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.

Trade policy reform, retail food prices and access to healthy diets worldwide.

Recent use of least-cost diets as a measure of global food security revealed that over 3 billion people are unable to afford sufficient nutritious food for an active and healthy life, driving demand for policy changes to improve access and affordability. This study quantifies the role of imports in consumer prices, matching retail prices in 144 countries to imports by origin of the item or its main ingredient, resulting in a total of 13,846 pairs of a retail price and its import cost in 2017. We find that 55% of retail items had some active imports supplementing domestic production, and of those around 48% have nonzero tariffs whose average effective rate is around 6.7% of the imported commodity price. Over all countries for which data are available, the share of consumer prices for least-cost healthy diets that is attributable to tariffs and non-tariff measures averages 0.67% and 2.45% globally. The highest restrictions are on nutrient-rich vegetables, fruits and animal-sourced foods. Access to bulk commodities from diverse origins is essential for food and nutrition security, providing a greater diversity of foods and food ingredients at lower and more stable prices than can be grown at any one location. On average over all food products that are imported, 83% of the retail price is domestic value added after arrival. We conclude that food imports are best understood as inputs to the domestic production and distribution of retail items, with consumer prices and growth of the food sector dependent on the cost levels, infrastructure and institutions underlying each product's entire value chain.

Nurses' perceptions of how their professional autonomy influences the moral dimension of end-of-life care to nursing home residents- a qualitative study.

BACKGROUND: Over the years, caring has been explained in various ways, thus presenting various meanings to different people. Caring is central to nursing discipline and care ethics have always had an important place in nursing ethics discussions. In the literature, Joan Tronto's theory of ethics of care is mostly discussed at the personal level, but there are still a few studies that address its influence on caring within the nursing context, especially during the provision of end-of-life care. This study aims to explore nurses' perceptions of how their professional autonomy influences the moral dimension of end-of-life care provided to nursing home residents. METHODS: This study has a qualitative descriptive design. Data were collected by conducting five individual interviews and one focus group during a seven-month period between April 2022 and September 2022. Nine nurses employed at four Norwegian nursing homes were the participants in this study. Data were analysed by employing a qualitative deductive content analysis method. RESULTS: The content analysis generated five categories that were labelled similar to Tronto's five phases of the care process: (i) caring about, (ii) caring for, (iii) care giving, (iv) care receiving and (v) caring with. The findings revealed that nurses' autonomy more or less influences the decision-making care process at all five phases, demonstrating that the Tronto's theory contributes to greater reflectiveness around what may constitute 'good' end-of-life care. CONCLUSIONS: Tronto's care ethics is useful for understanding end-of-life care practice in nursing homes. Tronto's care ethics provides a framework for an in-depth analysis of the asymmetric relationships that may or may not exist between nurses and nursing home residents and their next-of-kin. This can help nurses see and understand the moral dimension of end-of-life care provided to nursing home residents during their final days. Moreover, it helps handle moral responsibility around end-of-life care issues, providing a more complex picture of what 'good' end-of-life care should be.

Caring to the End: An Empirical Application of Swanson's Caring Theory to End-of-Life Care.

The aim of the current study was to explore the applicability of Swanson's middle-range theory of caring within the context of end-of-life care provided to nursing home residents. A secondary analysis of data collected from 5 individual interviews and 1 focus group with a total of 9 nurses employed at nursing homes was conducted using qualitative deductive content analysis. The findings highlight the influence of nurses' caring attitudes and behaviors on providing end-of-life care, which are described as caring processes. Additionally, the study emphasizes the valuable role of Swanson's theory in guiding end-of-life care practices in nursing homes.

BioSentinel: Validating Sensitivity of Yeast Biosensors to Deep Space Relevant Radiation.

With the imminent human exploration of deep space, it is more important than ever to understand the biological risks of deep space radiation exposure. The BioSentinel mission will be the first biological payload to study the effects of radiation beyond low Earth orbit in 50 years. This study is the last in a collection of articles about the BioSentinel biological CubeSat mission, where budding yeast cells will be used to investigate the response of a biological organism to long-term, low-dose deep space radiation. In this study, we define the methodology for detecting the biological response to space-like radiation using simulated deep space radiation and a metabolic indicator dye reduction assay. We show that there is a dose-dependent decrease in yeast cell growth and metabolism in response to space-like radiation, and this effect is significantly more pronounced in a strain of yeast that is deficient in DNA damage repair (rad51Δ) compared with a wild-type strain. Furthermore, we demonstrate the use of flight-like instrumentation after exposure to space-like ionizing radiation. Our findings will inform the development of novel and improved biosensors and technologies for future missions to deep space.

The lamin A/C Ig-fold undergoes cell density-dependent changes that alter epitope binding.

Lamins A/C are nuclear intermediate filament proteins that are involved in diverse cellular mechanical and biochemical functions. Here, we report that recognition of Lamins A/C by a commonly used antibody (JOL-2) that binds the Lamin A/C Ig-fold and other antibodies targeting similar epitopes is highly dependent on cell density, even though Lamin A/Clevels do not change. We propose that the effect is caused by partial unfolding or masking of the C'E and/or EF loops of the Ig-fold in response to cell spreading. Surprisingly, JOL-2 antibody labeling was insensitive to disruption of cytoskeletal filaments or the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex. Furthermore, neither nuclear stiffness nor nucleo-cytoskeletal force transmission changed with cell density. These findings are important for the interpretation of immunofluorescence data for Lamin A/C and also raise the intriguing prospect that the conformational changes may play a role in Lamin A/C mediated cellular function.

Connecting clinical, environmental, and genetic factors point to an essential role for vitamin A signaling in the pathogenesis of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a developmental disorder that results in incomplete diaphragm formation, pulmonary hypoplasia, and pulmonary hypertension. Although a variety of genes have been linked to its etiology, CDH is not a monogenetic disease, and the cause of the condition is still unclear in the vast majority of clinical cases. By comparing human clinical data and experimental rodent data from the literature, we present clear support demonstrating the importance of vitamin A (vitA) during the early window of pregnancy when the diaphragm and lung are forming. Alteration of vitA signaling via dietary and genetic perturbations can create diaphragmatic defects. Unfortunately, vitA deficiency is chronic among people of child-bearing age, and this early window of diaphragm development occurs before many might be aware of pregnancy. Furthermore, there is an increased demand for vitA during this critical period, which exacerbates the likelihood of deficiency. It would be beneficial for the field to further investigate the connections between maternal vitA and CDH incidence, with the goal of determining vitA status as a CDH risk factor. Regular clinical monitoring of vitA levels in child-bearing years is a tractable method by which CDH outcomes could be prevented or improved.

Zika virus as a cause of birth defects: Were the teratogenic effects of Zika virus missed for decades?

Zika virus (ZIKV) was identified as a teratogen in 2016 when an increase in severe microcephaly and other brain defects was observed in fetuses and newborns following outbreaks in French Polynesia (2013-2014) and Brazil (2015-2016) and among travelers to other countries experiencing outbreaks. Some have questioned why ZIKV was not recognized as a teratogen before these outbreaks: whether novel genetic changes in ZIKV had increased its teratogenicity or whether its association with birth defects had previously been undetected. Here we examine the evidence for these two possibilities. We describe evidence for specific mutations that arose before the French Polynesia outbreak that might have increased ZIKV teratogenicity. We also present information on children born with findings consistent with congenital Zika syndrome (CZS) as early as 2009 and epidemiological evidence that suggests increases in CZS-type birth defects before 2013. We also explore reasons why a link between ZIKV and birth defects might have been missed, including issues with surveillance of ZIKV infections and of birth defects, challenges to ZIKV diagnostic testing, and the susceptibility of different populations to ZIKV infection at the time of pregnancy. Although it is not possible to prove definitively that ZIKV had teratogenic properties before 2013, several pieces of evidence support the hypothesis that its teratogenicity had been missed in the past. These findings emphasize the need for further investments in global surveillance for emerging infections and for birth defects so that infectious teratogens can be identified more expeditiously in the future.

Artificial gravity partially protects space-induced neurological deficits in Drosophila melanogaster.

Spaceflight poses risks to the central nervous system (CNS), and understanding neurological responses is important for future missions. We report CNS changes in Drosophila aboard the International Space Station in response to spaceflight microgravity (SFµg) and artificially simulated Earth gravity (SF1g) via inflight centrifugation as a countermeasure. While inflight behavioral analyses of SFµg exhibit increased activity, postflight analysis displays significant climbing defects, highlighting the sensitivity of behavior to altered gravity. Multi-omics analysis shows alterations in metabolic, oxidative stress and synaptic transmission pathways in both SFµg and SF1g; however, neurological changes immediately postflight, including neuronal loss, glial cell count alterations, oxidative damage, and apoptosis, are seen only in SFµg. Additionally, progressive neuronal loss and a glial phenotype in SF1g and SFµg brains, with pronounced phenotypes in SFµg, are seen upon acclimation to Earth conditions. Overall, our results indicate that artificial gravity partially protects the CNS from the adverse effects of spaceflight.

Multi-system responses to altered gravity and spaceflight: Insights from Drosophila melanogaster.

NASA is planning to resume human-crewed lunar missions and lay the foundation for human exploration to Mars. However, our knowledge of the overall effects of long-duration spaceflight on human physiology is limited. During spaceflight, astronauts are exposed to multiple risk factors, including gravitational changes, ionizing radiation, physiological stress, and altered circadian lighting. These factors contribute to pathophysiological responses that target different organ systems in the body. This review discusses the advancements in gravitational biology using Drosophila melanogaster, one of the first organisms to be launched into space. As a well-established spaceflight model organism, fruit flies have yielded significant information, including neurobehavioral, aging, immune, cardiovascular, developmental, and multi-omics changes across tissues and developmental stages, as detailed in this review.

Asparagine biosynthesis as a mechanism of increased host lethality induced by Serratia marcescens in simulated microgravity environments.

While studies have shown an increase in pathogenicity in several microbes during spaceflight and after exposure to simulated microgravity, the mechanisms underlying these changes in phenotype are not understood across different pathogens, particularly in opportunistic pathogens. This study evaluates the mechanism for increased virulence of the opportunistic gram-negative bacterium, Serratia marcescens, in simulated microgravity. Low-shear modeled microgravity (LSMMG) is used in ground-based studies to simulate the effects of microgravity as experienced in spaceflight. Our previous findings showed that there was a significant increase in mortality rates of the Drosophila melanogaster host when infected with either spaceflight or LSMMG treated S. marcescens. Here, we report that LSMMG increases asparagine uptake and synthesis in S. marcescens and that the increased host lethality induced by LSMMG bacteria grown in rich media can be recapitulated in minimal media by adding only aspartate and glutamine, the substrates of asparagine biosynthesis. Interestingly, increased bacterial growth rate alone is not sufficient to contribute to maximal host lethality, since the addition of aspartate to minimal media caused an LSMMG-specific increase in bacterial growth rate that is comparable to that induced by the combination of aspartate and glutamine, but this increase in growth does not cause an equivalent rate of host mortality. However, the addition of both aspartate and glutamine cause both an increase in host mortality and an overexpression of asparagine pathway genes in a LSMMG-dependent manner. We also report that L-asparaginase-mediated breakdown of asparagine is an effective countermeasure for the increased host mortality caused by LSMMG-treated bacteria. This investigation underscores the importance of the asparagine utilization pathway by helping uncover molecular mechanisms that underlie increased mortality rates of a model host infected with microgravity-treated S. marcescens and provides a potential mitigation strategy.

A preliminary randomized, controlled trial of executive function training for children with autism spectrum disorder.

LAY ABSTRACT: Executive function, which is a set of thinking skills that includes stopping unwanted responses, being flexible, and remembering information needed to solve problems, is a challenge for many children on the autism spectrum. This study tested whether executive function could be improved with a computerized executive function training program under the guidance of a coach who reinforced the use of executive function skills. Seventy children with autism spectrum disorder from age 7 to 11 years of age participated in the study. They were randomly assigned to receive training or to a waiting group. The tests most likely to determine whether the training may be effective were chosen from a larger battery before the study started and included one task measuring brain responses, two measures of executive function in the lab, and a parent questionnaire. Changes in social functioning and repetitive behaviors were also explored. All children assigned to training completed the program and families generally reported the experience was positive. Brain responses of the training group changed following training, but not within the waiting group during a similar time period. Children who received training did not exhibit behavioral changes during the two the lab-based tasks. Parent report on questionnaires indicated that neither group showed a significant change in their broad use of executive function in other settings. Yet, children who received training were reported to have fewer restricted and repetitive behaviors following training. These initial findings suggest that short executive function training activities are feasible and may improve some functioning of school-aged children on the autism spectrum.

Resting frontal alpha asymmetry as a predictor of executive and affective functioning in children with neurodevelopmental differences.

The relative difference of resting EEG frontal alpha activation between left and right hemispheres (FAA; i.e., asymmetry) correlates with global approach and avoidance tendencies. FAA may relate to problems with executive and affective functioning in children with neurodevelopmental differences, including autism and ADHD. We (1) characterize relative left vs. right FAA in autistic, ADHD, and neurotypical children (NT) and (2) investigate whether FAA predicts "hot" executive function or emotion dysregulation. Participants were 97 7- to 11-year-old autistic, ADHD, and NT Children. Children with ADHD displayed greater left (relative to right) FAA compared to autistic and neurotypical children. Children with ADHD displayed greater challenges with "hot" EF on a gambling task than autistic children, whereas children with co-occurring autism and ADHD had greater parent-reported emotion dysregulation than NT and autism-only groups. Greater left FAA predicted worse hot EF for all children but was not significantly related to emotion dysregulation. Regardless of clinical diagnosis, relatively greater left FAA relates to hot EF. While hot EF deficits may be specific to ADHD rather than autism, both together confer additive risk for emotion dysregulation. Future research should explore the functional relation between FAA, reward processing, and affect for children with different EF-related neurodevelopmental differences.

Mammalian and Invertebrate Models as Complementary Tools for Gaining Mechanistic Insight on Muscle Responses to Spaceflight.

Bioinformatics approaches have proven useful in understanding biological responses to spaceflight. Spaceflight experiments remain resource intensive and rare. One outstanding issue is how to maximize scientific output from a limited number of omics datasets from traditional animal models including nematodes, fruitfly, and rodents. The utility of omics data from invertebrate models in anticipating mammalian responses to spaceflight has not been fully explored. Hence, we performed comparative analyses of transcriptomes of soleus and extensor digitorum longus (EDL) in mice that underwent 37 days of spaceflight. Results indicate shared stress responses and altered circadian rhythm. EDL showed more robust growth signals and Pde2a downregulation, possibly underlying its resistance to atrophy versus soleus. Spaceflight and hindlimb unloading mice shared differential regulation of proliferation, circadian, and neuronal signaling. Shared gene regulation in muscles of humans on bedrest and space flown rodents suggest targets for mitigating muscle atrophy in space and on Earth. Spaceflight responses of C. elegans were more similar to EDL. Discrete life stages of D. melanogaster have distinct utility in anticipating EDL and soleus responses. In summary, spaceflight leads to shared and discrete molecular responses between muscle types and invertebrate models may augment mechanistic knowledge gained from rodent spaceflight and ground-based studies.

Impacts of COVID-19 induced income and rice price shocks on household welfare in Papua New Guinea: Household model estimates.

Concerns over the potential effects of the COVID-19 pandemic have led to trade restrictions by major rice exporters, contributing to an average 25% increase in Thai and Vietnamese rice export prices between December 2019 and March-September 2020. This article assesses the consequences of these rice price increases in Papua New Guinea (PNG), where 99% of rice is imported. Utilizing data from a PNG 2018 rural household survey along with earlier national household survey data, we examine rice consumption patterns in PNG and estimate demand parameters for urban and rural households. Model simulations indicate that a 25% rise in the world price of rice would reduce total rice consumption in PNG by 14% and reduce rice consumption of the poor (bottom 40% of total household expenditure distribution) by 15%. Including the effects of a possible 12% decrease in household incomes because of the COVID-19 related economic slowdown, rice consumption of the urban and rural poor fall by 20% and 17%, respectively. Maintaining functioning domestic supply chains of key staple goods is critical to mitigating the effects of global rice price increases, allowing urban households to increase their consumption of locally produced staples.

Defective mesothelium and limited physical space are drivers of dysregulated lung development in a genetic model of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a developmental disorder associated with diaphragm defects and lung hypoplasia. The etiology of CDH is complex and its clinical presentation is variable. We investigated the role of the pulmonary mesothelium in dysregulated lung growth noted in the Wt1 knockout mouse model of CDH. Loss of WT1 leads to intrafetal effusions, altered lung growth, and branching defects prior to normal closure of the diaphragm. We found significant differences in key genes; however, when Wt1 null lungs were cultured ex vivo, growth and branching were indistinguishable from wild-type littermates. Micro-CT imaging of embryos in situ within the uterus revealed a near absence of space in the dorsal chest cavity, but no difference in total chest cavity volume in Wt1 null embryos, indicating a redistribution of pleural space. The altered space and normal ex vivo growth suggest that physical constraints are contributing to the CDH lung phenotype observed in this mouse model. These studies emphasize the importance of examining the mesothelium and chest cavity as a whole, rather than focusing on single organs in isolation to understand early CDH etiology.

NASA GeneLab RNA-seq consensus pipeline: standardized processing of short-read RNA-seq data.

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility, and reusability of pipeline data; to provide a template for data processing of future spaceflight-relevant datasets; and to encourage cross-analysis of data from other databases with the data available in GeneLab.

Targeted Gq-GPCR activation drives ER-dependent calcium oscillations in chondrocytes.

The temporal dynamics of calcium signaling are critical regulators of chondrocyte homeostasis and chondrogenesis. Calcium oscillations regulate differentiation and anabolic processes in chondrocytes and their precursors. Attempts to control chondrocyte calcium signaling have been achieved through mechanical perturbations and synthetic ion channel modulators. However, such stimuli can lack both local and global specificity and precision when evoking calcium signals. Synthetic signaling platforms can more precisely and selectively activate calcium signaling, enabling improved dissection of the roles of intracellular calcium ([Ca2+]i) in chondrocyte behavior. One such platform is hM3Dq, a chemogenetic DREADD (Designer Receptors Exclusively Activated by Designer Drugs) that activates calcium signaling via the Gαq-PLCß-IP3-ER pathway upon administration of clozapine N-oxide (CNO). We previously described the first-use of hM3Dq to precisely mediate targeted, synthetic calcium signals in chondrocyte-like ATDC5 cells. Here, we generated stably expressing hM3Dq-ATDC5 cells to investigate the dynamics of Gαq-GPCR calcium signaling in depth. CNO drove robust calcium responses in a temperature- and concentration-dependent (1 pM-100 µM) manner and elicited elevated levels of oscillatory calcium signaling above 10 nM. hM3Dq-mediated calcium oscillations in ATDC5 cells were reliant on ER calcium stores for both initiation and sustenance, and the downregulation and recovery dynamics of hM3Dq after CNO stimulation align with traditionally reported GPCR recycling kinetics. This study successfully generated a stable hM3Dq cell line to precisely drive Gαq-GPCR-mediated and ER-dependent oscillatory calcium signaling in ATDC5 cells and established a novel tool to elucidate the role that GPCR-mediated calcium signaling plays in chondrocyte biology, cartilage pathology, and cartilage tissue engineering.

Inhibition in developmental disorders: A comparison of inhibition profiles between children with autism spectrum disorder, attention-deficit/hyperactivity disorder, and comorbid symptom presentation.

LAY ABSTRACT: Many children with autism spectrum disorder (ASD) also have symptoms of attention-deficit hyperactivity disorder (ADHD). Children with ASD and ADHD often experience difficulties with inhibition. This study had the goal of understanding inhibition in children with ASD, ADHD, ASD + ADHD, and children who are typically developing (TD) using tasks that measured several aspects of inhibition. Results indicate that children with ASD + ADHD had greater difficulty inhibiting behavioral responses than TD children. Children with ASD + ADHD also differed from children with ASD and with ADHD in their inhibition of distracting information and strategic slowing of response speed. The four groups did not differ in their avoidance of potential losses. Children with ASD + ADHD exhibit a unique profile of inhibition challenges suggesting they may benefit from targeted intervention matched to their abilities.

Mask Reuse in the COVID-19 Pandemic: Creating an Inexpensive and Scalable Ultraviolet System for Filtering Facepiece Respirator Decontamination.

As the current COVID-19 pandemic illustrates, not all hospitals and other patient care facilities are equipped with enough personal protective equipment to meet the demand in a crisis. Health care workers around the world use filtering facepiece respirators to protect themselves and their patients, yet during this global pandemic they are forced to reuse what are intended to be single-use masks. This poses a significant risk to these health care workers along with the people they are trying to protect. Ultraviolet germicidal irradiation (UVGI) has been validated previously as a method to effectively decontaminate these masks between use. However, not all facilities have access to the expensive commercial ultraviolet type C (UV-C) lamp decontamination equipment required for UVGI. UV-C bulbs are sitting idle in biosafety cabinets at universities and research facilities around the world that have been shuttered to slow the spread of COVID-19. These bulbs may also be available in existing medical centers where infectious diseases are commonly treated. We developed a method to modify existing light fixtures or create custom light fixtures that are compatible with new or existing UV-C bulbs. This system is scalable; can be created for less than US$50, on site and at the point of need; and leverages resources that are currently untapped and sitting unused in public and private research facilities during the pandemic. The freely accessible design can be easily modified for use around the world. Health care facilities can obtain this potentially lifesaving UVGI resource with minimal funds by collaborating with research facilities to obtain the UV-C meters and UV-C bulbs if they are unavailable from other sources. Although mask reuse is not ideal, we must do what we can in emergency situations to protect our health care workers responding to the pandemic and the communities they serve.