CanCellVar: A database for single-cell variants map in human cancer.

Numerous variants, including both single-nucleotide variants (SNVs) in DNA and A>G RNA edits in mRNA as essential drivers of cellular proliferation and tumorigenesis, are commonly associated with cancer progression and growth. Thus, mining and summarizing single-cell variants will provide a refined and higher-resolution view of cancer and further contribute to precision medicine. Here, we established a database, CanCellVar, which aims to provide and visualize the comprehensive atlas of single-cell variants in tumor microenvironment. The current CanCellVar identified ∼3 million variants (∼1.4 million SNVs and ∼1.4 million A>G RNA edits) involved in 2,754,531 cells of 5 major cell types across 37 cancer types. CanCellVar provides the basic annotation information as well as cellular and molecular function properties of variants. In addition, the clinical relevance of variants can be obtained including tumor grade, treatment, metastasis, and others. Several flexible tools were also developed to aid retrieval and to analyze cell-cell interactions, gene expression, cell-development trajectories, regulation, and molecular structure affected by variants. Collectively, CanCellVar will serve as a valuable resource for investigating the functions and characteristics of single-cell variations and their roles in human tumor evolution and treatment.

PRES: a webserver for decoding the functional perturbations of RNA editing sites.

Rapid progresses in RNA-Seq and computational methods have assisted in quantifying A-to-I RNA editing and altered RNA editing sites have been widely observed in various diseases. Nevertheless, functional characterization of the altered RNA editing sites still remains a challenge. Here, we developed perturbations of RNA editing sites (PRES; http://bio-bigdata.hrbmu.edu.cn/PRES/) as the webserver for decoding functional perturbations of RNA editing sites based on editome profiling. After uploading an editome profile among samples of different groups, PRES will first annotate the editing sites to various genomic elements and detect differential editing sites under the user-selected method and thresholds. Next, the downstream functional perturbations of differential editing sites will be characterized from gain or loss miRNA/RNA binding protein regulation, RNA and protein structure changes, and the perturbed biological pathways. A prioritization module was developed to rank genes based on their functional consequences of RNA editing events. PRES provides user-friendly functionalities, ultra-efficient calculation, intuitive table and figure visualization interface to display the annotated RNA editing events, filtering options and elaborate application notebooks. We anticipate PRES will provide an opportunity for better understanding the regulatory mechanisms of RNA editing in human complex diseases.

Electrochemical Sensors Based on Self-Assembling Peptide/Carbon Nanotube Nanocomposites for Sensitive Detection of Bisphenol A.

In this study, a cationic amphiphilic self-assembling peptide (SAP) Z23 was designed, and a simple bisphenol a (BPA) sensor, based on SAP Z23/multiwalled carbon nanotubes (Z23/MWCNTs) composite, was successfully fabricated on the surface of a glassy carbon electrode (GCE). The composite material was formed by π-π stacking interaction between the aromatic group on the hydrophobic side of Z23 and the side-wall of MWCNTs, with the charged hydrophilic group of Z23 exposed. During the electrocatalytic process of BPA, a synergistic effect was observed between Z23 and MWCNTs. The current response of the sensor based on composite material was 3.24 times that of the MWCNTs-modified electrode, which was much higher than that of the peptide-based electrode. Differential pulse voltammetry (DPV) was used to optimize the experimental conditions affecting the analytical performance of the modified electrode. Under optimal conditions, the linear range of the sensor was from 10 nM to 100 µM by amperometric measurement with sensitivity and limit of detection (LOD) at 6.569 µAµM-1cm-2 and 1.28 nM (S/N = 3), respectively. Consequently, the sensor has excellent electrochemical performance and is easy to fabricate, making it a good prospect in the field of electrochemical detection in the future.

Impact of Nd Doping on Electronic, Optical, and Magnetic Properties of ZnO: A GGA + U Study.

The electronic, optical, and magnetic properties of Nd-doped ZnO systems were calculated using the DFT/GGA + U method. According to the results, the Nd dopant causes lattice parameter expansion, negative formation energy, and bandgap narrowing, resulting in the formation of an N-type degenerate semiconductor. Overlapping of the generated impurity and Fermi levels results in a significant trap effect that prevents electron-hole recombination. The absorption spectrum demonstrates a redshift in the visible region, and the intensity increased, leading to enhanced photocatalytic performance. The Nd-doped ZnO system displays ferromagnetic, with FM coupling due to strong spd-f hybridization through magnetic exchange interaction between the Nd-4f state and O-2p, Zn-4s, and Zn-3p states. These findings imply that Nd-doped ZnO may be a promising material for DMS spintronic devices.

Dysregulation in Multiple Transcriptomic Endometrial Pathways Is Associated with Recurrent Implantation Failure and Recurrent Early Pregnancy Loss.

Overlapping disease aetiologies associated with multiple altered biological processes have been identified that change the endometrial function leading to recurrent implantation failure (RIF) and recurrent early pregnancy loss (REPL). We aimed to provide a detailed insight into the nature of the biological malfunction and related pathways of differentially expressed genes in RIF and REPL. Endometrial biopsies were obtained from 9 women experiencing RIF, REPL and control groups. Affymetrix microarray analysis was performed to measure the gene expression level of the endometrial biopsies. Unsupervised clustering of endometrial samples shows scattered distribution of gene expression between the RIF, REPL and control groups. 2556 and 1174 genes (p value < 0.05, Fold change > 1.2) were significantly altered in the endometria of RIF and REPL patients' group, respectively compared to the control group. Downregulation in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the differentially expressed genes (DEGs) in RIF and REPL including ribosome and oxidative phosphorylation pathways. Gene Ontology (GO) analysis revealed ribosomes and mitochondria inner membrane as the most significantly downregulated cellular component (CC) affected in RIF and REPL. Determination of the dysregulated genes and related biological pathways in RIF and REPL will be key in understanding their molecular pathology and of major importance in addressing diagnosis, prognosis, and treatment issues

Association Studies of ERCC2 rs13181 Polymorphism with Pancreatic Cancer Susceptibility.

Although the ERCC2 gene rs13181 polymorphism is involved in the pancreatic cancer pathogenic mechanism, there is no consistent finding. This meta-analysis aimed to determine the association between ERCC2 rs13181 polymorphism and pancreatic cancer. Related articles were searched against the PubMed database in a retrospective way. Additionally, the combined odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated using the random- or fixed-effects model. Altogether, seven articles regarding ERCC2 gene rs13181 polymorphism were enrolled. The combined ORs regarding the relationship of ERCC2 rs13181 polymorphism with pancreatic cancer incidence showed significant differences in each genetic model (C vs. A: OR = 1.14, 95% CI = 1.04-1.26; CC vs. AA: OR = 1.53, 95% CI = 1.24-1.90; AC vs. AA: OR = 1.06, 95% CI 0.92-1.22; recessive model: OR = 1.50, 95% CI = 1.22-1.84; dominant model: OR = 1.16, 95% CI = 1.02-1.32). Additionally, we performed subgroup analysis stratified by race, which revealed that ERCC2 rs13181 polymorphism increased the risk of pancreatic cancer in Asian populations. This work suggests that the ERCC2 gene rs13181 polymorphism is related to pancreatic cancer risk in Asians.

Survey of miRNA-miRNA cooperative regulation principles across cancer types.

Cooperative regulation among multiple microRNAs (miRNAs) is a complex type of posttranscriptional regulation in human; however, the global view of the system-level regulatory principles across cancers is still unclear. Here, we investigated miRNA-miRNA cooperative regulatory landscape across 18 cancer types and summarized the regulatory principles of miRNAs. The miRNA-miRNA cooperative pan-cancer network exhibited a scale-free and modular architecture. Cancer types with similar tissue origins had high similarity in cooperative network structure and expression of cooperative miRNA pairs. In addition, cooperative miRNAs showed divergent properties, including higher expression, greater expression variation and a stronger regulatory strength towards targets and were likely to regulate cancer hallmark-related functions. We found a marked rewiring of miRNA-miRNA cooperation between various cancers and revealed conserved and rewired network miRNA hubs. We further identified the common hubs, cancer-specific hubs and other hubs, which tend to target known anticancer drug targets. Finally, miRNA cooperative modules were found to be associated with patient survival in several cancer types. Our study highlights the potential of pan-cancer miRNA-miRNA cooperative regulation as a novel paradigm that may aid in the discovery of tumorigenesis mechanisms and development of anticancer drugs.

Periprocedural risk factors for incomplete radiofrequency ablation of liver metastases from colorectal cancer: a single-center retrospective analysis.

OBJECTIVE: To explore independent risk factors for incomplete radiofrequency ablation (iRFA) of colorectal cancer liver metastases (CRLM) and evaluate adverse outcomes following iRFA. MATERIALS AND METHODS: Magnetic resonance imaging data of CRLM patients who received percutaneous RFA were randomized into training (70%) and validation set 1 (30%) data sets. An independent validation set 2 was derived from computed tomography scans. Uni- and multivariate analyses identified independent risk factors for iRFA. Area under the curve (AUC) values were used to evaluate the predictive model performance. Risk points were assigned to independent predictors, and iRFA was predicted according to the total risk score. Kaplan-Meier curves were used to assess new intrahepatic metastases (NIHM), unablated tumor progression, and overall survival (OS). RESULTS: Multivariate regression determined as independent iRFA risk factors perivascular tumor location, subcapsular tumor location, tumor size ≥20 mm, and minimal ablative margin ≤5 mm. The AUC values of the model in the training set, validation set 1, and validation set 2 were 0.867, 0.772, and 0.820, respectively. The respective AUC values of the total risk score were 0.864, 0.768, and 0.817. During the 6-year follow-up, the cumulative OS was significantly shorter in the iRFA than in the complete RFA group, and NIHM (hazard ratio [HR] = 2.79; 95% confidence interval [CI]: 1.725, 4.513) and unablated tumor progression (HR = 3.473; 95% CI: 1.506, 8.007) were more severe. CONCLUSIONS: Perivascular tumor location, subcapsular tumor location, tumor size ≥20 mm, and minimal ablative margin ≤5 mm were independent risk factors for iRFA. iRFA may be a potential predictor of NIHM, unablated tumor progression, and OS.

RBP EIF2S2 Promotes Tumorigenesis and Progression by Regulating MYC-Mediated Inhibition via FHIT-Related Enhancers.

RNA-binding proteins (RBPs) play fundamental roles in cancer; however, we still lack knowledge about to what extent RBPs are dysregulated, as well as about perturbed signaling pathways in cancer. In this study, we integrated analysis of multidimensional data across >10,000 cancer patients and >1,000 cell lines. We identified a top candidate RBP: eukaryotic translation initiation factor 2 subunit beta (EIF2S2). EIF2S2 is highly expressed in tumors and is associated with malignant features as well as patient prognosis. Functional assays performed in cancer cells revealed that EIF2S2 promotes cancer cell proliferation, migration, and invasion in vitro as well as tumor growth and metastasis in vivo. Mechanistic investigations further demonstrated that EIF2S2 promotes tumorigenesis and progression by directly binding to a long non-coding RNA, LINC01600, which physically interacts with the MYC protein and increases its stability. Interestingly, we revealed that the EIF2S2-LINC01600-MYC axis can activate the Wnt/ß-catenin pathway by inhibiting the activity of FHIT-related enhancers and FHIT expression. Finally, EIF2S2 knockdown combined with oxaliplatin treatment could be a potential combination therapy in cancer. Our integrated analysis provided detailed knowledge of the function of the EIF2S2-LINC01600-MYC axis, which will facilitate the development of rational combination therapies for cancer.

MIR22HG acts as a tumor suppressor via TGFß/SMAD signaling and facilitates immunotherapy in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as critical regulatory elements and play fundamental roles in the biology of various cancers. However, we are still lack of knowledge about their expression patterns and functions in human colorectal cancer (CRC). METHODS: Differentially expressed lncRNAs in CRC were identified by bioinformatics screen and the level of MIR22HG in CRC and control tissues were determined by qRT-PCR. Cell viability and migration capacities were examined by MTT and transwell assay. Mouse model was used to examine the function and rational immunotherapy of MIR22HG in vivo. RESULTS: We systematically investigated the expression pattern of lncRNAs and revealed MIR22HG acts as a tumor suppressor in CRC. The expression of MIR22HG was significantly decreased in CRC, which was mainly driven by copy number deletion. Reduced expression of MIR22HG was significantly associated with poor overall survival. Silencing of MIR22HG promoted cell survival, proliferation and tumor metastasis in vitro and in vivo. Mechanistically, MIR22HG exerts its tumor suppressive activity by competitively interacting with SMAD2 and modulating the activity of TGFß pathway. Decreased MIR22HG promoted the epithelial-mesenchymal transition in CRC. Importantly, we found that MIR22HG expression is significantly correlated with CD8A and overexpression of MIR22HG triggers T cell infiltration, enhancing the clinical benefits of immunotherapy. CONCLUSION: MIR22HG acts as a tumor suppressor in CRC. Our data provide mechanistic insights into the regulation of MIR22HG in TGFß pathway and facilitates immunotherapy in cancer.

Targeted delivery of mitomycin C-loaded and LDL-conjugated mesoporous silica nanoparticles for inhibiting the proliferation of pterygium subconjunctival fibroblasts.

Pterygium is a degenerative disease that characterized by excessive fibrovascular proliferation. To reduce the recurrence rate, surgery is the main strategy, in combination with adjacent procedures or adjunctive therapy. One of the most common adjunctive agents, mitomycin C (MMC), is known as an alkylating agent that inhibits fibroblast proliferation but is limitedly applied in pterygium due to various complications. A previous study demonstrated that activated pterygium subconjunctival fibroblasts overexpressed low-density lipoprotein (LDL) receptors. In this study, we designed and synthesized MMC-loaded mesoporous silica nanoparticles conjugated with LDL (MMC@MSNs-LDL) to deliver MMC into activated pterygium fibroblasts in a targeted manner. The MMC loading efficiency was approximately 6%. The cell viability test (CCK-8 assay) revealed no cytotoxicity for the empty carrier MSNs at a concentration of ≤1 mg/ml after administration for 48 h in subconjunctival fibroblasts. Primary pterygium and normal human subconjunctival fibroblasts with or without stimulation by vascular endothelial growth factor (VEGF) were treated as follows: 1) 10 µg/ml MMC@MSNs-LDL for 24 h (MMC concentration: 0.6 µg/ml); 2) 0.2 mg/ml MMC for 5 min then cultured for 24 h after MMC removal; and 3) normal culture without any drug treatment. At 24 h, the anti-proliferative effect of MMC@MSNs-LDL in activated pterygium fibroblasts was similar to that of MMC (cell viability: 46.2 ± 5.5% vs 40.5 ± 1.1%, respectively, P = 0.349). Furthermore, the cytotoxicity of MMC@MSNs-LDL to normal fibroblasts with or without VEGF stimulation was significantly lower than that of traditional MMC (cell viability: 75.6 ± 4.4% vs 36.0 ± 1.5%, respectively, P < 0.001; 84.7 ± 5.5% vs 35.7 ± 1.3%, P < 0.001). The binding of fluorescently labeled MMC@MSNs-LDL in fibroblasts was assessed using confocal fluorescence microscopy. The uptake of targeted nanoparticles in fibroblasts was time dependent and saturated at 6 h. VEGF-activated pterygium fibroblasts showed more uptake of MMC@MSNs-LDL than normal fibroblasts with or without VEGF activation (both P < 0.001). Our data strongly suggest that MMC@MSNs-LDL had an effective antiproliferative role in activated pterygium fibroblasts, with reduced toxicity to normal fibroblasts compared to traditional application of MMC. LDL-mediated drug delivery might have great potential in the management of pterygium recurrence.

miRNA-miRNA crosstalk: from genomics to phenomics.

The discovery of microRNA (miRNA)-miRNA crosstalk has greatly improved our understanding of complex gene regulatory networks in normal and disease-specific physiological conditions. Numerous approaches have been proposed for modeling miRNA-miRNA networks based on genomic sequences, miRNA-mRNA regulation, functional information and phenomics alone, or by integrating heterogeneous data. In addition, it is expected that miRNA-miRNA crosstalk can be reprogrammed in different tissues or specific diseases. Thus, transcriptome data have also been integrated to construct context-specific miRNA-miRNA networks. In this review, we summarize the state-of-the-art miRNA-miRNA network modeling methods, which range from genomics to phenomics, where we focus on the need to integrate heterogeneous types of omics data. Finally, we suggest future directions for studies of crosstalk of noncoding RNAs. This comprehensive summarization and discussion elucidated in this work provide constructive insights into miRNA-miRNA crosstalk.

High expression of miR-363 predicts poor prognosis and guides treatment selection in acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous malignancy with various outcomes, and therefore needs better risk stratification tools to help select optimal therapeutic options. METHODS: In this study, we identify miRNAs that could predict clinical outcome in a heterogeneous AML population using TCGA dataset. RESULTS: We found that MiR-363 is a novel prognostic factor in AML patients undergoing chemotherapy. In multivariable analyses, high miR-363 remained predictive for shorter OS (HR = 2.349, P = 0.012) and EFS (HR = 2.082, P = 0.001) independent of other well-known prognostic factors. More importantly, allogeneic hematopoietic stem cell transplantation (allo-HSCT) overcame the adverse outcomes related to high miR-363 expression. In gene expression profiling, high miR-363 expression was positively correlated with the amounts of leukemogenic transcription factors, including Myb, RUNX3, GATA3, IKZF3, ETS1 and MLLT3. Notably, we found that the in silico predicted target genes (EZH2, KLF6 and PTEN) of miR-363 were downregulated in association with high miR-363 expression. CONCLUSIONS: In summary, miR-363 expression may help identify patients in need of strategies to select the optimal therapy between chemotherapeutic and allo-HCST regimens. AML patients with high miR-363 expression may be highly recommended for early allo-HSCT regimen.

High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) pertains to a hematologic malignancy with heterogeneous therapeutic responses. Improvements in risk stratification in AML patients are warranted. MicroRNAs have been associated with the pathogenesis of AML. METHODS: To examine the prognostic value of miR-25, 162 cases with de novo AML were classified into two groups according to different treatment regimens. RESULTS: In the chemotherapy group, cases with upregulated miR-25 expression showed relatively longer overall survival (OS; P = 0.0086) and event-free survival (EFS; P = 0.019). Multivariable analyses revealed that miR-25 upregulation is an independent predictor for extended OS (HR = 0.556, P = 0.015) and EFS (HR = 0.598, P = 0.03). In addition, allogeneic hematopoietic stem cell transplantation (allo-HSCT) circumvented the poor prognosis that was related to miR-25 downregulation with chemotherapy. The expression level pattern of miR-25 coincided with AML differentiation and proliferation, which included HOXA and HOXB cluster members, as well as the HOX cofactor MEIS1. The MYH9 gene was identified as a direct target of miR-25. CONCLUSIONS: The miR-25 levels are correlated with prognosis in AML independently of other powerful molecular markers. The expression of miR-25 may contribute to the selection of the optimal treatment regimen between chemotherapy and allo-HCST for AML patients.

Evaluation of corneal cross-linking as adjuvant therapy for the management of fungal keratitis.

PURPOSE: To evaluate the efficacy of corneal cross-linking (CXL) as adjuvant therapy for the treatment of fungal ulcerative keratitis. METHODS: Forty-one patients with fungal ulcerative keratitis were recruited and assigned into two randomized controlled groups. These groups were treated with CXL combined with antifungal medications (CXL-M) or antifungal medications alone (M). The ulcers were assessed by slit-lamp biomicroscopy, slit-lamp images, in vivo confocal microscopy (IVCM), and anterior segment optical coherence tomography (AS-OCT). The patients were followed up before surgery/first visit (FV), 1 day after surgery, 1 and 2 weeks, and 1, 2, 3, 4, 5, and 6 months after surgery/FV. RESULTS: In the cured patients, the area of corneal ulcers, the duration of ulcer healing, the time to non-observed fungal hyphae by IVCM, the number of antifungal medications, the frequency of administered medications, and the maximum ulcer depth decreased significantly after CXL (all P < 0.05) compared with the M group. There were no significant differences in either corneal thickness or epithelial thickness of ulcers after healing between 5 and 6 months after surgery in the CXL-M group, while these were increased significantly at 6 months compared with 5 months after FV in the M group (both P < 0.05). CONCLUSIONS: In our study, CXL accelerated healing of the fungal ulcers, shortened the treatment duration, and minimized the need for medications and surgery. It appears that CXL is an effective procedure and adjuvant therapy for managing fungal keratitis.

Evaluation of the ocular surface characteristics and Demodex infestation in paediatric and adult blepharokeratoconjunctivitis.

BACKGROUND: To evaluate the ocular surface characteristics and the infestation of Demodex in Chinese paediatric and adult blepharokeratoconjunctivitis (BKC). METHODS: Fifty consecutive patients with BKC and 50 age- and sex-matched healthy subjects were enrolled. Lid margin characteristics and corneal disorders were evaluated under slit-lamp illumination. Four eyelashes were collected from each eye to examine Demodex infestation by light microscopy. RESULTS: Corneal neovascularization (P = 0.001) and scarring (P = 0.040) were significantly worse in children than in adults with BKC, whereas meibum quality was worse in adults (P = 0.008). Diagnosis delay was longer in children with BKC than in adults (2.2 vs 1.2 years, P = 0.022). Demodex infestation was more frequent in subjects with BKC than in healthy subjects (56% vs 26%, P = 0.002). The lid margin inflammation and meibomian gland dysfunction were worse in Demodex-positive subjects than in Demodex-negative subjects with BKC. CONCLUSIONS: Children with BKC had severer corneal disorders compared with adult BKC patients, which may be caused by a long-delayed diagnosis. Ocular demodicosis was more common in subjects with BKC. Ocular Demodex infestation was associated with worse lid margin inflammation and meibomian gland dysfunction.

CircRNA circHIPK3 serves as a prognostic marker to promote glioma progression by regulating miR-654/IGF2BP3 signaling.

Emerging evidences show RNA back-splicing produces a new type of noncoding RNA, namely circular RNA (circRNA). Many reports demonstrate that circRNA circHIPK3 exerts oncogenic or anti-tumor roles in different cancers, such as ovarian cancer, bladder cancer, osteosarcoma, colorectal cancer and liver cancer. However, no study about circHIPK3 function in glioma exists until today. In this study, we showed that circHIPK3 was upregulated in glioma tissues. Elevated level of circHIPK3 was linked to poor prognosis. Functional investigation indicated that circHIPK3 promotes glioma cell proliferation and invasion, and tumor propagation in vivo. Furthermore, miR-654 was identified as a target of circHIPK3 while IGF2BP3 was targeted by miR-654. CircHIPK3 could promote IGF2BP3 expression via interacting with miR-654 in glioma cells. Finally, CCK8 and transwell assays illustrated that IGF2BP3 overexpression could reverse the effects of IGF2BP3 depletion. Altogether, our findings demonstrated that circHIPK3 contributes to glioma progression through targeting miR-654 from IGF2BP3 and implies circHIPK3 might be a potential target for glioma therapy.

MiR-425 expression profiling in acute myeloid leukemia might guide the treatment choice between allogeneic transplantation and chemotherapy.

BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous disease. MicroRNAs function as important biomarkers in the clinical prognosis of AML. METHODS: This study identified miR-425 as a prognostic factor in AML by screening the TCGA dataset. A total of 162 patients with AML were enrolled for the study and divided into chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) groups. RESULTS: In the chemotherapy group, patients with high miR-425 expression had significantly longer overall survival (OS) and event-free survival (EFS) compared with patients with low miR-425 expression. In multivariate analyses, high miR-425 expression remained independently predictive of a better OS (HR = 0.502, P = 0.005) and EFS (HR = 0.432, P = 0.001) compared with patients with low miR-425 expression. Then, all patients were divided into two groups based on the median expression levels of miR-425. Notably, the patients undergoing allo-HSCT had significantly better OS (HR = 0.302, P < 0.0001) and EFS (HR = 0.379, P < 0.0001) compared with patients treated with chemotherapy in the low-miR-425-expression group. Mechanistically, high miR-425 expression levels were associated with a profile significantly involved in regulating cellular metabolism. Among these genes, MAP3K5, SMAD2, and SMAD5 were predicted targets of miR-425. CONCLUSIONS: The expression of miR-425 may be useful in identifying patients in need of strategies to select the optimal therapy between chemotherapy and allo-HSCT treatment regimens. Patients with low miR-425 expression may consider early allo-HSCT.

Metabolite-cycled STEAM and semi-LASER localization for MR spectroscopy of the human brain at 9.4T.

PURPOSE: Metabolite cycling (MC) is an MRS technique for the simultaneous acquisition of water and metabolite spectra that avoids chemical exchange saturation transfer effects and for which water may serve as a reference signal or contain additional information in functional or diffusion studies. Here, MC was developed for human investigations at ultrahigh field. METHODS: MC-STEAM and MC-semi-LASER are introduced at 9.4T with an optimized inversion pulse and elaborate coil setup. Experimental and simulation results are given for the implementation of adiabatic inversion pulses for MC. The two techniques are compared, and the effect of frequency and phase correction based on the MC water spectra is evaluated. Finally, absolute quantification of metabolites is performed. RESULTS: The proposed coil configuration results in a maximum B1 + of 48 µΤ in a voxel within the occipital lobe. Frequency and phase correction of single acquisitions improve signal-to-noise ratio (SNR) and linewidth, leading to high-resolution spectra. The improvement of SNR of N-acetylaspartate (SNRNAA ) for frequency aligned data, acquired with MC-STEAM and MC-semi-LASER, are 37% and 30%, respectively (P < 0.05). Moreover, a doubling of the SNRNAA for MC-semi-LASER in comparison with MC-STEAM is observed (P < 0.05). Concentration levels for 18 metabolites from the human occipital lobe are reported, as acquired with both MC-STEAM and MC-semi-LASER. CONCLUSION: This work introduces a novel methodology for single-voxel MRS on a 9.4T whole-body scanner and highlights the advantages of semi-LASER compared to STEAM in terms of excitation profile. In comparison with MC-STEAM, MC-semi-LASER yields spectra with higher SNR. Magn Reson Med 79:1841-1850, 2018. © 2017 International Society for Magnetic Resonance in Medicine.