Association of Blood Biomarkers With Acute Sport-Related Concussion in Collegiate Athletes: Findings From the NCAA and Department of Defense CARE Consortium

Importance: There is potential scientific and clinical value in validation of objective biomarkers for sport-related concussion (SRC). Objective: To investigate the association of acute-phase blood biomarker levels with SRC in collegiate athletes. Design, Setting, and Participants: This multicenter, prospective, case-control study was conducted by the National Collegiate Athletic Association (NCAA) and the US Department of Defense Concussion Assessment, Research, and Education (CARE) Consortium from February 20, 2015, to May 31, 2018, at 6 CARE Advanced Research Core sites. A total of 504 collegiate athletes with concussion, contact sport control athletes, and non-contact sport control athletes completed clinical testing and blood collection at preseason baseline, the acute postinjury period, 24 to 48 hours after injury, the point of reporting being asymptomatic, and 7 days after return to play. Data analysis was conducted from March 1 to November 30, 2019. Main Outcomes and Measures: Glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light chain, and tau were quantified using the Quanterix Simoa multiplex assay. Clinical outcome measures included the Sport Concussion Assessment Tool-Third Edition (SCAT-3) symptom evaluation, Standardized Assessment of Concussion, Balance Error Scoring System, and Brief Symptom Inventory 18. Results: A total of 264 athletes with concussion (mean [SD] age, 19.08 [1.24] years; 211 [79.9%] male), 138 contact sport controls (mean [SD] age, 19.03 [1.27] years; 107 [77.5%] male), and 102 non-contact sport controls (mean [SD] age, 19.39 [1.25] years; 82 [80.4%] male) were included in the study. Athletes with concussion had significant elevation in GFAP (mean difference, 0.430 pg/mL; 95% CI, 0.339-0.521 pg/mL; P < .001), UCH-L1 (mean difference, 0.449 pg/mL; 95% CI, 0.167-0.732 pg/mL; P < .001), and tau levels (mean difference, 0.221 pg/mL; 95% CI, 0.046-0.396 pg/mL; P = .004) at the acute postinjury time point compared with preseason baseline. Longitudinally, a significant interaction (group × visit) was found for GFAP (F7,1507.36 = 16.18, P < .001), UCH-L1 (F7,1153.09 = 5.71, P < .001), and tau (F7,1480.55 = 6.81, P < .001); the interaction for neurofilament light chain was not significant (F7,1506.90 = 1.33, P = .23). The area under the curve for the combination of GFAP and UCH-L1 in differentiating athletes with concussion from contact sport controls at the acute postinjury period was 0.71 (95% CI, 0.64-0.78; P < .001); the acute postinjury area under the curve for all 4 biomarkers combined was 0.72 (95% CI, 0.65-0.79; P < .001). Beyond SCAT-3 symptom score, GFAP at the acute postinjury time point was associated with the classification of athletes with concussion from contact controls (β = 12.298; 95% CI, 2.776-54.481; P = .001) and non-contact sport controls (β = 5.438; 95% CI, 1.676-17.645; P = .005). Athletes with concussion with loss of consciousness or posttraumatic amnesia had significantly higher levels of GFAP than athletes with concussion with neither loss of consciousness nor posttraumatic amnesia at the acute postinjury time point (mean difference, 0.583 pg/mL; 95% CI, 0.369-0.797 pg/mL; P < .001). Conclusions and Relevance: The results suggest that blood biomarkers can be used as research tools to inform the underlying pathophysiological mechanism of concussion and provide additional support for future studies to optimize and validate biomarkers for potential clinical use in SRC

Macrophage and neutrophil interactions in the pancreatic tumor microenvironment drive the pathogenesis of pancreatic cancer

Despite modest improvements in survival in recent years, pancreatic adenocarcinoma remains a deadly disease with a 5-year survival rate of only 9%. These poor outcomes are driven by failure of early detection, treatment resistance, and propensity for early metastatic spread. Uncovering innovative therapeutic modalities to target the resistance mechanisms that make pancreatic cancer largely incurable are urgently needed. In this review, we discuss the immune composition of pancreatic tumors, including the counterintuitive fact that there is a significant inflammatory immune infiltrate in pancreatic cancer yet anti-tumor mechanisms are subverted and immune behaviors are suppressed. Here, we emphasize how immune cell interactions generate tumor progression and treatment resistance. We narrow in on tumor macrophage (TAM) spatial arrangement, polarity/function, recruitment, and origin to introduce a concept where interactions with tumor neutrophils (TAN) perpetuate the microenvironment. The sequelae of macrophage and neutrophil activities contributes to tumor remodeling, fibrosis, hypoxia, and progression. We also discuss immune mechanisms driving resistance to standard of care modalities. Finally, we describe a cadre of treatment targets, including those intended to overcome TAM and TAN recruitment and function, to circumvent barriers presented by immune infiltration in pancreatic adenocarcinoma

Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized pp++AA collisions at sNN=200\sqrt{s_{_{NN}}}=200 GeV

During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized $p$$+$$p$ collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in $p$$+$$p$ collisions predicts only a moderate atomic-mass-number ($A$) dependence. In contrast, the asymmetries observed at RHIC in $p$$+$$A$ collisions showed a surprisingly strong $A$ dependence in inclusive forward neutron production. The observed asymmetry in $p$$+$Al collisions is much smaller, while the asymmetry in $p$$+$Au collisions is a factor of three larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed $A$ dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for publication in Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

L\'evy-stable two-pion Bose-Einstein correlations in sNN=200\sqrt{s_{_{NN}}}=200 GeV Au++Au collisions

We present a detailed measurement of charged two-pion correlation functions in 0%-30% centrality $\sqrt{s_{_{NN}}}=200$ GeV Au$+$Au collisions by the PHENIX experiment at the Relativistic Heavy Ion Collider. The data are well described by Bose-Einstein correlation functions stemming from L\'evy-stable source distributions. Using a fine transverse momentum binning, we extract the correlation strength parameter $\lambda$, the L\'evy index of stability $\alpha$ and the L\'evy length scale parameter $R$ as a function of average transverse mass of the pair $m_T$. We find that the positively and the negatively charged pion pairs yield consistent results, and their correlation functions are represented, within uncertainties, by the same L\'evy-stable source functions. The $\lambda(m_T)$ measurements indicate a decrease of the strength of the correlations at low $m_T$. The L\'evy length scale parameter $R(m_T)$ decreases with increasing $m_T$, following a hydrodynamically predicted type of scaling behavior. The values of the L\'evy index of stability $\alpha$ are found to be significantly lower than the Gaussian case of $\alpha=2$, but also significantly larger than the conjectured value that may characterize the critical point of a second-order quark-hadron phase transition.Comment: 448 authors, 25 pages, 11 figures, 4 tables, 2010 data. v2 is version accepted for publication in Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm