdr.nasa.gov) were used, and machine learning methods were employed. Specifically, we used multi-omics (transcriptomic, proteomic, and DNA methylation) data and calcium reuptake data collected from C57BL/6 J mouse soleus and tibialis anterior tissues during several 30+ day-long missions on the international space station. The QLattice symbolic regression algorithm was introduced to generate highly explainable models that predict either experimental conditions or calcium reuptake levels based on multi-omics features. The list of candidate models established by QLattice was used to identify key features contributing to the predictive capability of these models, with Acyp1 and Rps7 proteins found to be the most predictive biomarkers related to the resilience of the tibialis anterior muscle in space. These findings could serve as targets for future interventions aiming to reduce the extent of muscle atrophy during space travel.

Viral activation and ecological restructuring characterize a microbiome axis of spaceflight-associated immune activation.

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes, which play a role in some space-derived health disorders. However, documenting the response of microbiota to spaceflight has been difficult thus far due to mission constraints that lead to limited sampling. Here, we executed a six-month longitudinal study centered on a three-day flight to quantify the high-resolution microbiome response to spaceflight. Via paired metagenomics and metatranscriptomics alongside single immune profiling, we resolved a microbiome "architecture" of spaceflight characterized by time-dependent and taxonomically divergent microbiome alterations across 750 samples and ten body sites. We observed pan-phyletic viral activation and signs of persistent changes that, in the oral microbiome, yielded plaque-associated pathobionts with strong associations to immune cell gene expression. Further, we found enrichments of microbial genes associated with antibiotic production, toxin-antitoxin systems, and stress response enriched universally across the body sites. We also used strain-level tracking to measure the potential propagation of microbial species from the crew members to each other and the environment, identifying microbes that were prone to seed the capsule surface and move between the crew. Finally, we identified associations between microbiome and host immune cell shifts, proposing both a microbiome axis of immune changes during flight as well as the sources of some of those changes. In summary, these datasets and methods reveal connections between crew immunology, the microbiome, and their likely drivers and lay the groundwork for future microbiome studies of spaceflight.

The Posttraumatic Tarsometatarsal Joints.

Tarsometatarsal joint injuries can be painful and debilitating and are most commonly due to direct or indirect trauma. Posttraumatic arthritis is a well-known long-term complication, with incidence as high as 58%. Conservative treatment options include shoe modifications, orthotic inserts, topical or oral anti-inflammatories, and intra-articular corticosteroid injections. There are various joint prep and fixation techniques reported in the literature, many with positive clinical and radiographic outcomes. This article discusses nonoperative and operative management of posttraumatic tarsometatarsal joint arthritis, reviews available literature, and includes the authors' tips and techniques.

A Comparison of Ankle Fractures Relative to Other Fragility Fractures: A Review and Analysis of the American Orthopaedic Association's Own the Bone Database.

BACKGROUND: Ankle fragility fractures (AFX) continue to increase in the elderly population. There is limited knowledge of AFX characteristics compared to nonankle fragility fractures (NAFX). The American Orthopaedic Association's Own the Bone (OTB) is a fragility fracture initiative. This robust data set was used to examine and compare characteristics of patients presenting with AFX to those with NAFX. METHODS: The OTB database contained 72,617 fragility fractures between January 2009 and March of 2022 and were reviewed in our secondary cohort comparative analysis. After exclusions, AFX accounted for 3229 patients and 54,772 patients were in the NAFX cohort. Bivariate analysis and logistic regression compared the AFX and NAFX groups concerning demographics, bone health factors, medication use, and prior fragility fracture. RESULTS: AFX patients were found to have a higher likelihood to be younger (67.6 years old), female (81.4%), non-Caucasian (11.7%) and have a higher BMI (30.6) compared to NAFX. Prior AFX predicted the risk of a future AFX. The probability of an AFX increased with increased age and BMI. CONCLUSION: A prior AFX is independently predictive of subsequent AFX. Therefore, these fractures should be considered a sentinel event. These patients are more likely to have higher BMI, to be of female gender, non-Caucasian race, and are younger compared to patients with NAFX. LEVEL OF EVIDENCE: Level III, retrospective cohort.

Management of Subchondral Lesions in the Foot and Ankle.

The treatment of subchondral lesions is an area with limited focus within the foot and ankle literature. The literature has shown an association between disruption of the subchondral bone plate and the formation of subchondral cysts. The primary causes of subchondral lesions are acute trauma, repetitive microtrauma, as well as idiopathic means. Evaluation of these injuries should be done carefully and often requires advanced imaging including MRI and computed tomography. Treatment does vary depending on the presentation of the subchondral lesion with or without the presence of an osteochondral lesion.

Community-developed checklists for publishing images and image analyses.

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 the obtained images and image analyses results, there are to date no unified guidelines. 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 image analysis for publications. These checklists offer authors, readers, and publishers key recommendations for image formatting and annotation, color selection, data availability, and for reporting image analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby heighten the quality and explanatory power of microscopy data is in publications.

Challenges and considerations for single-cell and spatially resolved transcriptomics sample collection during spaceflight.

Single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) have experienced rapid development in recent years. The findings of spaceflight-based scRNA-seq and SRT investigations are likely to improve our understanding of life in space and our comprehension of gene expression in various cell systems and tissue dynamics. However, compared to their Earth-based counterparts, gene expression experiments conducted in spaceflight have not experienced the same pace of development. Out of the hundreds of spaceflight gene expression datasets available, only a few used scRNA-seq and SRT. In this perspective piece, we explore the growing importance of scRNA-seq and SRT in space biology and discuss the challenges and considerations relevant to robust experimental design to enable growth of these methods in the field.

Validating Causal Diagrams of Human Health Risks for Spaceflight: An Example Using Bone Data from Rodents.

As part of the risk management plan for human system risks at the US National Aeronautics and Space Administration (NASA), the NASA Human Systems Risk Board uses causal diagrams (in the form of directed, acyclic graphs, or DAGs) to communicate the complex web of events that leads from exposure to the spaceflight environment to performance and health outcomes. However, the use of DAGs in this way is relatively new at NASA, and thus far, no method has been articulated for testing their veracity using empirical data. In this paper, we demonstrate a set of procedures for doing so, using (a) a DAG related to the risk of bone fracture after exposure to spaceflight; and (b) four datasets originally generated to investigate this phenomenon in rodents. Tests of expected marginal correlation and conditional independencies derived from the DAG indicate that the rodent data largely agree with the structure of the diagram. Incongruencies between tests and the expected relationships in one of the datasets are likely explained by inadequate representation of a key DAG variable in the dataset. Future directions include greater tie-in with human data sources, including multiomics data, which may allow for more robust characterization and measurement of DAG variables.

Soft Tissue Reconstruction and Osteotomies for Pes Planovalgus Correction.

The correction of the flexible pes planovalgus foot and ankle is a complicated and somewhat controversial topic. After conservative methods fail, there is a wide range of possible soft tissue and bony procedures. The appropriate work up and understanding of the pathomechanics are vital to the correct choice of procedures to correct these deformities. Once the work up and procedure selection are done, the operation must also be technically performed well and with efficiency, as most often the condition is corrected with a variety of procedures. This article discusses some of the most common procedures necessary to fully correct the pes planovalgus foot and discusses the authors' technique and pearls.

Deformity Correction of the Midfoot/Hindfoot/Ankle.

The correction of the deformed arthritic foot and ankle is a complicated and somewhat controversial topic. After conservative methods fail, there is a wide range of possible bony procedures and arthrodesis that maybe performed. The appropriate work up and understanding of the pathomechanics is vital to the correct choice of procedures to correct these deformities. Once the work up and procedure selection is done, the operation must also be technically performed well and with efficiency, as most often the condition is corrected with a variety of procedures. This article discusses some of the most common procedures necessary to fully correct deformity of the midfoot, hindfoot, and ankle. This article will also discuss the authors' technique and pearls.

Postoperative Infection Rates After Total Ankle Arthroplasty: A Comparison With and Without the Use of a Surgical Helmet System.

Following total joint arthroplasty, surgical site infections (SSI) and periprosthetic joint infections (PJI) are associated with increased patient morbidity and healthcare utilization. Current positive-pressure surgical sterile helmet system (SHS) were developed as a feasible, useful version of the body exhaust system.The use of SHS has not yet been proven to decrease infection rates in the orthopedic literature. The primary purpose of this study is to compare the infection rates between patients who underwent total ankle arthroplasty (TAA) with a surgical team wearing SHS versus without SHS.A retrospective chart review in patients undergoing primary TAA with the surgeon wearing SHS (Group 1) or standard surgical attire (Group 2) was conducted. The primary outcome was postoperative SSI and PJI. The rate of wound complications, revision rates, and associated procedures were also analyzed. We identified 109 patients in Group 1 and 151 patients in Group 2. The rate of SSI was 12.8% in Group 1 and 14.6% in Group 2 (p = .411). The rate of PJI was 0.92% in Group 1 and 2.6% in Group 2 (p = .411). There was no difference in revision rates between the two groups. This study suggests that SHS does not appear to protect against postoperative SSI or PJI after TAA. Conversely, we did not find a higher infection rate compared to standard surgical attire despite recent in-vitro studies suggesting SHS as a source of wound contamination. The utility of SHS does not appear to influence the prevalence of postoperative SSI or PJI.

Knowledge Network Embedding of Transcriptomic Data from Spaceflown Mice Uncovers Signs and Symptoms Associated with Terrestrial Diseases.

There has long been an interest in understanding how the hazards from spaceflight may trigger or exacerbate human diseases. With the goal of advancing our knowledge on physiological changes during space travel, NASA GeneLab provides an open-source repository of multi-omics data from real and simulated spaceflight studies. Alone, this data enables identification of biological changes during spaceflight, but cannot infer how that may impact an astronaut at the phenotypic level. To bridge this gap, Scalable Precision Medicine Oriented Knowledge Engine (SPOKE), a heterogeneous knowledge graph connecting biological and clinical data from over 30 databases, was used in combination with GeneLab transcriptomic data from six studies. This integration identified critical symptoms and physiological changes incurred during spaceflight.

Advancing the Integration of Biosciences Data Sharing to Further Enable Space Exploration.

Understanding the impact of space exploration remains biologically elusive. Cell Press is dedicating this month to spaceflight (Afshinnekoo et al., 2020), with the open science NASA GeneLab database enabling the study revealing mitochondria as a key biological feature from spaceflight (da Silveira et al., 2020).

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

A Comparison of Outcomes of Revision Surgical Options for the Treatment of Failed Bulk Talar Allograft Transfer: A Systematic Review.

Talar bulk osteochondral allograft transplantation is a useful treatment strategy for large, uncontained osteochondral lesions of talus. Complications and high revision rates from osteochondral talar allograft transfer can be common. Talar graft failure is a devastating complication that results from failure of allograft incorporation within the host bone and subsequent resorption and sometimes subsidence can occur. Treatment options and outcomes for graft failure have rarely been reported. The purpose of this study is to evaluate treatment options and their outcomes for treating talar allograft failure. A systematic review was completed to find all reports of salvage treatments for talar graft failure and outcomes of these reports were analyzed. Eleven studies involving a total of 522 ankles, in 520 patients, met the inclusion criteria. The allograft failure rate was 11.5% in these studies with a reoperation rate of 18.9%. With limited reports, satisfactory outcomes for treatment of graft failure with ankle arthrodesis were 77.3%, 50% for revision allograft procedures, and 50% for total ankle arthroplasty. Considering the large failure rate and reoperation rate for bulk talar allograft transplantations, superior revision, and salvage options are needed. More prospective cohort studies focusing on consistent and standard outcome measures are needed to further assess revision options for failed talar allograft procedures.

American College of Foot and Ankle Surgeons Clinical Consensus Statement: Appropriate Clinical Management of Adult-Acquired Flatfoot Deformity.

This clinical consensus statement of the American College of Foot and Ankle Surgeons focuses on the highly debated subject of the management of adult flatfoot (AAFD). In developing this statement, the AAFD consensus statement panel attempted to address the most relevant issues facing the foot and ankle surgeon today, using the best evidence-based literature available. The panel created and researched 16 statements and generated opinions on the appropriateness of the statements. The results of the research on this topic and the opinions of the panel are presented here.

Complications of En Bloc Osteochondral Talar Allografts and Treatment of Failures: Literature Review and Case Report.

Reoperation rates and complication rates can be high for patients receiving an osteochondral talar allograft transplant. Complications can include graft failure, delamination of the graft, arthrofibrosis, advancing osteoarthritis, nonunion of malleolar osteotomies, and partial or complete osteonecrosis of the talus. Graft failure refers to failure of graft incorporation with subsequent necrosis and subsidence. Treatment options for talar graft failure are limited, and outcomes for these treatments have rarely been reported. We present a review of the published data on the complications and treatments for failed talar allograft transplantation. A case report is presented on a young woman who experienced graft failure and osteonecrosis of her talar allograft transplant. Because of the size of the present osteonecrosis, an ankle arthrodesis was performed as the initial revision procedure. Talar necrosis was removed and revascularized from the ankle fusion with solid fusion was confirmed with computed tomography. Symptomatic adjacent joint pain quickly developed in the hindfoot after the ankle fusion, and 12 months later an ankle fusion conversion to total ankle arthroplasty was performed. The patient has returned to normal activity with significant reduction in pain at most recent follow-up visit. This patient was followed for 7 years from initial osteochondral talar allograft transplantation and for 2 years from conversion of ankle fusion to total ankle arthroplasty. It is important to understand the techniques, indications, and outcomes for the various revision options for talar allograft failure. This case report illustrates how multiple revision options can be used to provide the best outcome for the patient.