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While primary bone malignancies make up just 0.2% of all cancers, osteosarcoma (OS) is the third most common cancer in adolescents. Due to its highly complex and heterogeneous tumor microenvironment (TME), OS has proven difficult to treat. There has been little to no improvement in therapy for this disease over the last 40 years. Even the recent success of immunotherapies in other blood-borne and solid malignancies has not translated to OS. With frequent recurrence and lung metastases continuing to pose a challenge in the clinic, recent advancements in molecular profiling, such as single-cell RNA sequencing (scRNA-seq), have proven useful in identifying novel biomarkers of OS tumors while providing new insight into this TME that could potentially lead to new therapeutic options. This review combines the analyses of over 150,000 cells from 18 lesions ranging from primary, recurrent, and metastatic OS lesions, revealing distinct cellular populations and gene signatures that exist between them. Here, we detail these previous findings and ultimately convey the intratumoral heterogeneity that exists within OS tumor specimens., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Objective: To determine whether serum fructosamine correlates with glycemic control and clinical outcomes in patients being screened for cystic fibrosis-related diabetes (CFRD)., Methods: Fructosamine and percent predicted forced expiratory volume in 1s (FEV 1 ) were measured in patients undergoing a 2h oral glucose tolerance test (OGTT) for CFRD screening. Fractional serum fructosamine (FSF) was calculated as fructosamine/total protein., Results: FSF exhibited a positive correlation with 2h OGTT results (r 2 =0.3201, p=0.009), and ROC curve analysis suggested that FSF can identify patients with an abnormal OGTT (AUC=0.840, p=0.0002). FSF also exhibited a negative correlation with FEV 1 (r 2 =0.3732, p=0.035). Patients with FSF≥3.70μmol/g had significantly lower FEV 1 (median 47%) compared to those with FSF<3.70μmol/g (median 90%; p=0.015)., Conclusions: FSF correlated with both OGTT results and FEV 1 , and reliably identified patients with abnormal OGTT results. This simple blood test shows potential as an effective tool in CFRD screening., (Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: HbA1c is used in the diagnosis and monitoring of diabetes mellitus (DM). Interference from hemoglobin variants is a well-described phenomenon, particularly with HPLC-based methods. While immunoassays may generate more reliable HbA1c results in the presence of some variants, these methods are susceptible to negative interference from high concentrations of HbF. We report a case where an accurate HbA1c result could not be obtained by any available method due to the presence of a compound hemoglobinopathy., Methods: HbA1c was measured by HPLC, immunoassay, and capillary electrophoresis. Hemoglobinopathy investigation consisted of a CBC, hemoglobin fractionation by HPLC and electrophoresis, and molecular analysis., Results: HbA1c analysis by HPLC and capillary electrophoresis gave no result. Analysis by immunoassay yielded HbA1c results of 5.9% (Siemens DCA 2000+) and 5.1% (Roche Integra), which were inconsistent with other markers of glycemic control. Hemoglobinopathy investigation showed HbC with the hereditary persistence of fetal hemoglobin-2 Ghana deletion., Conclusion: Reliable HbA1c results may be unobtainable in the presence of some hemoglobinopathies. HPLC and capillary electrophoresis alerted the laboratory to the presence of an unusual hemoglobinopathy. Immunoassays generated falsely low results without warning, which could lead to missed diagnoses and under treatment of patients with DM., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Protein arginine methylation is one of the epigenetic modifications to proteins that is studied in yeast and is known to be involved in a number of human diseases. All eukaryotes produce Nη-monomethylarginine (ηMMA), asymmetric Nη1, Nη1-dimethylarginine (aDMA), and most produce symmetric Nη1, Nη2-dimethylarginine (sDMA) on proteins, but only yeast produce Nδ-monomethylarginine (δMMA). It has proven difficult to differentiate among all of these methylarginines using mass spectrometry. Accordingly, we demonstrated that the two forms of MMA have indistinguishable primary product ion spectra. However, the secondary product ion spectra of δMMA and ηMMA exhibited distinct patterns of ions. Using incorporation of deuterated methyl-groups in yeast, we determined which secondary product ions were methylated and their structures. Utilizing distinct secondary product ions, a triple quadrupole multiple reaction monitoring cubed (MRM(3)) assay was developed to measure δMMA, ηMMA, sDMA and aDMA derived from hydrolyzed protein. As a proof-of-concept, δMMA and ηMMA were measured using the MRM(3) method in wild type and mutant strains of Saccharomyces cerevisiae and compared to the total MMA measured using an existing assay. The MRM(3) assay represents the only method to directly quantify δMMA and the only method to simultaneously quantify all yeast methylarginines., (Copyright © 2013 Elsevier B.V. All rights reserved.)