Study Design-Prospective case seriesObjective-Evaluate lumbar paraspinal muscle (PSM) cross-sectional area and intervertebral disc (IVD) height changes induced by a 6-month space mission on the International Space Station (ISS). The long-term objective of this project is to promote spine health and prevent spinal injury during space missions as well as here on Earth.Summary of Background-NASA crewmembers have a 4.3 times higher risk of herniated IVDs, compared to the general and military aviator populations. The highest risk occurs during the first year after a mission. Microgravity exposure during long-duration spaceflights results in ~5cm lengthening of body height, spinal pain, and skeletal deconditioning. How the PSMs and IVDs respond during spaceflight is not well described.Methods-Six NASA crewmembers were imaged supine with a 3T MRI. Imaging was conducted pre-flight, immediately post-flight and then 33 to 67 days after landing. Functional cross-sectional area (FCSA) measurements of the PSMs were performed at the L3-4 level. FCSA was measured by grayscale thresholding within the posterior lumbar extensors to isolate lean muscle on T2-weighted scans. IVD heights were measured at the anterior, middle and posterior sections of all lumbar levels. Repeated measures ANOVA was used to determine significance at p<0.05, followed by post-hoc testing.Results-Paraspinal lean muscle mass, as indicated by the FCSA, decreased from 86% of the total PSM cross-sectional area down to 72%, immediately after the mission. Recovery of 68% of HHS Public AccessAuthor manuscript Spine (Phila Pa 1976 Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript the post-flight loss occurred over the next 6 weeks, still leaving a significantly lower lean muscle fractional content compared to pre-flight values. In contrast, lumbar IVD heights were not appreciably different at any time point.Conclusions-The data reveal lumbar spine PSM atrophy after long-duration spaceflight. Some FCSA recovery was seen with 46 days post-flight in a terrestrial environment, but it remained incomplete compared to pre-flight levels.

Analysis of the extracts of male ants of Monomorium minimum and M. ebeninum, by GC-MS and GC-FTIR revealed the presence of tyramides 2 and 4c, for which the structures were established by comparison with synthetic samples. These compounds and their analogs 1 and 3 were also found in males of other Monomorium species, males of Myrmicaria opaciventris, and males of several Solenopsis (Diplorhoptrum) species. Vapor-phase FTIR spectra revealed critically important structural clues to two of the tyramides, which had methyl-branching in the tyramide acyl moiety. Tyramide 4c exhibited a strong intramolecular amide NH hydrogen bond where an α-keto group was deduced to be present in the acyl moiety and also showed the overlap of this ketone group frequency with that of the amide νC=O. The biological function of these compounds is uncertain; however their role in ant-mating behavior may be suggested by a large body of evidence.

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SHORT COMUNICATIONThe chemical defense of the Texas cave harvestman Chinquipellobumis madlaei first report on the family Stygnopsidae and on a North American troglobiont harvestman (Opilones: Gonyleptoidea) William A.

433 Background: PD-L1 immunohistochemistry and an 18-gene T cell–inflamed gene expression profile (GEP) are associated with response to anti–PD-1/PD-L1 therapy across tumor types, including urothelial carcinoma. A gene expression signature representing convergent biology related to stromal/EMT/TGF-β pathways was developed and prespecified for testing for association with pembrolizumab response in urothelial carcinoma patients treated on the KEYNOTE-052 trial (NCT02335424). Methods: KEYNOTE-052 was a single-arm phase 2 trial of pembrolizumab in cisplatin-ineligible patients with previously untreated, advanced urothelial carcinoma. Primary objective of this analysis was to assess the association between the Stromal/EMT/TGF-β signature and outcomes (best overall response [BOR], PFS, OS) as an independent biomarker and to understand its potential prognostic/predictive role beyond the T cell–inflamed GEP score or PD-L1 assessed using combined positive score (CPS). Cox regression models for PFS and OS and a logistic regression model for BOR evaluated associations between Stromal/EMT/TGF-β signature and outcomes adjusting for ECOG performance status (PS) and level of the GEP or CPS (1-sided P value). Results: RNA-Seq data from baseline tumor specimens were available for 187/370 patients on KEYNOTE-052. Lower Stromal/EMT/TGF-β score was associated with favorable BOR rate ( P < 0.001), PFS ( P < 0.001), and OS ( P = 0.002) after adjustment for ECOG PS and GEP (which remained significant at the 0.05 level in all cases). The patterns indicated a very consistent downward trend in the distribution of the Stromal/EMT/TGF-β score for responders versus nonresponders, regardless of GEP. In models that adjusted for both ECOG PS and PD-L1 CPS, the Stromal/EMT/TGF-β score remained significant (BOR rate, P = 0.002; PFS, P = 0.013; OS, P = 0.029). Conclusions: Higher Stromal/EMT/TGF-β signature was associated with resistance to pembrolizumab independently of GEP or PD-L1 in urothelial carcinoma patients on the KEYNOTE-052 trial. Clinical trial information: NCT02335424.

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Background: L + P had antitumor activity and a manageable safety profile in previously treated advanced EC in KEYNOTE-146/study 111 (NCT02501096). In this exploratory analysis, we evaluated the association between gene expression signatures and tumor mutational burden (TMB) and clinical outcomes.

TPS9117 Background: Pembrolizumab-based combination immunotherapy aims to improve clinical outcomes over pembrolizumab monotherapy. A biomarker-based therapeutic approach may be associated with improved response to different combination therapies of immune checkpoint inhibitors and may improve overall outcomes in NSCLC. The randomized, multicenter, open-label, phase 2 KEYNOTE-495 trial ( NCT03516981 ) will evaluate the clinical usefulness of biomarker-informed, pembrolizumab-based combination therapy in patients with treatment-naive, advanced NSCLC. Methods: This is a group-sequential, adaptive randomization trial. Patients will have histologically or cytologically confirmed treatment-naive, advanced NSCLC, documented absence of EGFR and B-Raf mutations and ALK and ROS1 gene rearrangements, measurable disease per RECIST v1.1, and ECOG PS 0-1. Tumor tissue from patients will be initially screened for 2 validated, independent, next-generation biomarkers: T cell–inflamed gene expression profile (GEP) and tumor mutational burden (TMB). Based on results of biomarker screening, patients will be assigned to 1 of 4 groups: TMBlowGEPlow, TMBhighGEPlow, TMBlowGEPhigh, and TMBhighGEPhigh. Within each group, patients will be randomly assigned to receive pembrolizumab 200 mg Q3W intravenously (IV) combined with either MK-4280 200 mg Q3W (anti–LAG-3) IV or lenvatinib 20 mg orally once daily, with the randomization assignment adaptively modified based on interim efficacy analyses. Response will be assessed by imaging every 9 weeks for the first year and every 12 weeks thereafter using RECIST v1.1. Treatment will continue for 35 cycles (~2 years). Patients in the pembrolizumab + lenvatinib arm who complete 35 treatments may continue with lenvatinib monotherapy until disease progression or toxicity. Treatment arms may be terminated during the interim analysis due to safety, prespecified futility criteria, or both. Primary end point is investigator-assessed objective response rate (RECIST v1.1). Secondary end points are progression-free survival, overall survival, and safety. Recruitment and screening are ongoing in more than 8 countries. Clinical trial information: NCT03516981.