A novel RNA in situ hybridization assay for the long noncoding RNA SChLAP1 predicts poor clinical outcome after radical prostatectomy in clinically localized prostate cancer.

Long noncoding RNAs (lncRNAs) are an emerging class of oncogenic molecules implicated in a diverse range of human malignancies. We recently identified SChLAP1 as a novel lncRNA that demonstrates outlier expression in a subset of prostate cancers, promotes tumor cell invasion and metastasis, and associates with lethal disease. Based on these findings, we sought to develop an RNA in situ hybridization (ISH) assay for SChLAP1 to 1) investigate the spectrum of SChLAP1 expression from benign prostatic tissue to metastatic castration-resistant prostate cancer and 2) to determine whether SChLAP1 expression by ISH is associated with outcome after radical prostatectomy in patients with clinically localized disease. The results from our current study demonstrate that SChLAP1 expression increases with prostate cancer progression, and high SChLAP1 expression by ISH is associated with poor outcome after radical prostatectomy in patients with clinically localized prostate cancer by both univariate (hazard ratio = 2.343, P = .005) and multivariate (hazard ratio = 1.99, P = .032) Cox regression analyses. This study highlights a potential clinical utility for SChLAP1 ISH as a novel tissue-based biomarker assay for outcome prognostication after radical prostatectomy

Serum electrolyte levels in relation to macrovascular complications in Chinese patients with diabetes mellitus

BACKGROUND: The prevalence of diabetes in China is increasing rapidly. However, scarce data are available on serum electrolyte levels in Chinese adults with diabetes, especially in those with cardiovascular complications. This study measured serum electrolyte levels and examined their relationship with macrovascular complications in Chinese adults with diabetes. METHODS: The three gender- and age-matched groups were enrolled into this analysis, which were 1,170 subjects with normal glucose regulation (NGR), 389 with impaired glucose regulation (IGR) and 343 with diabetes. Fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2hPG), glycosylated hemoglobin A1c (HbA1c) and serum electrolyte levels were measured. Data collection included ankle brachial index results. RESULTS: Serum sodium and magnesium levels in the diabetes group were significantly decreased compared to the NGR group (sodium: 141.0 ± 2.4 vs. 142.1 ± 2.0 mmol/l; magnesium: 0.88 ± 0.08 vs. 0.91 ± 0.07 mmol/l, all P < 0.01), while the serum calcium level was significantly increased (2.36 ± 0.11 vs. 2.33 ± 0.09 mmol/l, P < 0.01). Multiple linear regression showed that serum sodium and magnesium levels in the diabetes group were negatively correlated with FPG, 2hPG and HbA1c (sodium: Std β = −0.35, -0.19, -0.25; magnesium: Std β = −0.29, -0.17, -0.34, all P < 0.01), while the serum calcium level was positively correlated with HbA1c (Std β = 0.17, P < 0.05). In diabetic subjects, serum sodium, magnesium and potassium levels were decreased in the subjects with the elevation of estimated glomerular filtration rates (P < 0.05). ANCOVA analysis suggested that serum magnesium level in subjects with diabetic macrovascular complications was significantly decreased compared with diabetic subjects without macrovascular complications after the effect of some possible confounding being removed (P < 0.05). CONCLUSIONS: Serum sodium and magnesium levels were decreased in Chinese subjects with diabetes, while the observed increase in calcium level correlated with increasing glucose level. Diabetic patients with macrovascular complications had lower serum magnesium level than those with no macrovascular complications

IR Design for Application-Specific Natural Language: A Case Study on Traffic Data

In the realm of software applications in the transportation industry, Domain-Specific Languages (DSLs) have enjoyed widespread adoption due to their ease of use and various other benefits. With the ceaseless progress in computer performance and the rapid development of large-scale models, the possibility of programming using natural language in specified applications - referred to as Application-Specific Natural Language (ASNL) - has emerged. ASNL exhibits greater flexibility and freedom, which, in turn, leads to an increase in computational complexity for parsing and a decrease in processing performance. To tackle this issue, our paper advances a design for an intermediate representation (IR) that caters to ASNL and can uniformly process transportation data into graph data format, improving data processing performance. Experimental comparisons reveal that in standard data query operations, our proposed IR design can achieve a speed improvement of over forty times compared to direct usage of standard XML format data

Development of energy plants from hybrids between Miscanthus sacchariflorus and M. lutarioriparius grown on reclaimed mine land in the Loess Plateau of China

Miscanthus, a promising bioenergy plant, has a high biomass yield with high cellulose content suitable for biofuel production. However, harsh climatic and poor soil conditions, such as barren lands or abandoned mines, pose a challenge to the survival and yield of Miscanthus feedstock on the marginal land. The selection from the interspecific hybrids of Miscanthus might combine high survival rates and high yield, which benefits energy crop development in multi-stressful environments. A total of 113 F1 hybrids between Miscanthus sacchariflorus and M. lutarioriparius together with the parents were planted and evaluated for multiple morphological and physiological traits on the mine land of the Loess Plateau of China. The majority of hybrids had higher establishment rates than M. sacchariflorus while M. lutarioriparius failed to survive for the first winter. Nearly all hybrid genotypes outperformed M. lutarioriparius for yield-related traits including plant height, tiller number, tiller diameter, and leaf area. The average biomass of the hybrids was 20 times higher than that of surviving parent, M. sacchariflorus. Furthermore, the photosynthetic rates and water use efficiency of the hybrids were both significantly higher than those of the parents, which might be partly responsible for their higher yield. A total of 29 hybrids with outstanding traits related to yield and stress tolerance were identified as candidates. The study investigated for the first time the hybrids between local individuals of M. sacchariflorus and high-biomass M. lutarioriparius, suggesting that this could be an effective approach for high-yield energy crop development on vast of marginal lands

Clinical prognostic factors for central neurocytoma and subgroup analysis of different treatment measures: A SEER database-based retrospective analysis from 2003 to 2019

PurposeThe study aimed to identify clinical prognostic factors affecting overall survival (OS) in patients with central neurocytoma (CN) and to determine independent prognostic factors in the subgroups of different treatment modalities using a retrospective analysis based on the SEER database from 2003 to 2019.Materials and methodsData regarding patients with CN, including basic clinical characteristics, treatment measures, and prognosis follow-up, were extracted from the SEER database. The prognostic variables for all patients were assessed using log-rank test as well as univariate and multivariate analyses based on the Cox proportional hazards model. The same statistical methods were used for analysis in different subgroups of gross total resection (GTR), subtotal resection (STR), no surgery, radiotherapy (RT), and no RT.ResultsIn total, 413 patients were enrolled in this study. Tumor size, primary site surgery, and RT were independent prognostic factors in all patients with CN. In subgroup analyses, RT was not an independent prognostic factor in patients with GTR. However, sex and race were independent prognostic factors in patients with STR. Additionally, tumor size was an independent prognostic factor in patients who did not undergo surgery. Furthermore, sex and primary site were independent prognostic factors in patients who received RT. Size and primary site surgery were independent prognostic factors in patients without RT.ConclusionIn our study, patients with small tumors or GTR or those who did not receive RT showed a better prognosis. GTR was the preferred treatment for CN. RT was not recommended for patients after GTR. Men and African American showed certain advantages after STR surgery. Tumors with a size of &gt;4 cm were recommended for active treatment. In the RT subgroup, patients with tumors outside the ventricle or women had a poorer prognosis than those with tumors within the ventricle or men, respectively. These findings will help clinicians and patients understand the treatment and prognosis of CN visually and intuitively

Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression

Multiple, complex molecular events characterize cancer development and progression(1,2). Deciphering the molecular networks that distinguish organ- confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high- throughput liquid- and- gas- chromatography- based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer ( 42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N- methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non- invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine- N- methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.Early Detection Research Network ; National Institutes of Health ; MTTC ; Clinical Translational Science Award ; Fund for Discovery of the University of Michigan Comprehensive Cancer Center ; University of Michigan Cancer Biostatistics Training Grant ; Doris Duke Charitable FoundationWe thank J. Granger for help in manuscript preparation, J. Siddiqui and R. Varambally for help with the clinical database, and A. Vellaichamy and S. Pullela for technical assistance. We thank K. Pienta for access to metastatic prostate cancer samples from the University of Michigan Prostate SPORE rapid autopsy programme. This work is supported in part by the Early Detection Research Network (A.M.C., J.T.W.), National Institutes of Health (A.S., S.P., J.B., T.M.R., D.G., G.S.O. and A.M.C.) and an MTTC grant (G.S.O. and A.S.). A.M.C. is supported by a Clinical Translational Science Award from the Burroughs Welcome Foundation. A. S. is supported by a grant from the Fund for Discovery of the University of Michigan Comprehensive Cancer Center. L. M. P. is supported by the University of Michigan Cancer Biostatistics Training Grant. A. M. C and S. P. are supported by the Doris Duke Charitable Foundation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62661/1/nature07762.pd

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets