Stage related metabolic profile of the synovial fluid in patients with acute flares of knee osteoarthritis.

Background and aim: Osteoarthritis (OA) is the most common joint condition and the leading cause of pain and disability in elderly patients. Currently, there is no biomarker available for the early diagnosis of OA, and limited data is available regarding the molecular basis of progression for OA. For this reason, this study aimed to identify the metabolomic profile of early and late OA using high-performance liquid chromatography coupled with untargeted mass spectrometry (LC-MS). Methods: 31 patients with knee OA and joint effusion were enrolled. Based on Kellgren/Laurence scale, 12 patients were classified as early OA (eOA) and 19 as late OA (lOA). The synovial fluid (SF) was collected and characterized by untargeted LC-MS. Only the metabolites identified in more than 25% of each group were kept for further analysis. Principal component analysis (PCA) enabled the unsupervised clustering of the eOA and lOA groups. Further, for classification, the best three principal components (PCs) were used as input for two machine learning algorithms (random forest and naïve Bayes), which were trained to discriminate between the eOA and lOA groups. Results: 43 metabolites were identified in both eOA and lOA, but after selecting the metabolites present in at least 25% of the patients in each group, the metabolomics analysis yielded a panel of only nine metabolites: four metabolites related to phospholipids (phosphatidylcholine 20:0/18:2 and 18:0/20:2, sphingomyelin, and ceramide), three metabolites belonging to purine metabolites (inosine 5'-phosphate, adenosine thiamine diphosphate, and diadenosine 5',5'-diphosphate), one metabolite was a gonadal steroid hormone (estrone 3-sulfate), and one metabolite represented by heme, with all but ceramide (d18:1/20:0) being enriched in the lOA group. By using as features the best three PCs (PC2, PC8 and PC9), random forest and naïve Bayes machine learning algorithms yielded a classification accuracy of 0.81 and 0.78, respectively. Conclusion: Our LC-MS analysis of SF from patients with eOA and lOA indicates stage-dependent differences, lOA being associated with a perturbed metabolome of phospholipids, purine metabolites, gonadal steroid hormones (estrone 3-sulfate) and a heme molecule. Specific questions need to be answered regarding the biosynthesis and function of these metabolites in osteoarthritic joints, with the aim of developing new relevant biomarkers and therapeutic strategies.

Combined miRNA and SERS urine liquid biopsy for the point-of-care diagnosis and molecular stratification of bladder cancer.

BACKGROUND: Bladder cancer (BC) has the highest per-patient cost of all cancer types. Hence, we aim to develop a non-invasive, point-of-care tool for the diagnostic and molecular stratification of patients with BC based on combined microRNAs (miRNAs) and surface-enhanced Raman spectroscopy (SERS) profiling of urine. METHODS: Next-generation sequencing of the whole miRNome and SERS profiling were performed on urine samples collected from 15 patients with BC and 16 control subjects (CTRLs). A retrospective cohort (BC = 66 and CTRL = 50) and RT-qPCR were used to confirm the selected differently expressed miRNAs. Diagnostic accuracy was assessed using machine learning algorithms (logistic regression, naïve Bayes, and random forest), which were trained to discriminate between BC and CTRL, using as input either miRNAs, SERS, or both. The molecular stratification of BC based on miRNA and SERS profiling was performed to discriminate between high-grade and low-grade tumors and between luminal and basal types. RESULTS: Combining SERS data with three differentially expressed miRNAs (miR-34a-5p, miR-205-3p, miR-210-3p) yielded an Area Under the Curve (AUC) of 0.92 ± 0.06 in discriminating between BC and CTRL, an accuracy which was superior either to miRNAs (AUC = 0.84 ± 0.03) or SERS data (AUC = 0.84 ± 0.05) individually. When evaluating the classification accuracy for luminal and basal BC, the combination of miRNAs and SERS profiling averaged an AUC of 0.95 ± 0.03 across the three machine learning algorithms, again better than miRNA (AUC = 0.89 ± 0.04) or SERS (AUC = 0.92 ± 0.05) individually, although SERS alone performed better in terms of classification accuracy. CONCLUSION: miRNA profiling synergizes with SERS profiling for point-of-care diagnostic and molecular stratification of BC. By combining the two liquid biopsy methods, a clinically relevant tool that can aid BC patients is envisaged.

Cognitive and academic growth among emergent bilingual children at risk and not at risk for math difficulties.

One purpose of this study was to identify cognitive processes within the English (second language [L2]) and Spanish (first language [L1]) language systems that underlie growth in math problem solving among emergent bilingual (EB) children with and without math difficulties (MD). A second purpose was to determine those L1 cognitive processes that play an essential role in predicting math word-problem-solving difficulties. To this end, children (N = 275; children with MD = 90) in Grades 1, 2, and 3 at Wave 1 were administered a battery of math, reading, vocabulary, and cognitive (short-term memory [STM], working memory [WM], rapid naming, and inhibition) measures. The battery of tests was administered again 1 year and 2 years later to the same participants. Three findings were important. First, multilevel logistic modeling suggested that the log-odds of identifying children with MD were best captured by the level of performance on measures of fluid intelligence, Spanish STM, and English WM. Second, the log-odds of identifying children with MD were uniquely related to growth on WM, computation, and number magnitude judgment measures. Finally, the level of performance on L1 measures of reading, calculation, and naming speed and inhibition facilitated the identification of children with MD. In contrast, growth on all Spanish measures, except vocabulary and estimation, increased the log-odds of identifying children with MD. In general, the results suggest that there are constraints or inefficiencies in cognitive processes within and across both language systems that underlie the development of EB children's MD. The results highlight the importance of the phonological and executive systems of WM as important predictors of EB children's math problem-solving difficulties.

SERS Liquid Biopsy Profiling of Serum for the Diagnosis of Kidney Cancer.

Renal cancer (RC) represents 3% of all cancers, with a 2% annual increase in incidence worldwide, opening the discussion about the need for screening. However, no established screening tool currently exists for RC. To tackle this issue, we assessed surface-enhanced Raman scattering (SERS) profiling of serum as a liquid biopsy strategy to detect renal cell carcinoma (RCC), the most prevalent histologic subtype of RC. Thus, serum samples were collected from 23 patients with RCC and 27 controls (CTRL) presenting with a benign urological pathology such as lithiasis or benign prostatic hypertrophy. SERS profiling of deproteinized serum yielded SERS band spectra attributed mainly to purine metabolites, which exhibited higher intensities in the RCC group, and Raman bands of carotenoids, which exhibited lower intensities in the RCC group. Principal component analysis (PCA) of the SERS spectra showed a tendency for the unsupervised clustering of the two groups. Next, three machine learning algorithms (random forest, kNN, naïve Bayes) were implemented as supervised classification algorithms for achieving discrimination between the RCC and CTRL groups, yielding an AUC of 0.78 for random forest, 0.78 for kNN, and 0.76 for naïve Bayes (average AUC 0.77 ± 0.01). The present study highlights the potential of SERS liquid biopsy as a diagnostic and screening strategy for RCC. Further studies involving large cohorts and other urologic malignancies as controls are needed to validate the proposed SERS approach.

SERS liquid biopsy in breast cancer. What can we learn from SERS on serum and urine?

SERS analysis of biofluids, coupled with classification algorithms, has recently emerged as a candidate for point-of-care medical diagnosis. Nonetheless, despite the impressive results reported in the literature, there are still gaps in our knowledge of the biochemical information provided by the SERS analysis of biofluids. Therefore, by a critical assignment of the SERS bands, our work aims to provide a systematic analysis of the molecular information that can be achieved from the SERS analysis of serum and urine obtained from breast cancer patients and controls. Further, we compared the relative performance of five different machine learning algorithms for breast cancer and control samples classification based on the serum and urine SERS datasets, and found comparable classification accuracies in the range of 61-89%. This result is not surprising since both biofluids show striking similarities in their SERS spectra providing similar metabolic information, related to purine metabolites. Lastly, by carefully comparing the two datasets (i.e., serum and urine) we show that it is possible to link the misclassified samples to specific metabolic imbalances, such as carotenoid levels, or variations in the creatinine concentration.

SERS-based DNA methylation profiling allows the differential diagnosis of malignant lymphadenopathy.

This study highlights the potential of surface-enhanced Raman scattering (SERS) to differentiate between B-cell lymphoma (BCL), T-cell lymphoma (TCL), lymph node metastasis of melanoma (Met) and control (Ctr) samples based on the specific SERS signal of DNA extracted from lymph node tissue biopsy. Differences in the methylation profiles as well as the specific interaction of malignant and non-malignant DNA with the metal nanostructure are captured in specific variations of the band at 1005 cm-1, attributed to 5-methylcytosine and the band at 730 cm-1, attributed to adenine. Thus, using the area ratio of these two SERS marker bands as input for univariate classification, an area under the curve (AUC) of 0.70 was achieved in differentiating between malignant and non-malignant DNA. In addition, DNA from the BCL and TCL groups exhibited differences in the area of the SERS band at 730 cm-1, yielding an AUC of 0.84 in differentiating between these two lymphadenopathies. Lastly, using multivariate data analysis techniques, an overall accuracy of 94.7% was achieved in the differential diagnosis between the BCL, TCL, Met and Ctr groups. These results pave the way towards the implementation of SERS as a novel tool in the clinical setting for improving the diagnosis of malignant lymphadenopathy.

Correlation between Volumes Determined by Echocardiography and Cardiac MRI in Controls and Atrial Fibrillation Patients.

AIMS: We aimed to compare cardiac volumes measured with echocardiography (echo) and cardiac magnetic resonance imaging (MRI) in a mixed cohort of healthy controls (controls) and patients with atrial fibrillation (AF). MATERIALS AND METHODS: In total, 123 subjects were included in our study; 99 full datasets were analyzed. All the participants underwent clinical evaluation, EKG, echo, and cardiac MRI acquisition. Participants with full clinical data were grouped into 63 AF patients and 36 controls for calculation of left atrial volume (LA Vol) and 51 AF patients and 30 controls for calculation of left ventricular end-diastolic volume (LV EDV), end-systolic volume (ESV), and LV ejection fraction (LV EF). RESULTS: No significant differences in LA Vol were observed (p > 0.05) when measured by either echo or MRI. However, echo provided significantly lower values for left ventricular volume (p < 0.0001). The echo LA Vol of all the subjects correlated well with that measured by MRI (Spearmen correlation coefficient r = 0.83, p < 0.0001). When comparing the two methods, significant positive correlations of EDV (all subjects: r = 0.55; Controls: r = 0.71; and AF patients: r = 0.51) and ESV (all subjects: r = 0.62; Controls: r = 0.47; and AF patients: r = 0.66) were found, with a negative bias for values determined using echo. For a subgroup of participants with ventricular volumes smaller than 49.50 mL, this bias was missing, thus in this case echocardiography could be used as an alternative for MRI. CONCLUSION: Good correlation and reduced bias were observed for LA Vol and EF determined by echo as compared to cardiac MRI in a mixed cohort of patients with AF and healthy volunteers. For the determination of volume values below 49.50 mL, an excellent correlation was observed between values obtained using echo and MRI, with comparatively reduced bias for the volumes determined by echo. Therefore, in certain cases, echocardiography could be used as a less expensive, less time-consuming, and contraindication free alternative to MRI for cardiac volume determination.

Students with Autism Spectrum Disorders and Their First-Year College Experiences.

Using data from the 2019 CIRP Freshman Survey and the Your First College Year (YFCY) from the Higher Education Research Institute at UCLA, this study explores the differences between the characteristics and behaviors of the first-year students with autism spectrum disorders (17) and those of students with learning disabilities (102). The findings indicate that the characteristics of these two groups of first-year college students were similar except for gender, ethnicity, first college generation, and parents' income. Compared with first-year college students with LD, students with ASD were less likely to engage in risk-taking behaviors, use health services and the writing center.

SERS liquid biopsy: An emerging tool for medical diagnosis.

Surface-enhanced Raman scattering (SERS) is emerging as a novel strategy for biofluid analysis. In this review, we delineate four experimental SERS protocols that are frequently used for the profiling of biofluids: 1) liquid SERS for the detection of purine metabolites; 2) iodide-modified liquid SERS for the detection of proteins; 3) dried SERS for the detection of both purine metabolites and proteins; 4) resonant Raman for the detection of carotenoids. To explain the selectivity of each experimental SERS protocol, we introduce a heuristic model for the chemisorption of analytes mediated by adsorbed ions (adions) onto the SERS substrate. Next, we show that the promising results of SERS liquid biopsy stem from the fact that the concentration levels of purine metabolites, proteins and carotenoids are informative of the cellular turnover rate, inflammation, and oxidative stress, respectively. These processes are perturbed in virtually every disease, from cancer to autoimmune maladies. Finally, we review recent SERS liquid biopsy studies and discuss future steps that are required for translating SERS in the clinical setting.

SERS-Based Evaluation of the DNA Methylation Pattern Associated With Progression in Clonal Leukemogenesis of Down Syndrome.

Here we show that surface-enhanced Raman scattering (SERS) analysis captures the relative hypomethylation of DNA from patients with acute leukemia associated with Down syndrome (AL-DS) compared with patients diagnosed with transient leukemia associated with Down syndrome (TL-DS), an information inferred from the area under the SERS band at 1005 cm-1 attributed to 5-methycytosine. The receiver operating characteristic (ROC) analysis of the area under the SERS band at 1005 cm-1 yielded an area under the curve (AUC) of 0.77 in differentiating between the AL-DS and TL-DS groups. In addition, we showed that DNA from patients with non-DS myeloproliferative neoplasm (non-DS-MPN) is hypomethylated compared to non-DS-AL, the area under the SERS band at 1005 cm-1 yielding an AUC of 0.78 in separating between non-DS-MPN and non-DS-AL. Overall, in this study, the area of the 1005 cm-1 DNA SERS marker band shows a stepwise decrease in DNA global methylation as cells progress from a pre-leukemia to a full-blown acute leukemia, highlighting thus the potential of SERS as an emerging method of analyzing the methylation landscape of DNA in the context of leukemia genesis and progression.

Adduct of Aquacobalamin with Hydrogen Peroxide.

Aquacobalamin binds hydrogen peroxide reversibly to form a cobalt(III) hydroperoxo adduct with a 0.25 mM dissociation constant, as evidenced by UV-vis absorption spectroscopy and corroborated by NMR, Raman spectroscopy, stopped-flow UV-vis measurements, and density functional theory calculations.

Assessment of Gold-Coated Iron Oxide Nanoparticles as Negative T2 Contrast Agent in Small Animal MRI Studies.

PURPOSE: Magnetic resonance imaging (MRI) contrast agents are pharmaceuticals that enable a better visualization of internal body structures. In this study, we present the synthesis, MRI signal enhancement capabilities, in vitro as well as in vivo cytotoxicity results of gold-coated iron oxide nanoparticles (Fe3O4@AuNPs) as potential contrast agents. METHODS: Fe3O4@AuNPs were obtained by synthesizing iron oxide nanoparticles and gradually coating them with gold. The obtained Fe3O4@AuNPs were characterized by spectroscopies, transmission electron microscopy (TEM) and energy dispersive X-ray diffraction. The effect of the nanoparticles on the MRI signal was tested using a 7T Bruker PharmaScan system. Cytotoxicity tests were made in vitro on Fe3O4@AuNP-treated retinal pigment epithelium cells by WST-1 tests and in vivo by following histopathological changes in rats after injection of Fe3O4@AuNPs. RESULTS: Stable Fe3O4@AuNPs were successfully prepared following a simple and fast protocol (<1h worktime) and identified using TEM. The cytotoxicity tests on cells have shown biocompatibility of Fe3O4@AuNPs at small concentrations of Fe (<1.95×10-8 mg/cell). Whereas, at higher Fe concentrations (eg 7.5×10-8 mg/cell), cell viability decreased to 80.88±5.03%, showing a mild cytotoxic effect. MRI tests on rats showed an optimal Fe3O4@AuNPs concentration of 6mg/100g body weight to obtain high-quality images. The histopathological studies revealed significant transient inflammatory responses in the time range from 2 hours to 14 days after injection and focal cellular alterations in several organs, with the lung being the most affected organ. These results were confirmed by hyperspectral microscopic imaging of the same, but unstained tissues. In most organs, the inflammatory responses and sublethal cellular damage appeared to be transitory, except for the kidneys, where the glomerular damage indicated progression towards glomerular sclerosis. CONCLUSION: The obtained stable, gold covered, iron oxide nanoparticles with reduced cytotoxicity, gave a negative T2 signal in the MRI, which makes them suitable for candidates as contrast agent in small animal MRI applications.

SERS-Based Assessment of MRD in Acute Promyelocytic Leukemia?

Acute promyelocytic leukemia (APL) is characterized by a unique chromosome translocation t(15;17)(q24;q21), which leads to the PML/RARA gene fusion formation. However, it is acknowledged that this rearrangement alone is not able to induce the whole leukemic phenotype. In addition, epigenetic processes, such as DNA methylation, may play a crucial role in leukemia pathogenesis. DNA methylation, catalyzed by DNA methyltransferases (DNMTs), involves the covalent transfer of a methyl group (-CH3) to the fifth carbon of the cytosine ring in the CpG dinucleotide and results in the formation of 5-methylcytosine (5-mC). The aberrant gene promoter methylation can be an alternative mechanism of tumor suppressor gene inactivation. Understanding cancer epigenetics and its pivotal role in oncogenesis, can offer us not only attractive targets for epigenetic treatment but can also provide powerful tools in monitoring the disease and estimating the prognosis. Several genes of interest, such as RARA, RARB, p15, p16, have been studied in APL and their methylation status was correlated with potential diagnostic and prognostic significance. In the present manuscript we comprehensively examine the current knowledge regarding DNA methylation in APL pathogenesis. We also discuss the perspectives of using the DNA methylation patterns as reliable biomarkers for measurable residual disease (MRD) monitoring and as a predictor of relapse. This work also highlights the possibility of detecting aberrant methylation profiles of circulating tumor DNA (ctDNA) through liquid biopsies, using the conventional methods, such as methylation-specific polymerase chain reaction (MS-PCR), sequencing methods, but also revolutionary methods, such as surface-enhanced Raman spectroscopy (SERS).

Combining surface-enhanced Raman scattering (SERS) of saliva and two-dimensional shear wave elastography (2D-SWE) of the parotid glands in the diagnosis of Sjögren's syndrome.

In this study, we combine the molecular structural information gained by SERS of saliva samples with the morphological data given by two-dimensional shear wave elastography (2D-SWE) (SuperSonic Imagine, Aixplorer) of parotid glands in the case of n = 31 patients with Sjögren's syndrome (SjS) and n = 22 controls, with the aim to discriminate between the two groups. The overall classification accuracy yielded by a hybrid principal component analysis-linear discriminant analysis (PCA-LDA) model based on both SERS and elastography (81%) was superior to that yielded by SERS spectra alone (75%) and elastography data alone (71%). This preliminary study is the first report on the use of 2D-SWE of parotid glands for the diagnosis of SjS as well as the first to describe the diagnosis of SjS based on the SERS spectra of dried saliva samples, the results suggesting that the strategy of combining the two methods could improve the diagnosis of SjS.

SERS-Based Liquid Biopsy of Gastrointestinal Tumors Using a Portable Raman Device Operating in a Clinical Environment.

Early diagnosis based on screening is recognized as one of the most efficient ways of mitigating cancer-associated morbidity and mortality. Therefore, reliable but cost-effective methodologies are needed. By using a portable Raman spectrometer, a small and easily transportable instrument, the needs of modern diagnosis in terms of rapidity, ease of use and flexibility are met. In this study, we analyzed the diagnostic accuracy yielded by the surface-enhanced Raman scattering (SERS)-based profiling of serum, performed with a portable Raman device operating in a real-life hospital environment, in the case of 53 patients with gastrointestinal tumors and 25 control subjects. The SERS spectra of serum displayed intense bands attributed to carotenoids and purine metabolites such as uric acid, xanthine and hypoxanthine, with different intensities between the cancer and control groups. Based on principal component analysis-quadratic discriminant analysis (PCA-QDA), the cancer and control groups were classified with an accuracy of 76.92%. By combining SERS spectra with general inflammatory markers such as C-reactive protein levels, neutrophil counts, platelet counts and hemoglobin levels, the discrimination accuracy was increased to 83.33%. This study highlights the potential of SERS-based liquid biopsy for the point-of-care diagnosis of gastrointestinal tumors using a portable Raman device operating in a clinical setting.

Math problem-solving and cognition among emerging bilingual children at risk and not at risk for math difficulties.

Cognitive processes that underlie individual differences in mathematical problem-solution accuracy in elementary emerging bilingual children (English Learners) at risk and not at risk for math problem-solving difficulties (MD) were examined. A battery of tests was administered in both English and Spanish that assessed problem-solving, achievement, and cognitive processing in children in first (N = 155/MD N = 23), second (N = 129/MD N = 44) and third grades (N = 110/MD N = 39). The results were that (a) the executive component of working memory (WM) predicted MD status independent of measures of fluid intelligence, reading, calculation, knowledge of algorithms, processing speed, short-term memory, and inhibition, (b) low performance on Spanish measures of numeracy and executive component of WM were major predictors of the odds of being classified as MD and (c) bilingual proficiency primarily moderated English rather than Spanish measures of cognition. The results support the notion that the executive system of WM is an important predictor of emerging bilingual children's math problem-solving difficulties.

The role of Ag+, Ca2+, Pb2+ and Al3+ adions in the SERS turn-on effect of anionic analytes.

In our recent studies we highlighted the role of adsorbed ions (adions) in turning on the surface-enhanced Raman scattering (SERS) effect in a specific mode for anionic and cationic analytes. In this work, we emphasize the role of Ag+, Ca2+, Pb2+ and Al3+ adions in the specific adsorption of anionic analytes such as the citrate capping agent and three organic acids. Our results suggest an adion-specific adsorption mechanism: the adsorption of anionic analytes is facilitated by positively charged adions such as Ag+, Ca2+, Pb2+ or Al3+, which provide adsorption sites specific for the anionic analytes. The turn-on of the SERS effect is explained in the context of the chemical mechanism of SERS. The adions form SERS-active sites on the silver surface enabling a charge transfer between the adsorbate and the silver surface. High-intensity SERS spectra of uric acid, salicylic acid and fumaric acid could be recorded at a concentration of 50 µM only after activation of the colloidal silver nanoparticles by Ca2+, Pb2+ or Al3+ (50 µM). The chemisorption of the three anionic species to the silver surface occurs competitively and is enhanced with the anions of higher affinities to the silver surface as indicated by the SERS spectra of corresponding mixed solutions.

Growth in Math Computation among Monolingual and English Language Learners:Does the Executive System have a Role?

This cohort-sequential study explored the components of working memory that underlie math calculation in elementary school children who are monolingual (English) or English language learners (ELLs) whose first language is Spanish. To this end, children (N = 789) in grades 1, 2, and 3 at wave 1 were administered a battery of math, vocabulary, reading and cognitive (short-term memory [STM], working memory [WM], rapid naming, and inhibition) measures. The battery of tests was administered again one year and two years later to the same participants. Three important findings emerged. First, along with naming speed, the results suggest that growth in the executive component of WM was significantly related to growth in calculation performance. Second, performance on measures of reading, fluid intelligence, naming speed and executive processes in wave 1 were significantly related to wave 3 math calculation performance. Finally, the full latent growth model showed that monolingual and ELL children were statistically comparable in computation at wave 3. Thus, strong support was found for the notion that the executive component of WM was related to math computation but weak support for the notion ELL children experienced a math achievement gap.

SERS assessment of the cancer-specific methylation pattern of genomic DNA: towards the detection of acute myeloid leukemia in patients undergoing hematopoietic stem cell transplantation.

In this label-free surface-enhanced Raman scattering (SERS) study of genomic DNA, we demonstrate that the cancer-specific DNA methylation pattern translates into specific spectral differences. Thus, DNA extracted from an acute myeloid leukemia (AML) cell line presented a decreased intensity of the 1005 cm-1 band of 5-methylcytosine compared to normal DNA, in line with the well-described hypomethylation of cancer DNA. The unique methylation pattern of cancer DNA also influences the DNA adsorption geometry, resulting in higher adenine SERS intensities for cancer DNA. The possibility of detecting cancer DNA based on its SERS spectrum was validated on peripheral blood genomic DNA samples from n = 17 AML patients and n = 17 control samples, yielding an overall classification of 82% based on the 1005 cm-1 band of 5-methylcytosine. By demonstrating the potential of SERS in assessing the methylation status in the case of real-life DNA samples, the study paves the way for novel methods of diagnosing cancer. Graphical abstract.

Individual differences in math problem solving and executive processing among emerging bilingual children.

This study identified cognitive processes that underlie individual differences in working memory (WM) and mathematical problem-solving accuracy in emerging bilingual children (English learners). A battery of tests was administered in both English and Spanish that assessed problem solving, achievement, and cognitive processing in children in first grade (n = 155), second grade (n = 129), and third grade (n = 110). The results were that (a) the executive component of WM predicted solution accuracy of word problems independent of first language and second language measures of vocabulary, reading, domain-specific knowledge (e.g., calculation, estimation), and short-term memory and (b) first language (Spanish) measures of the executive component of WM and magnitude comparisons were major predictors of math problem-solving accuracy in both languages. The results support the notion that the executive system of WM is a unique predictor of emerging bilingual children's math problem-solving accuracy in both languages.