How etiological beliefs contribute to the structure of depression symptom networks.

OBJECTIVES: Each person possesses a unique view surrounding depressive symptomology and etiology that is shaped by idiosyncratic experiences. However, the influence that subjective etiological beliefs regarding a person's depressive symptoms have on actual symptom presentation and organization is seldom considered. METHODS: The current study employed network analytic techniques to examine how subjective views surrounding the cause of depressive symptoms altered actual symptom presentation networks. Additionally, the interaction between depressive symptoms and various etiological beliefs was examined. RESULTS: The results revealed that characterological beliefs, representing the idea that depression is caused by an internal sense of self, are strongly connected to a negative view of self, as well as a saddened mood. Additionally, the characterological beliefs node exhibited the greatest node predictability in its respective network, as well as in an omnibus network consisting of all depression symptoms and potential etiological beliefs. Whereas an achievement-based view of depression has a strong connection with concentration difficulties, a physical view of depression tends to form strong connections with physically based depressive symptoms. CONCLUSION: Subjective views regarding the cause of depression have the potential to influence symptom presentation and organization within a network, which may influence a person's willingness to engage in treatment or specific treatment preferences.

Providing insights into health data science education through artificial intelligence.

BACKGROUND: Health Data Science (HDS) is a novel interdisciplinary field that integrates biological, clinical, and computational sciences with the aim of analysing clinical and biological data through the utilisation of computational methods. Training healthcare specialists who are knowledgeable in both health and data sciences is highly required, important, and challenging. Therefore, it is essential to analyse students' learning experiences through artificial intelligence techniques in order to provide both teachers and learners with insights about effective learning strategies and to improve existing HDS course designs. METHODS: We applied artificial intelligence methods to uncover learning tactics and strategies employed by students in an HDS massive open online course with over 3,000 students enrolled. We also used statistical tests to explore students' engagement with different resources (such as reading materials and lecture videos) and their level of engagement with various HDS topics. RESULTS: We found that students in HDS employed four learning tactics, such as actively connecting new information to their prior knowledge, taking assessments and practising programming to evaluate their understanding, collaborating with their classmates, and repeating information to memorise. Based on the employed tactics, we also found three types of learning strategies, including low engagement (Surface learners), moderate engagement (Strategic learners), and high engagement (Deep learners), which are in line with well-known educational theories. The results indicate that successful students allocate more time to practical topics, such as projects and discussions, make connections among concepts, and employ peer learning. CONCLUSIONS: We applied artificial intelligence techniques to provide new insights into HDS education. Based on the findings, we provide pedagogical suggestions not only for course designers but also for teachers and learners that have the potential to improve the learning experience of HDS students.

High-Strength Organic-Inorganic Composites with Superior Thermal Insulation and Acoustic Attenuation.

We demonstrate facile fabrication of highly filled, lightweight organic-inorganic composites comprising polyurethanes covalently linked with naturally occurring clinoptilolite microparticles. These polyurethane/clinoptilolite (PUC) composites are shown to mitigate particle aggregation usually observed in composites with high particle loadings and possess enhanced thermal insulation and acoustic attenuation compared with conventionally employed materials (e.g., drywall and gypsum). In addition to these functional properties, the PUC composites also possess flexural strengths and strain capacities comparable to and higher than ordinary Portland cement (OPC), respectively, while being ∼1.5× lighter than OPC. The porosity, density, and mechanical and functional properties of these composites are tuned by systematically varying their composition (diisocyanate, polyurethane, and inorganic contents) and the nature of the organic (reactivity and source of polyol) components. The fabrication process involves mild curing conditions and uses commonly available reagents (naturally occurring aluminosilicate particles, polyols, and diisocyanate), thereby making the process scalable. Finally, the composite properties are shown to be independent of the polyol source (virgin or recycled), underlining the generality of this approach for the scalable utilization of recycled polyols.

P53 and TLR4 expression are prognostic markers informing progression free survival of advanced stage high grade serous ovarian cancer.

OBJECTIVE: New prognostic biomarkers, and bio-signatures, are urgently needed to facilitate a precision medicine-based approach to more effectively treat patients with high-grade serous ovarian cancer (HGSC). In this study, we analysed the expression patterns of a series of candidate protein biomarkers. METHODS: The panel of markers which included MyD88, TLR4, MAD2, PR, OR, WT1, p53, p16, CD10 and Ki67 was assessed using immunohistochemistry in a tissue microarray (TMA) cohort of n = 80 patients, composed of stage 3-4 HGSCs. Each marker was analysed for their potential to predict both overall survival (OS) and progression-free survival (PFS). RESULTS: TLR4 and p53 were found to be individually predictive of poorer PFS (Log Rank, p = 0.017, p = 0.030 respectively). Cox regression analysis also identified high p53 and TLR4 expression as prognostic factors for reduced PFS (p53; HR=1.785, CI=1.036-3.074, p = 0.037 and TLR4; HR=2.175, CI=1.112-4.253, p = 0.023). Multivariate forward conditional Cox regression analysis, examining all markers, identified a combined signature composed of p53 and TLR4 as prognostic for reduced PFS (p = 0.023). CONCLUSION: Combined p53 and TLR4 marker assessment may help to aid treatment stratification for patients diagnosed with advanced-stage HGSC.

Testing for Allele-specific Expression from Human Brain Samples.

Many single nucleotide polymorphisms (SNPs) identified by genome-wide association studies exert their effects on disease risk as expression quantitative trait loci (eQTL) via allele-specific expression (ASE). While databases for probing eQTLs in tissues from normal individuals exist, one may wish to ascertain eQTLs or ASE in specific tissues or disease-states not characterized in these databases. Here, we present a protocol to assess ASE of two possible target genes (GPNMB and KLHL7) of a known genome-wide association study (GWAS) Parkinson's disease (PD) risk locus in postmortem human brain tissue from PD and neurologically normal individuals. This was done using a sequence of RNA isolation, cDNA library generation, enrichment for transcripts of interest using customizable cDNA capture probes, paired-end RNA sequencing, and subsequent analysis. This method provides increased sensitivity relative to traditional bulk RNAseq-based and a blueprint that can be extended to the study of other genes, tissues, and disease states. Key features • Analysis of GPNMB allele-specific expression (ASE) in brain lysates from cognitively normal controls (NC) and Parkinson's disease (PD) individuals. • Builds on the ASE protocol of Mayba et al. (2014) and extends application from cells to human tissue. • Increased sensitivity by enrichment for desired transcript via RNA CaptureSeq (Mercer et al., 2014). • Optimized for human brain lysates from cingulate gyrus, caudate nucleus, and cerebellum.

Continuous observations of the surface energy budget and meteorology over the Arctic sea ice during MOSAiC.

The Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) was a yearlong expedition supported by the icebreaker R/V Polarstern, following the Transpolar Drift from October 2019 to October 2020. The campaign documented an annual cycle of physical, biological, and chemical processes impacting the atmosphere-ice-ocean system. Of central importance were measurements of the thermodynamic and dynamic evolution of the sea ice. A multi-agency international team led by the University of Colorado/CIRES and NOAA-PSL observed meteorology and surface-atmosphere energy exchanges, including radiation; turbulent momentum flux; turbulent latent and sensible heat flux; and snow conductive flux. There were four stations on the ice, a 10 m micrometeorological tower paired with a 23/30 m mast and radiation station and three autonomous Atmospheric Surface Flux Stations. Collectively, the four stations acquired ~928 days of data. This manuscript documents the acquisition and post-processing of those measurements and provides a guide for researchers to access and use the data products.

A network analytic investigation of avoidance, dampening, and devaluation of positivity.

BACKGROUND AND OBJECTIVES: Reward Devaluation Theory suggests that devaluation of positivity may be integral in understanding depression (Winer & Salem, 2016). Specifically, the anticipatory (e.g., fear of happiness) and responsive (e.g., dampening) behaviors related to the processing of positivity may play a role in the development and maintenance of depression. METHODS: The goal of this study was to examine the potential overlap between measures that operationalize positivity avoidance, two Fear of Happiness Scales (Gilbert et al., 2012; Joshanloo, 2013), as well as positivity dampening, measured via the dampening subscale of the Responses to Positive Affect Questionnaire (Feldman et al., 2008). Network and community analyses were employed to examine the extent to which the items of these measures clustered into their parent measures and investigate the dynamic interactions between items. RESULTS: The results of the community analysis revealed that the three self-report measures overall clustered into their parent measures, except for the Gilbert et al. (2012) Fear of Happiness Scale, which clustered into two separate communities. The most influential nodes represented the concept that good feelings are often followed by negative outcomes. Additionally, nodes related to the theme of fear of letting oneself become happy emerged as the strongest bridge nodes. LIMITATIONS: One limitation of this study is the use of a cross-sectional design; thus, causality cannot be inferred, but the results can guide future longitudinal network designs. CONCLUSIONS: These findings demonstrate how anticipatory avoidance and responsive dampening may influence depression, thus providing evidence for unique targets for treatment.

Inducible expression of interleukin-12 augments the efficacy of affinity-tuned chimeric antigen receptors in murine solid tumor models.

The limited number of targetable tumor-specific antigens and the immunosuppressive nature of the microenvironment within solid malignancies represent major barriers to the success of chimeric antigen receptor (CAR)-T cell therapies. Here, using epithelial cell adhesion molecule (EpCAM) as a model antigen, we used alanine scanning of the complementarity-determining region to fine-tune CAR affinity. This allowed us to identify CARs that could spare primary epithelial cells while still effectively targeting EpCAMhigh tumors. Although affinity-tuned CARs showed suboptimal antitumor activity in vivo, we found that inducible secretion of interleukin-12 (IL-12), under the control of the NFAT promoter, can restore CAR activity to levels close to that of the parental CAR. This strategy was further validated with another affinity-tuned CAR specific for intercellular adhesion molecule-1 (ICAM-1). Only in affinity-tuned CAR-T cells was NFAT activity stringently controlled and restricted to tumors expressing the antigen of interest at high levels. Our study demonstrates the feasibility of specifically gearing CAR-T cells towards recognition of solid tumors by combining inducible IL-12 expression and affinity-tuned CAR.

Ex vivo expansion of circulating tumour cells (CTCs).

Circulating tumour cells (CTCs) are a critical intermediate step in the process of cancer metastasis. The reliability of CTC isolation/purification has limited both the potential to report on metastatic progression and the development of CTCs as targets for therapeutic intervention. Here we report a new methodology, which optimises the culture conditions for CTCs using primary cancer cells as a model system. We exploited the known biology that CTCs thrive in hypoxic conditions, with their survival and proliferation being reliant on the activation of hypoxia-inducible factor 1 alpha (HIF-1α). We isolated epithelial-like and quasi-mesenchymal CTC phenotypes from the blood of a cancer patient and successfully cultured these cells for more than 8 weeks. The presence of CTC clusters was required to establish and maintain long-term cultures. This novel methodology for the long-term culture of CTCs will aid in the development of downstream applications, including CTC theranostics.

Individuals fearing positivity do not perceive positive affect treatments as strong fits: A novel experimental finding and replication.

BACKGROUND AND OBJECTIVES: Positive affect treatments, which hold great promise to connect with those who are otherwise resistant to depression treatments, attempt to upregulate positive emotions. These treatments have potential advantages over standard therapies because they target cross-diagnostic core symptoms (e.g., anhedonia) that may respond better to interventions aimed at increased positivity. However, the extent to which these treatments are a perceived fit by individuals for whom they were developed (i.e., individuals who are afraid of, avoid, or experience less positivity) is unclear. METHODS: We conducted two independent studies utilizing a cross-sectional, experimental design to examine perceived treatment fit. Participants (Study 1: N = 416; Study 2: N = 321) read counterbalanced treatment descriptions of (1) positive affect treatment and (2) psychodynamic psychotherapy and answered questions regarding perceived treatment fit, effectiveness, and preference of the two treatments. RESULTS: Our findings suggest that individuals fearful of happiness perceived a prospective depression treatment specifically targeting positivity as a poorer fit, demonstrating an opposite pattern to the overall samples' treatment preference in both studies. Thus, as predicted by Reward Devaluation Theory, those fearing positivity exhibited avoidance behaviors for treatments that are to an extent designed, and might otherwise be most effective, for them. LIMITATIONS: The current study utilized a college student sample. CONCLUSION: These empirical findings may ultimately inform psychoeducation of why positive affect treatments, which are in direct contrast with clients' preferences, may be the very treatments they need the most.

Integrating plant physiology into simulation of fire behavior and effects.

Wildfires are a global crisis, but current fire models fail to capture vegetation response to changing climate. With drought and elevated temperature increasing the importance of vegetation dynamics to fire behavior, and the advent of next generation models capable of capturing increasingly complex physical processes, we provide a renewed focus on representation of woody vegetation in fire models. Currently, the most advanced representations of fire behavior and biophysical fire effects are found in distinct classes of fine-scale models and do not capture variation in live fuel (i.e. living plant) properties. We demonstrate that plant water and carbon dynamics, which influence combustion and heat transfer into the plant and often dictate plant survival, provide the mechanistic linkage between fire behavior and effects. Our conceptual framework linking remotely sensed estimates of plant water and carbon to fine-scale models of fire behavior and effects could be a critical first step toward improving the fidelity of the coarse scale models that are now relied upon for global fire forecasting. This process-based approach will be essential to capturing the influence of physiological responses to drought and warming on live fuel conditions, strengthening the science needed to guide fire managers in an uncertain future.

Macular injuries secondary to handheld lasers in a paediatric population-clinical characteristics and indicators of visual impact.

BACKGROUND/OBJECTIVES: Aim to identify incidence and prevalence of laser-induced retinal injuries in the Northern Ireland paediatric population and to determine negative clinical and OCT indicators in relation to visual acuity. SUBJECTS/METHODS: A retrospective analysis was conducted of retinal injuries secondary to handheld laser pens over a 6-year time period with presenting and final visual acuity (VA), laser source and circumstances of the injury recorded. Fundus photographs and OCT images for each case were also collated. RESULTS: Sixty-five patients (74 eyes) were identified of which 72% were male and mean age was 11.6 years. 40% of patients were symptomatic. Mean presenting VA was 0.16 LogMAR. VA was ≤0.30 LogMAR in 20 eyes (27%) at presentation. Features which impacted VA to a significant level were foveolar location, diffuse morphology, ELM and BM/RPE/IDZ disruption and ORH presence on presenting OCT images. ORHs or ELM disruption resulted in a significant risk ratio of 3.5 (p = 0.002) and 3.4 (p = <0.001) respectively. Mean presenting VA was demonstrated to improve during follow-up from 0.36 to 0.22 LogMAR (n = 20, p = 0.03). When VA was ≤0.30 LogMAR at presentation, mean presenting VA improved from 0.56 to 0.29 LogMAR (p < 0.01) with 58% of eyes improving to a VA of better than 0.30 LogMAR. CONCLUSIONS: The overall visual loss from macular laser injuries was low and we have identified features on retinal imaging that significantly impact presenting VA. When VA is affected following macular laser injury there is evidence of recovery with >50% of those presenting with VA ≤ 0.30 LogMAR improving to better than 0.30 LogMAR.

ATTCT and ATTCC repeat expansions in the ATXN10 gene affect disease penetrance of spinocerebellar ataxia type 10.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal-dominant disorder caused by an expanded pentanucleotide repeat in the ATXN10 gene. This repeat expansion, when fully penetrant, has a size of 850-4,500 repeats. It has been shown that the repeat composition can be a modifier of disease, e.g., seizures. Here, we describe a Mexican kindred in which we identified both pure (ATTCT)n and mixed (ATTCT)n-(ATTCC)n expansions in the same family. We used amplification-free targeted sequencing and optical genome mapping to decipher the composition of these repeat expansions. We found a considerable degree of mosaicism of the repeat expansion. This mosaicism was confirmed in skin fibroblasts from individuals with ATXN10 expansions with RNAScope in situ hybridization. All affected family members with the mixed ATXN10 repeat expansion showed typical clinical signs of spinocerebellar ataxia and epilepsy. In contrast, individuals with the pure ATXN10 expansion present with Parkinson's disease or are unaffected, even in individuals more than 20 years older than the average age at onset for SCA10. Our findings suggest that the pure (ATTCT)n expansion is non-pathogenic, while repeat interruptions, e.g., (ATTCC)n, are necessary to cause SCA10. This mechanism has been recently described for several other repeat expansions including SCA31 (BEAN1), SCA37 (DAB1), and three loci for benign adult familial myoclonic epilepsy BAFME (SAMD12, TNRC6A, RAPGEF2). Therefore, long-read sequencing and optical genome mapping of the entire genomic structure of repeat expansions are critical for clinical practice and genetic counseling, as variations in the repeat can affect disease penetrance, symptoms, and disease trajectory.

GPNMB confers risk for Parkinson's disease through interaction with α-synuclein.

Many risk loci for Parkinson's disease (PD) have been identified by genome-wide association studies (GWASs), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel single-nucleotide polymorphism rs199347) to GPNMB through colocalization analyses of expression quantitative trait locus and PD risk signals, confirmed by allele-specific expression studies in the human brain. In cells, glycoprotein nonmetastatic melanoma protein B (GPNMB) coimmunoprecipitated and colocalized with α-synuclein (aSyn). In induced pluripotent stem cell-derived neurons, loss of GPNMB resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology. In 731 PD and 59 control biosamples, GPNMB was elevated in PD plasma, associating with disease severity. Thus, GPNMB represents a PD risk gene with potential for biomarker development and therapeutic targeting.

Insect infestations and the persistence and functioning of oak-pine mixedwood forests in the mid-Atlantic region, USA.

Damage from infestations of Lymantria dispar L. in oak-dominated stands and southern pine beetle (Dendroctonus frontalis Zimmermann) in pine-dominated stands have far exceeded impacts of other disturbances in forests of the mid-Atlantic Coastal Plain over the last two decades. We used forest census data collected in undisturbed and insect-impacted stands combined with eddy covariance measurements made pre- and post-disturbance in oak-, mixed and pine-dominated stands to quantify how these infestations altered forest composition, structure and carbon dynamics in the Pinelands National Reserve of southern New Jersey. In oak-dominated stands, multi-year defoliation during L. dispar infestations resulted in > 40% mortality of oak trees and the release of pine saplings and understory vegetation, while tree mortality was minimal in mixed and pine-dominated stands. In pine-dominated stands, southern pine beetle infestations resulted in > 85% mortality of pine trees but had minimal effect on oaks in upland stands or other hardwoods in lowland stands, and only rarely infested pines in hardwood-dominated stands. Because insect-driven disturbances are both delaying and accelerating succession in stands dominated by a single genus but having less effect in mixed-composition stands, long-term disturbance dynamics are favoring the formation and persistence of uneven age oak-pine mixedwood stands. Changes in forest composition may have little impact on forest productivity and evapotranspiration; although seasonal patterns differ, with highest daily rates of net ecosystem production (NEP) during the growing season occurring in an oak-dominated stand and lowest in a pine-dominated stand, integrated annual rates of NEP are similar among oak-, mixed and pine-dominated stands. Our research documents the formation of mixedwood stands as a consequence of insect infestations in the mid-Atlantic region and suggests that managing for mixedwood stands could reduce damage to forest products and provide greater continuity in ecosystem functioning.

Can restoration of fire-dependent ecosystems reduce ticks and tick-borne disease prevalence in the eastern United States?

Over the past century, fire suppression has facilitated broad ecological changes in the composition, structure, and function of fire-dependent landscapes throughout the eastern US, which are in decline. These changes have likely contributed mechanistically to the enhancement of habitat conditions that favor pathogen-carrying tick species, key wildlife hosts of ticks, and interactions that have fostered pathogen transmission among them and to humans. While the long-running paradigm for limiting human exposure to tick-borne diseases focuses responsibility on individual prevention, the continued expansion of medically important tick populations, increased incidence of tick-borne disease in humans, and emergence of novel tick-borne diseases highlights the need for additional approaches to stem this public health challenge. Another approach that has the potential to be a cost-effective and widely applied but that remains largely overlooked is the use of prescribed fire to ecologically restore degraded landscapes that favor ticks and pathogen transmission. We examine the ecological role of fire and its effects on ticks within the eastern United States, especially examining the life cycles of forest-dwelling ticks, shifts in regional-scale fire use over the past century, and the concept that frequent fire may have helped moderate tick populations and pathogen transmission prior to the so-called fire-suppression era that has characterized the past century. We explore mechanisms of how fire and ecological restoration can reduce ticks, the potential for incorporating the mechanisms into the broader strategy for managing ticks, and the challenges, limitations, and research needs of prescribed burning for tick reduction.

No Evidence of the Vertical Transmission of Non-Virulent Infectious Salmon Anaemia Virus (ISAV-HPR0) in Farmed Atlantic Salmon.

The nonvirulent infectious salmon anaemia virus (ISAV-HPR0) is the putative progenitor for virulent-ISAV, and a potential risk factor for the development of infectious salmon anaemia (ISA). Understanding the transmission dynamics of ISAV-HPR0 is fundamental to proper management and mitigation strategies. Here, we demonstrate that ISAV-HPR0 causes prevalent and transient infections in all three production stages of Atlantic salmon in the Faroe Islands. Phylogenetic analysis of the haemagglutinin-esterase gene from 247 salmon showed a clear geographical structuring into two significantly distinct HPR0-subgroups, which were designated G2 and G4. Whereas G2 and G4 co-circulated in marine farms, Faroese broodfish were predominantly infected by G2, and smolt were predominantly infected by G4. This infection pattern was confirmed by our G2- and G4-specific RT-qPCR assays. Moreover, the HPR0 variants detected in Icelandic and Norwegian broodfish were never detected in the Faroe Islands, despite the extensive import of ova from both countries. Accordingly, the vertical transmission of HPR0 from broodfish to progeny is uncommon. Phylogenetic and statistical analysis suggest that HPR0 persists in the smolt farms as "house-strains", and that new HPR0 variants are occasionally introduced from the marine environment, probably by HPR0-contaminated sea-spray. Thus, high biosecurity-including water and air intake-is required to avoid the introduction of pathogens to the smolt farms.

Genomic Epidemiology of Salmonid Alphavirus in Norwegian Aquaculture Reveals Recent Subtype-2 Transmission Dynamics and Novel Subtype-3 Lineages.

Viral disease poses a major barrier to sustainable aquaculture, with outbreaks causing large economic losses and growing concerns for fish welfare. Genomic epidemiology can support disease control by providing rapid inferences on viral evolution and disease transmission. In this study, genomic epidemiology was used to investigate salmonid alphavirus (SAV), the causative agent of pancreas disease (PD) in Atlantic salmon. Our aim was to reconstruct SAV subtype-2 (SAV2) diversity and transmission dynamics in recent Norwegian aquaculture, including the origin of SAV2 in regions where this subtype is not tolerated under current legislation. Using nanopore sequencing, we captured ~90% of the SAV2 genome for n = 68 field isolates from 10 aquaculture production regions sampled between 2018 and 2020. Using time-calibrated phylogenetics, we infer that, following its introduction to Norway around 2010, SAV2 split into two clades (SAV2a and 2b) around 2013. While co-present at the same sites near the boundary of Møre og Romsdal and Trøndelag, SAV2a and 2b were generally detected in non-overlapping locations at more Southern and Northern latitudes, respectively. We provide evidence for recent SAV2 transmission over large distances, revealing a strong connection between Møre og Romsdal and SAV2 detected in 2019/20 in Rogaland. We also demonstrate separate introductions of SAV2a and 2b outside the SAV2 zone in Sognefjorden (Vestland), connected to samples from Møre og Romsdal and Trøndelag, respectively, and a likely 100 km Northward transmission of SAV2b within Trøndelag. Finally, we recovered genomes of SAV2a and SAV3 co-infecting single fish in Rogaland, involving novel SAV3 lineages that diverged from previously characterized strains >25 years ago. Overall, this study demonstrates useful applications of genomic epidemiology for tracking viral disease spread in aquaculture.

Bellagio II Report: Terrestrial Applications of Space Medicine Research.

AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.