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Introduction: As the popularity of ultramarathon participation increases, there still exists a lack of understanding of the unique psychological characteristics of ultramarathon runners. The current study sought to investigate some of the psychological and behavioral factors that are involved in ultramarathon running.Methods: We obtained information from participants of the Bear Chase Trail Race via an online survey. This race is a single-day, multidistance race consisting of a 10 k, half marathon, 50 k, 50 mi, and 100 k run in Lakewood, Colorado, at a base altitude of 1680 m with total altitude in climbs ranging from 663 to 2591 m. We correlated information from the Exercise Addiction Inventory and the Patient Health Questionnaire-2 and demographic information with race finish times.Results: Out of 200 runners who started the race, 98 (48%) completed the survey. Over half of the runners were men (61.2%), and the average age was 39.0 years (SD±8.9; range 21-64 years). A number of respondents (20%) screened positive for exercise addiction concerns. Approximately 20% of our sample screened positive for depressive symptoms (Patient Health Questionnaire-2 score >3). The majority of participants reported receiving strong social support from current partners with regard to their ultramarathon running training time and goals.Conclusions: Although only a screening, the number of positive screens on the Exercise Addiction Inventory suggests use of screening measures with an ultramarathon running population. Athletes with positive screening tests should be fully evaluated for depression and exercise addiction because this would enable appropriate athlete support and treatment referral. [ABSTRACT FROM AUTHOR]

The highly lethal brain cancer glioblastoma (GBM) poses a daunting challenge because the blood-brain barrier renders potentially druggable amplified or mutated oncoproteins relatively inaccessible. Here, we identify sphingomyelin phosphodiesterase 1 (SMPD1), an enzyme that regulates the conversion of sphingomyelin to ceramide, as an actionable drug target in GBM. We show that the highly brain-penetrant antidepressant fluoxetine potently inhibits SMPD1 activity, killing GBMs, through inhibition of epidermal growth factor receptor (EGFR) signaling and via activation of lysosomal stress. Combining fluoxetine with temozolomide, a standard of care for GBM, causes massive increases in GBM cell death and complete tumor regression in mice. Incorporation of real-world evidence from electronic medical records from insurance databases reveals significantly increased survival in GBM patients treated with fluoxetine, which was not seen in patients treated with other selective serotonin reuptake inhibitor (SSRI) antidepressants. These results nominate the repurposing of fluoxetine as a potentially safe and promising therapy for patients with GBM and suggest prospective randomized clinical trials. [Display omitted] • The unique membrane lipid composition makes GBMs sensitive to SMPD1 inhibition • Fluoxetine inhibits SMPD1, sphingomyelin metabolism, and EGFR signaling in GBM • Fluoxetine safely and potently shrinks GBM tumors and prevents recurrence in mice • Addition of fluoxetine to standard-of-care chemotherapy improves patient survival Bi et al. reveal an actionable lipid vulnerability in GBM that can be exploited with a safe, highly brain-penetrant, FDA-approved drug. They show that fluoxetine kills GBMs by blocking acid sphingomyelinase, and they demonstrate that, when added to standard of care, fluoxetine, unlike other SSRIs, significantly improves patient survival. [ABSTRACT FROM AUTHOR]

Advances in DNA sequencing technologies have reshaped our understanding of the molecular basis of cancer, providing a precise genomic view of tumors. Complementary biochemical and biophysical perspectives of cancer point toward profound shifts in nutrient uptake and utilization that propel tumor growth and major changes in the structure of the plasma membrane of tumor cells. The molecular mechanisms that bridge these fundamental aspects of tumor biology remain poorly understood. Here, we show that the lysophosphatidylcholine acyltransferase LPCAT1 functionally links specific genetic alterations in cancer with aberrant metabolism and plasma membrane remodeling to drive tumor growth. Growth factor receptor-driven cancers are found to depend on LPCAT1 to shape plasma membrane composition through enhanced saturated phosphatidylcholine content that is, in turn, required for the transduction of oncogenic signals. These results point to a genotype-informed strategy that prioritizes lipid remodeling pathways as therapeutic targets for diverse cancers. • Persistent EGFR signaling activates membrane lipid remodeling through LPCAT1 • LPCAT1 regulates phospholipid saturation and oncogenic growth factor signaling • LPCAT1 is frequently amplified in cancer and associated with poor patient survival • Membrane phospholipid remodeling generates an actionable dependency across cancers Persistent growth factor receptor signaling and metabolic reprograming are hallmarks of cancer. Bi et al. show that LPCAT1-mediated phospholipid remodeling supports the sustained oncogenic activity of growth factor receptors on plasma membrane of tumor cells, suggesting an actionable dependency in a wide variety of cancers. [ABSTRACT FROM AUTHOR]

Hydrogen can be a critical part of the energy transition and salt caverns have been considered for underground hydrogen storage. Although there have been some successful experiences of hydrogen storage in salt caverns in Europe and the United States, it is essential to exercise caution when selecting caverns for storage to ensure safe operations. This study investigates the relationship between rock heterogeneity and helium diffusion by testing salt-rock cores from the Lotsberg Formation, Alberta, Canada. We characterized salt rock heterogeneity by analyzing the results of X-ray diffraction (XRD) analysis, thin-section microscopy, scanning electron microscopy/energy dispersive X-ray spectrometry (SEM/EDS), and high-resolution CT scans. Then, diffusion tests were conducted using a custom-designed HPHT visualization cell on core samples with different compositions and crystal sizes. The samples in this study were categorized as Lotsberg Salt and Lotsberg Marlstone. Lotsberg Salt mainly consisted of halite with trace amounts of carbonate impurities, while Lotsberg Marlstone comprised halite with a carbonate matrix containing carbonates, clays, quartz, and muscovite. Helium diffusion through pure and intact halite crystals was negligible, and the micro-scale halite crystal boundaries are non-open or poorly unconnected for helium diffusion. Halite samples with macro-scale grain boundaries and carbonate impurities exhibited more interconnected pore networks, resulting in increased rates of helium diffusion. However, the formation of secondary halite veins between grain boundaries can lead to tightly sealed boundaries that have poor connectivity, limiting helium diffusion within the sample. Salt-rock cores with intergranular fractures and unsealed grain boundaries showed accelerated pressure declines, attributed to the preferential diffusion of helium through these fracture and crack pathways. • Gas transport into salt rocks depends on mineralogy, crystal shape and size. • Gas diffusion through intact halite crystals with no discontinuities is negligible. • Salt crystal boundaries and fractures within grains can be the preferential flow paths for Gas diffusion. [ABSTRACT FROM AUTHOR]

Background In the United States, vaccines have eliminated wild poliovirus (WPV) infection, though resettling refugees may lack immunity and importation of WPV remains a concern. Methods A cross-sectional survey was performed to determine the prevalence of poliovirus immunity in adult refugees resettling in Boise, Idaho, U.S.A.; immunity was evaluated using two definitions: serotypes 1, 2 and 3 positive, or serotypes 1 and 3 positive. Results This survey evaluated 795 adult refugees between August 2010 and November 2012. Poliovirus immunity in adults >18 years was 55.3% for serotypes 1, 2 and 3 combined, and 60% for serotypes 1 and 3 only. Conclusion This study demonstrated a WPV immunity rate of <60% in a recently resettled adult refugee population in the United States, reinforcing the need to ensure poliovirus immunity in all newly arrived adult refugees, either by expanding pre-departure immunization or by screening for immunity at resettlement and vaccinating when indicated. [ABSTRACT FROM AUTHOR]