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Investment in spacefaring enterprises must offer transformative solutions to Earth-based challenges. Providing for the future health of our home planet is possibly the greatest return on investment. Therefore, ensuring that the large costs of astronautics also yield benefits on Earth is critical. The goal of space bioprocess engineering is the design, realization and management of biologically driven technologies for supporting off-world human exploration. Here, we outline several technologies with high dual-use potential, argue that continued investment in such technologies is justified, and offer insight into specific research and development strategies that will increase sociological, political and technological benefits for sustainable development on Earth.

This mixed methods study describes the development and initial validation of the Culture of Belonging (CoB) Barometer. The instrument measures how university students experience belonging in their interactions with faculty, staff, administrators, and other students. Instrument development methods included focus groups, a pilot survey, and stakeholder feedback. Initial validation of the CoB Barometer shows promising results.

Abstract Background Dry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis. The purpose of this study was to evaluate efficacy and safety of cenegermin in moderate-to-severe DED and identify an optimal dosing strategy. Methods This was a phase II, multicenter, randomized, double-masked, vehicle-controlled, dose-ranging clinical trial in patients with moderate-to-severe DED, including Sjögren’s DED (NCT03982368). Patients received 1 drop of cenegermin 3 times daily (t.i.d.; 20 mcg/mL), cenegermin 2 times daily (b.i.d.; 20 mcg/mL) and vehicle once daily, or vehicle t.i.d. for 4 weeks. Follow-up continued for 12 additional weeks. The primary endpoint was change in Schirmer I score from baseline to week 4. Other key endpoints included rate of responders (Schirmer I test > 10 mm/5 min) after treatment and change in Symptoms Assessment iN Dry Eye (SANDE) scores from baseline to end of follow-up. A 1-sided test (α = 0.025) was used to evaluate statistical significance. Results At week 4, mean changes in Schirmer I scores were not statistically significantly different in either cenegermin group versus vehicle (cenegermin vs vehicle [treatment difference; 95% CI]: t.i.d., 2.60 mm and b.i.d., 3.99 mm vs 1.68 mm [t.i.d.: 0.93; −1.47 to 3.32, P = 0.078; b.i.d.: 2.31; −0.08 to 4.70, P = 0.066]). More patients responded to treatment with cenegermin t.i.d. and b.i.d. versus vehicle (t.i.d.: 25.9% [21/81, P = 0.028]; b.i.d.: 29.3% [24/82, P = 0.007] vs 11.9% [10/84]), with statistical significance (set at P

OBJECTIVES: Type I interferon (IFN) plays a role in the pathogenesis of systemic lupus erythematosus (SLE), but insufficient attention has been directed to the differences in IFN responses between ancestral populations. Here, we explored the expression of the interferon gene signatures (IGSs) in SLE patients of European ancestry (EA) and Asian ancestry (AsA). METHODS: We used gene set variation analysis with multiple IGS encompassing the response to both type 1 and type 2 IFN in isolated CD14+ monocytes, CD19+B cells, CD4+T cells and Natural Killer (NK) cells from patients with SLE stratified by self-identified ancestry. The expression of genes upstream of the IGS and influenced by lupus-associated risk alleles was also examined. Lastly, we employed machine learning (ML) models to assess the most important features classifying patients by disease activity. RESULTS: AsA patients with SLE exhibited greater enrichment in the IFN core and IFNA2 IGS compared with EA patients in all cell types examined and, in the presence and absence of autoantibodies. Overall, AsA patients with SLE demonstrated higher expression of genes upstream of the IGS than EA counterparts. ML with feature importance analysis indicated that IGS expression in NK cells, anti-dsDNA, complement levels and AsA status contributed to disease activity. CONCLUSIONS: AsA patients with SLE exhibited higher IGS than EA patients in all cell types regardless of autoantibody status, with enhanced expression of genetically associated genes upstream of the IGS potentially contributing. AsA, along with the IGS in NK cells, anti-dsDNA and complement, independently influenced SLE disease activity.

Traumatic brain injury (TBI) has reached epidemic proportions worldwide. The consequences of TBI can be severe even with repetitive mild trauma. If death and coma are avoided, the consequences of TBI in the long term typically involve dizziness, sleep disturbances, headache, seizures, cognitive impairment, focal deficits, depression, and anxiety. The severity of brain injury is a significant predictor of outcome. However, the heterogenous nature of the injury makes prognosis difficult. The present review of the literature focuses on the genetics of TBI including genome wide (GWAS) data and candidate gene associations, among them brain-derived neurotrophic factor (BDNF) with TBI and development of post-traumatic epilepsy (PTE). Molecular biomarkers of TBI are also discussed with a focus on proteins and the inflammatory protein IL1-β. The secondary medical sequela to TBI of cognitive impairment, PTE, headache and risk for neurodegenerative disorders is also discussed. This overview of TBI concludes with a review and discussion of the medical management of TBI and the medicines used for and being developed at the preclinical and clinical stages for the treatment of TBI and its host of life-debilitating symptoms.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of Asian-Ancestry (AsA) disproportionately experience more severe SLE compared to individuals of European-Ancestry (EA), including increased renal involvement and tissue damage. However, the mechanisms underlying elevated severity in the AsA population remain unclear. Here, we utilized available gene expression data and genotype data based on all non-HLA SNP associations in EA and AsA SLE patients detected using the Immunochip genotyping array. We identified 2778 ancestry-specific and 327 trans-ancestry SLE-risk polymorphisms. Genetic associations were examined using connectivity mapping and gene signatures based on predicted biological pathways and were used to interrogate gene expression datasets. SLE-associated pathways in AsA patients included elevated oxidative stress, altered metabolism and mitochondrial dysfunction, whereas SLE-associated pathways in EA patients included a robust interferon response (type I and II) related to enhanced cytosolic nucleic acid sensing and signaling. An independent dataset derived from summary genome-wide association data in an AsA cohort was interrogated and identified similar molecular pathways. Finally, gene expression data from AsA SLE patients corroborated the molecular pathways predicted by SNP associations. Identifying ancestry-related molecular pathways predicted by genetic SLE risk may help to disentangle the population differences in clinical severity that impact AsA and EA individuals with SLE.

Drug development in lupus has improved over the past 10 years but still lags behind that of other rheumatic disease areas. Assessment of prospective lupus therapies in clinical trials has proved challenging for reasons that are multifactorial including the heterogeneity of the disease, study design limitations and a lack of validated biomarkers which greatly impacts regulatory decision-making. Moreover, most composite outcome measures currently used in trials do not include patient-reported outcomes. Given these factors, the Addressing Lupus Pillars for Health Advancement Global Advisory Committee members who serve on the drug development team identified an opportunity to convene a meeting to facilitate information sharing on completed and existing outcome measure development efforts. This meeting report highlights information presented during the meeting as well as a discussion on how the lupus community may work together with regulatory agencies to simplify and standardise outcome measures to accelerate development of lupus therapeutics.

Background:. On Saturday, October 7th, approximately 3000 Hamas-led terrorists infiltrated Israel’s southern border and attacked civilians and soldiers. Terrorists murdered close to 1200 people, abducted hundreds, and injured thousands. This surprise attack involved an unprecedented number of casualties. This article describes the injuries and outcomes of the hospitalized casualties. Methods:. Hospitalized trauma casualties with an injury date of October 7 to 8, 2023, and with ICD9 E-codes E979 and E990 through E999, were extracted from the Israel National Trauma Registry. Demographic, injury, and hospital resource-use data were analyzed. Results:. A total of 630 hospitalized casualties (277 civilians and 353 soldiers) suffered from gunshot wounds (90%), explosion-related wounds (19%), and multiple injury mechanisms (16%). The median age for civilians was 33 years (ages

Summary: Autoimmune patients have a significantly increased risk of developing coronary artery disease (CAD) compared to the general population. However, autoimmune patients often lack traditional risk factors for CAD and there is increasing recognition of inflammation in CAD development. In this study, we leveraged genome-wide association study (GWAS) data to understand whether there is a genetic relationship between CAD and autoimmunity. Statistical genetic comparison methods were used to identify correlated and causal SNPs between various autoimmune diseases and CAD. Pleiotropic SNPs were identified by cross-phenotype association analysis (CPASSOC) and overlap between GWAS. Causal SNPs were identified using Mendelian Randomization (MR) and Colocalization (COLOC). Using SNP-to-gene mapping, we additionally identified pleiotropic and causal genes and pathways associated between autoimmunity and CAD, which were contextualized by documentation of enrichment in individual cell types identified from coronary atherosclerotic plaques by single-cell RNA sequencing. These results provide insight into potential inflammatory therapeutic targets for CAD.

Objective Omega-3 polyunsaturated fatty acids (PUFAs) play a critical role in regulating inflammation and lipid metabolism. This study sought to ascertain the frequency of omega-3 deficiency in patients with SLE and investigate whether supplementation with krill oil concentrate (KOC) could replenish omega-3 levels and decrease SLE disease activity.Methods A multicentre, randomised, double-blind, placebo-controlled trial was conducted in adult patients with active SLE. Eligible patients were randomised to receive 4 g/day KOC or placebo (vegetable oil mixture) for the first 24 weeks, and thereafter patients could opt to enter an open-label extension. The primary end point was improvement of the red blood cell Omega-3 Index from baseline to week 24. Changes in clinical features, including SLE Disease Activity Index 2000 (SLEDAI-2K) disease activity scores, were also monitored.Results Seventy-eight patients met eligibility criteria and were randomised to a treatment group (n=39 per group). The baseline Omega-3 Index in the total SLE cohort was a mean 4.43% (±SD 1.04%). After 4 weeks of KOC treatment, the Omega-3 Index rapidly increased to 7.17%±1.48% (n=38) and after 24 weeks to 8.05%±1.79% (n=25) (each p

The autoimmune disease lupus erythematosus (lupus) is characterized by photosensitivity, where even ambient ultraviolet radiation (UVR) exposure can lead to development of inflammatory skin lesions. We have previously shown that Langerhans cells (LCs) limit keratinocyte apoptosis and photosensitivity via a disintegrin and metalloprotease 17 (ADAM17)-mediated release of epidermal growth factor receptor (EGFR) ligands and that LC ADAM17 sheddase activity is reduced in lupus. Here, we sought to understand how the lupus skin environment contributes to LC ADAM17 dysfunction and, in the process, differentiate between effects on LC ADAM17 sheddase function, LC ADAM17 expression, and LC numbers. We show through transcriptomic analysis a shared IFN-rich environment in non-lesional skin across human lupus and three murine models: MRL/lpr, B6.Sle1yaa, and imiquimod (IMQ) mice. IFN-I inhibits LC ADAM17 sheddase activity in murine and human LCs, and IFNAR blockade in lupus model mice restores LC ADAM17 sheddase activity, all without consistent effects on LC ADAM17 protein expression or LC numbers. Anti-IFNAR-mediated LC ADAM17 sheddase function restoration is associated with reduced photosensitive responses that are dependent on EGFR signaling and LC ADAM17. Reactive oxygen species (ROS) is a known mediator of ADAM17 activity; we show that UVR-induced LC ROS production is reduced in lupus model mice, restored by anti-IFNAR, and is cytoplasmic in origin. Our findings suggest that IFN-I promotes photosensitivity at least in part by inhibiting UVR-induced LC ADAM17 sheddase function and raise the possibility that anifrolumab ameliorates lupus skin disease in part by restoring this function. This work provides insight into IFN-I-mediated disease mechanisms, LC regulation, and a potential mechanism of action for anifrolumab in lupus.

Abstract: Space bioprocess engineering (SBE) is an emerging multi-disciplinary field to design, realize, and manage biologically-driven technologies specifically with the goal of supporting life on long term space missions. SBE considers synthetic biology and bioprocess engineering under the extreme constraints of the conditions of space. A coherent strategy for the long term development of this field is lacking. In this Perspective, we describe the need for an expanded mandate to explore biotechnological needs of the future missions. We then identify several key parameters—metrics, deployment, and training—which together form a pathway towards the successful development and implementation of SBE technologies of the future.

Abstract Background Systemic lupus erythematosus (SLE) is known to be clinically heterogeneous. Previous efforts to characterize subsets of SLE patients based on gene expression analysis have not been reproduced because of small sample sizes or technical problems. The aim of this study was to develop a robust patient stratification system using gene expression profiling to characterize individual lupus patients. Methods We employed gene set variation analysis (GSVA) of informative gene modules to identify molecular endotypes of SLE patients, machine learning (ML) to classify individual patients into molecular subsets, and logistic regression to develop a composite metric estimating the scope of immunologic perturbations. SHapley Additive ExPlanations (SHAP) revealed the impact of specific features on patient sub-setting. Results Using five datasets comprising 2183 patients, eight SLE endotypes were identified. Expanded analysis of 3166 samples in 17 datasets revealed that each endotype had unique gene enrichment patterns, but not all endotypes were observed in all datasets. ML algorithms trained on 2183 patients and tested on 983 patients not used to develop the model demonstrated effective classification into one of eight endotypes. SHAP indicated a unique array of features influential in sorting individual samples into each of the endotypes. A composite molecular score was calculated for each patient and significantly correlated with standard laboratory measures. Significant differences in clinical characteristics were associated with different endotypes, with those with the least perturbed transcriptional profile manifesting lower disease severity. The more abnormal endotypes were significantly more likely to experience a severe flare over the subsequent 52 weeks while on standard-of-care medication and specific endotypes were more likely to be clinical responders to the investigational product tested in one clinical trial analyzed (tabalumab). Conclusions Transcriptomic profiling and ML reproducibly separated lupus patients into molecular endotypes with significant differences in clinical features, outcomes, and responsiveness to therapy. Our classification approach using a composite scoring system based on underlying molecular abnormalities has both staging and prognostic relevance.

Inspired by new measurements and imagery from the Perseverance mission, there is reinvigorated public interest in a crewed mission to Mars in the 2040s. To realize such a mission, we must work to solve multiple science and engineering challenges as described by NASA's Space Technology Grand Challenges (STGCs) for expanding human presence in space, centered around advancing technologies to support the nutritional, medical, and incidental material requirements that will sustain astronauts against the harsh conditions of interplanetary transit and habitation on the surface of an inhospitable alien world. Advanced biotechnologies that support flexible biomanufacturing from in situ resources can provide a mass, power, and volume advantage compared to traditional physicochemical strategies. However, critical bottlenecks remain that must be overcome to make Mars biomanufacturing practical and robust. Here we begin with a brief review of the recently codified field of Space Bioprocess Engineering (SBE) - the multidisciplinary approach for the design, realization, and technical management of a biologically-driven system in a space mission context - and we outline the concept of “Hilbert-like” problems that may shape the field in the future. We then describe a number of categories for such problems and expand on a number of preliminary Mission Design and Modeling problems that underpin SBE, in the fields of mission architecture formation and value benchmarking. We end by enumerating a list of problems and challenges across Mission Design and Modeling (MDM), In Situ Resource Utilization (ISRU), In Situ Manufacturing (ISM), Food and Pharmaceutical Synthesis (FPS), and Sustainability and Loop Closure (SLC). The Space Bioprocess Engineering problems provided here are based on an effort by the Center for the Utilization of Biological Engineering in Space (CUBES, https://cubes.space/). We recognize that more feedback is needed to better define the envelope and specifics of SBE challenges for the field, and we provide a link to a set of questions here: https://forms.gle/YKtuPU9MXZ3mi7gE6.

Background: The coronavirus (COVID-19) pandemic created challenges for healthcare providers, especially dental professionals in practices and universities. This study investigated dental students’ concerns about COVID-19 and whether institutional communication influenced pandemic-related stressors. Methods: An online survey designed to elicit dental students’ concerns about COVID-19 was distributed to all dental students enrolled at a private non-profit academic institution in the Western United States from 26 April 2021 to 25 August 2021. Descriptive statistics were used to characterize the respondents, and Chi-square test and z-test analyses were used to compare students’ experiences. Results: A total of 92 dental students answered the survey. The respondents’ ages ranged from 22 to 47 years. Slightly more than half (50.5%) were male and 93.3% were non-Hispanic or non-Latino. Over one-fourth of the students (27.5%) reported that they either often or always felt anxious that they might become infected with the COVID-19 virus, with 16.3% of the students expressing concern about contracting COVID-19 while on campus. There were no statistically significant differences in anxiety levels about contracting COVID-19 from clinic patients or while on campus between the group of students who perceived the institution communicated effectively and those who did not. However, students who felt that the dental school clearly communicated COVID-19 protocols were more likely to believe that students took protocols seriously and expressed less concern about contracting COVID-19 by touching dental school items. Conclusions: About one-quarter of dental students expressed high levels of anxiety about being infected with COVID-19. Clear communication about COVID-19 protocols reduced students’ fear of contracting COVID-19 from dental school items and strengthened their belief that other students followed protocols.