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BackgroundFemale youth ice hockey players are an understudied population. This study documented injury types, rates and mechanisms for female youth ice hockey players reporting to US emergency departments to inform safety measures and sideline medical preparedness.MethodsThe National Electronic Injury Surveillance System (NEISS) database was queried for all ice hockey injuries (product code 1279) from January 1, 2002 to December 31, 2019. Cases involving players over the age of 18 years and males were excluded. Incidence rate ratios (IRR) were calculated using OpenEpi and compared between age divisions. Spearman's rank correlation was utilized to evaluate the correlation between age and injury incidence. USA Hockey membership statistics were used to establish the population at risk and calculate incidence rates (IR).ResultsAn estimated 20,384 ice hockey injuries presented to participating United States emergency departments. The number of female youth ice hockey players increased significantly from 36,258 in mechanism on injury. Hopefully this study informs players, parents, coaches, trainers and clinicians about the impact of player-to-player collisions on overall injury burden in the older age divisions of youth female hockey.The rise of antibodies as a promising and rapidly growing class of biotherapeutic proteins has motivated numerous studies to characterize and understand antibody structures. In the past decades, the number of antibody crystal structures increased substantially, which revolutionized the atomistic understanding of antibody functions. Even though numerous static structures are known, various biophysical properties of antibodies (i.e., specificity, hydrophobicity and stability) are governed by their dynamic character. Additionally, the importance of high-quality structures in structure-function relationship studies has substantially increased. These structure-function relationship studies have also created a demand for precise homology models of antibody structures, which allow rational antibody design and engineering when no crystal structure is available. Here, we discuss various aspects and challenges in antibody design and extend the paradigm of describing antibodies with only a single static structure to characterizing them as dynamic ensembles in solution.Objective We aimed to investigate the roles of inflammatory parameters, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and C-reactive protein/albumin ratio (CAR), in predicting disease recurrence in patients with stage IIA (T3N0M0) high microsatellite instability and microsatellite-stable colon cancer who had no risk factors associated with relapse.Materials and methods We evaluated 155 patients with colon cancer followed in 3 hospitals in Turkey between February 2009 and March 2020. These patients had stage IIA disease and had no risk factors associated with relapse. None of the patients received adjuvant chemotherapy. NLR, PLR, LMR, and CAR parameters were retrospectively obtained from laboratory results at the time of diagnosis, and their associations with disease recurrence were assessed.Results Over a median follow-up period of 38 months (range 4-98 months), 11 of the 155 patients experienced relapse or developed metastases. Multivariate Cox analyses revealed that NLRs of ≥3.12 (hazard ratio [HR] 0.041, 95% confidence interval [CI] 0.048-0.826, p = 0.006) and CARs of ≥0.027 (HR 0.199, 95% CI 0.004-0.404, p = 0.026) were independent prognostic markers predicting relapse. The median 5-year recurrence-free survival rate of patients with NLRs of ≥3.12 at the time of diagnosis was 88.0%; this rate was 100% in patients with NLRs of less then 3.12 (p less then 0.001). Similarly, the median 5-year recurrence-free survival rate of patients with CARs of ≥0.027 at the time of diagnosis was 84.7%; this rate was 95.7% in patients with CARs of less then 0.027 (p = 0.016).Conclusion In this study, NLR and CAR were found to be independent prognostic markers predicting disease recurrence in patients with stage IIA colon cancer who did not receive adjuvant chemotherapy due to low clinical risk.Therapeutic immunoglobulin G (IgG) antibodies have comparatively long half-lives because the neonatal Fc receptor (FcRn) binds to the IgG Fc at acidic pH in the endosome and protects IgG from degradation. To further prolong the half-lives, amino acid-substituted antibodies having high affinity to FcRn are being developed, and one such therapeutic antibody (ravulizumab) has been approved. In this study, we investigated the binding property to FcγR and the conformation of seven FcRn affinity-modulated adalimumab variants to clarify the impact of the amino acid substitutions on the function and conformation of IgG Fc. The amino acid substitutions in T254-P261 caused a change in deuterium uptake into some regions of Fc in HDX-MS analysis, but those at T311, M432 and N438 did not cause such a change. The conformations around F245-L255 (FLFPPKPKDTL) were particularly influenced by the amino acid substitution in M256-P261, and the conformational changes of this region were correlated with the decrease of the affinity to FcγRIIIa. Additionally, we investigated the conformational difference of Fc between a Fc fusion protein (etanercept) and a native IgG (adalimumab). Although the Fc fusion proteins were expected to have similar FcRn affinity to IgGs, the affinity of etanercept to FcRn was lower than that of adalimumab, and its half-life was shorter than those of the IgG antibodies. Differences in deuterium uptakes were observed in the two regions where they were also detected in the adalimumab variants, and the conformational differences appeared to be an important factor for the low FcRn affinity of etanercept.Inhibitors of COMT are clinically used for the treatment of Parkinson's disease. Here, we report the first natural pentacyclic triterpenoid-type COMT inhibitors and their structure-activity relationships and inhibition mechanism. selleck compound The most potent compounds were found to be oleanic acid, betulinic acid and celastrol with IC50 values of 3.89-5.07 μM, that acted as mixed (uncompetitive plus non-competitive) inhibitors of COMT, representing a new skeleton of COMT inhibitor. Molecular docking suggested that they can specifically recognise and bind with the unique hydrophobic residues surrounding the catechol pocket. Furthermore, oleanic acid and betulinic acid proved to be less disruptive of mitochondrial membrane potential (MMP) compared to tolcapone, thus reducing the risk of liver toxicity. These findings could be used to produce an ideal lead compound and to guide synthetic efforts in generating related derivatives for further preclinical testing.