CircZBTB46 predicts poor prognosis and promotes disease progression of myelodysplastic syndromes and acute myeloid leukemia.

Circular RNAs (circRNAs) have been recently identified as important regulators of various diseases, especially cancer. However, the roles of circRNAs in hematologic malignancies have been rarely reported. This study aimed to identify a specific circRNA expression profile in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and to evaluate the biological roles of circRNA in MDS and AML for understanding their clinical significance. Reverse transcription-quantitative PCR was performed to validate the expression of circZBTB46. Kruskal-Wallis test, Kaplan-Meier curves, and the Cox regression model were employed to analyze the clinical significance of circZBTB46. Two specific shRNAs as well as an expression lentiviral vector of circZBTB46 were constructed to identify the biological function of circZBTB46. The impact of circZBTB46 on leukemia cell proliferation, cell cycle distribution, and apoptosis was confirmed using cell viability assay and flow cytometry analysis. The expression of circZBTB46 gradually increased in patients with higher-risk MDS and AML, as compared to controls. CircZBTB46 expression was significantly correlated with important clinical parameters of MDS, including WHO classification, absolute neutrophil count (ANC), marrow blast, IPSS karyotype, IPSS/IPSS-R risk groups, and AML transformation. CircZBTB46 expression was also associated with ANC, marrow blast, cytogenetic risk groups, FLT3-ITD mutation, and treatment response in AML patients. Furthermore, circZBTB46 overexpression was significantly correlated with shorter overall survival (OS, P = 0.0342, median survival time 18.5 vs. 45.4 months) and leukemia-free survival (LFS, P = 0.0421) in MDS, also with the shorter OS in AML (P = 0.0293, median survival time 11.6 vs. 16.9 months). Functional studies revealed that silencing circZBTB46 expression significantly inhibited proliferation and induced apoptosis in SKM-1, THP-1, and K562 cell lines, while rescue experiments alleviated the siRNA-mediated growth inhibition and apoptosis in these leukemic cells. The present data suggested the essential oncogenic role of circZBTB46, as a progression and survival indicator in both MDS and AML.

Plasma cell myeloma with RAS/BRAF mutations is frequently associated with a complex karyotype, advanced stage disease, and poorer prognosis.

BACKGROUND: Mutations in the RAS-MAPK pathway, such as KRAS, NRAS, and BRAF, are known as high-risk factors associated with poor prognosis in patients with various cancers, but studies in myeloma have yielded mixed results. METHODS: We describe the clinicopathologic, cytogenetic, molecular features, and outcomes of 68 patients with RAS/BRAF-mutated myeloma, and compare with 79 patients without any mutations. RESULTS: We show that KRAS, NRAS, and BRAF were mutated in 16%, 11%, and 5% of cases, respectively. RAS/BRAF-mutated patients had lower hemoglobin and platelet counts, higher levels of serum lactate dehydrogenase and calcium, higher percentage of bone marrow plasma cells, and more advanced R-ISS stage. RAS/BRAF mutations were associated with complex karyotype and gain/amplification of CKS1B. The median overall survival and progression-free survival were significantly shorter for RAS/BRAF-mutated patients (69.0 vs. 220.7 months, p = 0.0023 and 46.0 vs. 60.6 months, p = 0.0311, respectively). Univariate analysis revealed that KRAS mutation, NRAS mutation, lower hemoglobin, elevated lactate dehydrogenase, higher R-ISS stage, complex karyotype, gain/amplification of CKS1B, monosomy 13/RB1 deletion and lack of autologous stem cell transplantation were associated with poorer prognosis. Multivariate analysis showed that KRAS mutation, lower hemoglobin level, higher level of serum calcium, higher ISS stage, and lack of autologous stem cell transplantation predict inferior outcome. CONCLUSIONS: RAS/BRAF mutations occur in 30%-40% of myeloma cases and are associated with higher tumor burden, higher R-ISS stage, complex karyotype, and shorter overall survival and progression-free survival. These findings support testing for RAS/BRAF mutations in myeloma patients and underscore the potential therapeutic benefits of RAS/BRAF inhibitors.

Advances in molecular evaluation of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders with uncontrolled proliferation of one or more hematopoietic cell types, including myeloid, erythroid and megakaryocytic lineages, and minimal defect in maturation. Most MPN are associated with well-defined molecular abnormalities involving genes that encode protein tyrosine kinases that lead to constitutive activation of the downstream signal transduction pathways and confer cells proliferative and survival advantage. Genome-wide sequencing analyses have discovered secondary cooperating mutations that are shared by most of the MPN subtypes as well as other myeloid neoplasms and play a major role in disease progression. Without appropriate management, the natural history of most MPN consists of an initial chronic phase and a terminal blast phase. Molecular aberrations involving protein tyrosine kinases have been used for the diagnosis, classification, detection of minimal/measurable residual disease, and target therapy. We review recent advances in molecular genetic aberrations in MPN with a focus on MPN associated with gene rearrangements or mutations involving tyrosine kinase pathways.

ETNK1 mutation occurs in a wide spectrum of myeloid neoplasms and is not specific for atypical chronic myeloid leukemia.

BACKGROUND: ETNK1 mutation has been suggested as a useful tool to support the diagnosis of atypical chronic myeloid leukemia. ETNK1 mutations, however, occur in other myeloid neoplasms. METHODS: The authors assessed the clinicopathologic and molecular genetic features of 80 ETNK1-mutated myeloid neoplasms. RESULTS: Thirty-seven neoplasms (46%) were classified as myelodysplastic syndrome, 17 (21%) were classified as myelodysplastic/myeloproliferative neoplasm, 14 (18%) were classified as acute myeloid leukemia, and 12 (15%) were classified as myeloproliferative neoplasm. ETNK1 mutations were detected at the first test in 96% of patients, suggesting that ETNK1 mutation is an early event in pathogenesis. ETNK1 mutations represented the dominant clone in 63% of patients and was persistently dominant in 93%. The variant allele frequencies were usually higher in acute myeloid leukemia and increased upon leukemic transformation. ETNK1 mutation was accompanied by coexisting mutations in all patients, with ASXL1 (50%), TET2 (25%), EZH2 (24%), RUNX1 (24%), and SRSF2 (24%) mutations being the most common. Neoplasms with ETNK1 mutations were associated with morphologic dysplasia, increased blasts, myelofibrosis, and noncomplex karyotypes. With a median follow-up of 16.5 months, 30 patients died, 44 had persistent disease, and four achieved complete remission after stem cell transplantation. CONCLUSIONS: ETNK1 mutation is present in various myeloid neoplasms, often as an early event and a dominant clone and always with concurrent mutations. It may play an important role in the pathogenesis and progression of myeloid neoplasms by causing DNA damage and inducing other mutations and genomic instability, and it may serve as a potential therapeutic target. ETNK1 mutation is not disease-specific and should be interpreted with caution to classify myeloid neoplasms.

[Corrigendum] Role of 4­aminobutyrate aminotransferase (ABAT) and the lncRNA co­expression network in the development of myelodysplastic syndrome.

Subsequently to the publication of the above article, and a Corrigendum that has already been published with the intention of showing corrected versions of Figs. 1 and 8 (DOI: 10.3892/or.2022.8348; published online on June 14, 2022), the authors have belatedly realized that the revisions made to Fig. 8 necessitated changes that should have been introduced into Fig. 9, although these were not attended to in the first corrigendum. Essentially, Fig. 8 was revised as the cell apoptosis and cell proliferation assays therein were poorly presented, which made the interpretation of the data difficult; Fig. 9 showed the fractions of apoptotic cells in the SKM­1 and THP­1 cell lines with lncENST00000444102 overexpression as this pertained to Fig. 8. A revised version of Fig. 9, presenting the analysis of the data shown in the revised version of Fig. 8, is shown opposite. In addition to the revision of Fig. 9, the sentence starting on p. 517, left­hand column, line 12 ["The flow cytometric apoptosis assay revealed that lncENST00000444102 overexpression promoted tumor cells to undergo apoptosis compared to control cells (P<0.001, Fig. 9)"] should be replaced with the following text, to reflect the change in the level of statistical significance: 'The flow cytometric apoptosis assay revealed that lncENST00000444102 overexpression promoted tumor cells to undergo apoptosis compared to control cells (P<0.01, Fig. 9)". Note that the revisions made to Figs. 8 and 9 in this paper have not had a major impact on the reported results, and do not affect the overall conclusions reported in the study. All the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this additional Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [Oncology Reports 42: 509­520, 2019; DOI: 10.3892/or.2019.7175].

[Corrigendum] Role of 4­aminobutyrate aminotransferase (ABAT) and the lncRNA co­expression network in the development of myelodysplastic syndrome.

Following the publication of the above paper, the authors have realized that the cell apoptosis and cell proliferation assays in Fig. 8 were poorly presented, which made the interpretation of the data difficult. Furthermore, a change was also required to the text concerning the description of Fig. 8: The sentence starting on p. 517, left­hand column, line 7 ('The fraction of apoptotic cells was 22.41±2.596 in the lncENST00000444102-overexpressing SKM­1 cells, and 8.650±0.889 in the negative control; the fraction of apoptotic cells was 20.58±2.190 in the lncENST00000444102­overexpressing THP­1 cells and 8.192±0.997 in the negative control group (P<0.001, Fig. 8B)' should be replaced with the following text: 'Flow cytometry showed that the fraction of apoptotic cells increased in the lncENST00000444102­overexpressing SKM­1 and THP­1 cells, as determined by Annexin V­APC/7-AAD staining at 48 h (P<0.05; Fig. 8B)'. A revised version of Fig. 8, presenting the results of the flow cytometric analysis more clearly, is shown on the next page. Note that the revisions made to this figure have not had a major impact on the reported results, and do not affect the overall conclusions reported in the study. All the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [Oncology Reports 42: 509­520, 2019; DOI: 10.3892/or.2019.7175].

A Data Set and Deep Learning Algorithm for the Detection of Masses and Architectural Distortions in Digital Breast Tomosynthesis Images.

Importance: Breast cancer screening is among the most common radiological tasks, with more than 39 million examinations performed each year. While it has been among the most studied medical imaging applications of artificial intelligence, the development and evaluation of algorithms are hindered by the lack of well-annotated, large-scale publicly available data sets. Objectives: To curate, annotate, and make publicly available a large-scale data set of digital breast tomosynthesis (DBT) images to facilitate the development and evaluation of artificial intelligence algorithms for breast cancer screening; to develop a baseline deep learning model for breast cancer detection; and to test this model using the data set to serve as a baseline for future research. Design, Setting, and Participants: In this diagnostic study, 16 802 DBT examinations with at least 1 reconstruction view available, performed between August 26, 2014, and January 29, 2018, were obtained from Duke Health System and analyzed. From the initial cohort, examinations were divided into 4 groups and split into training and test sets for the development and evaluation of a deep learning model. Images with foreign objects or spot compression views were excluded. Data analysis was conducted from January 2018 to October 2020. Exposures: Screening DBT. Main Outcomes and Measures: The detection algorithm was evaluated with breast-based free-response receiver operating characteristic curve and sensitivity at 2 false positives per volume. Results: The curated data set contained 22 032 reconstructed DBT volumes that belonged to 5610 studies from 5060 patients with a mean (SD) age of 55 (11) years and 5059 (100.0%) women. This included 4 groups of studies: (1) 5129 (91.4%) normal studies; (2) 280 (5.0%) actionable studies, for which where additional imaging was needed but no biopsy was performed; (3) 112 (2.0%) benign biopsied studies; and (4) 89 studies (1.6%) with cancer. Our data set included masses and architectural distortions that were annotated by 2 experienced radiologists. Our deep learning model reached breast-based sensitivity of 65% (39 of 60; 95% CI, 56%-74%) at 2 false positives per DBT volume on a test set of 460 examinations from 418 patients. Conclusions and Relevance: The large, diverse, and curated data set presented in this study could facilitate the development and evaluation of artificial intelligence algorithms for breast cancer screening by providing data for training as well as a common set of cases for model validation. The performance of the model developed in this study showed that the task remains challenging; its performance could serve as a baseline for future model development.

Deep learning-based algorithm for assessment of knee osteoarthritis severity in radiographs matches performance of radiologists.

A fully-automated deep learning algorithm matched performance of radiologists in assessment of knee osteoarthritis severity in radiographs using the Kellgren-Lawrence grading system. PURPOSE: To develop an automated deep learning-based algorithm that jointly uses Posterior-Anterior (PA) and Lateral (LAT) views of knee radiographs to assess knee osteoarthritis severity according to the Kellgren-Lawrence grading system. MATERIALS AND METHODS: We used a dataset of 9739 exams from 2802 patients from Multicenter Osteoarthritis Study (MOST). The dataset was divided into a training set of 2040 patients, a validation set of 259 patients and a test set of 503 patients. A novel deep learning-based method was utilized for assessment of knee OA in two steps: (1) localization of knee joints in the images, (2) classification according to the KL grading system. Our method used both PA and LAT views as the input to the model. The scores generated by the algorithm were compared to the grades provided in the MOST dataset for the entire test set as well as grades provided by 5 radiologists at our institution for a subset of the test set. RESULTS: The model obtained a multi-class accuracy of 71.90% on the entire test set when compared to the ratings provided in the MOST dataset. The quadratic weighted Kappa coefficient for this set was 0.9066. The average quadratic weighted Kappa between all pairs of radiologists from our institution who took part in the study was 0.748. The average quadratic-weighted Kappa between the algorithm and the radiologists at our institution was 0.769. CONCLUSION: The proposed model performed demonstrated equivalency of KL classification to MSK radiologists, but clearly superior reproducibility. Our model also agreed with radiologists at our institution to the same extent as the radiologists with each other. The algorithm could be used to provide reproducible assessment of knee osteoarthritis severity.

Identification of circular RNAs as novel biomarkers and potentially functional competing endogenous RNA network for myelodysplastic syndrome patients.

Circular RNAs (circRNAs) have been identified to exert vital biological functions and can be used as new biomarkers in a number of tumors. However, little is known about the functions of circRNAs in myelodysplastic syndrome (MDS). Here, we aimed to investigate circRNA expression profiles and to investigate the functional and clinical value of circRNAs in MDS. Differential expression of circRNAs between MDS and control subjects was analyzed using circRNA arrays, in which we identified 145 upregulated circRNAs and 224 downregulated circRNAs. Validated by real-time quantitative PCR between 100 MDS patients and 20 controls, three upregulated (hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_104634) and three downregulated (hsa_circRNA_103846, hsa_circRNA_102817, and hsa_circRNA_102526) circRNAs matched the arrays. The receiver operating characteristic curve analysis of these circRNAs showed that the area under the curve was 0.7266, 0.8676, 0.7349, 0.7091, 0.8806, and 0.7472, respectively. Kaplan-Meier survival analysis showed that only hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817 were significantly associated with overall survival. Furthermore, we generated a competing endogenous RNA network focused on hsa_circRNA_100352, hsa_circRNA_104056, and hsa_circRNA_102817. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed that the three circRNAs were linked with some important cancer-related functions and pathways.

The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial.

Importance: It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA). Objective: To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA. Design, Setting, and Participants: This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018. Interventions: Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months. Main Outcomes and Measures: The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events. Results: Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events. Conclusions and Relevance: Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA. Trial Registration: ClinicalTrials.gov Identifier: NCT02631668.

LOC101928834, a novel lncRNA in Wnt/ß-catenin signaling pathway, promotes cell proliferation and predicts poor clinical outcome in myelodysplastic syndromes.

Long non-coding RNAs (lncRNAs) play important roles in hematological malignancies. We have previously identified several differentially expressed lncRNAs in myelodysplastic syndromes (MDS) by microarray analysis. In the present study, we explored the regulatory circuitry, potential functions, clinical and prognostic relevance of these lncRNAs in MDS by developing a lncRNA regulation network. We identified a novel lncRNA, LOC101928834, which was significantly up-regulated in the bone marrow of patients with MDS and acute myeloid leukemia (AML). We further evaluated the clinical relevance of LOC101928834 in 89 MDS and 110 AML patients and found that higher level of LOC101928834 expression was associated with higher white blood cell count, higher blast percentage, the subtype of refractory cytopenia with excess blasts (RAEB) and shorter overall survival in MDS patients. Receiver operating characteristic (ROC) curve analysis showed that LOC101928834 expression could discriminate MDS-RAEB patients from control with an area under the receiver-operating curve (AUC) of 0.9048. Moreover, functional analysis showed that LOC101928834 promoted cell proliferation and cell cycle progression, and activated Wnt/ß-catenin signaling pathway in vitro. In conclusion, LOC101928834 expression is correlated with clinical and biological features of MDS and may serve as a novel diagnostic and prognostic biomarker.

Role of 4­aminobutyrate aminotransferase (ABAT) and the lncRNA co­expression network in the development of myelodysplastic syndrome.

IncRNAs play an important role in the regulation of gene expression. The present study profiled differentially expressed lncRNAs (DELs) and mRNAs (DEMs) in myelodysplastic syndrome (MDS) to construct a 4­aminobutyrate aminotransferase (ABAT)­DEL­DEM co­expression network in MDS development using the Agilent human BeadChips and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network analyses. Compared with controls, there were 543 DELs and 2,705 DEMs in MDS patients, among which 285 (52.5%) DELs were downregulated and 258 (47.5%) DELs were upregulated, whereas 1,521 (56.2%) DEMs were downregulated and 1,184 (43.70%) DEMs were upregulated in MDS patients. The ABAT­DEL­DEM co­expression network contained six DELs that were co­expressed with ABAT in MDS. The GO analysis revealed that the co­expression network mainly participated in response to organic cyclic compound, cell proliferation, cell part morphogenesis, regulation of cell proliferation and enzyme­linked receptor protein signaling pathways, while the KEGG database showed that the co­expression network was involved in various pathways, such as phagosome and metabolic pathways. Furthermore, the expression of a selected DEL (lncENST00000444102) and ABAT was shown to be significantly downregulated in MDS patients, and in SKM­1 and THP­1 cells. The selected lncENST00000444102 was then overexpressed and ABAT expression was knocked down in the MDS cell lines using lentiviral transfection. In addition, lncENST00000444102 overexpression reduced the viability and increased the apoptosis of MDS cells, ABAT expression was upregulated by lncENST00000444102.

p53 and ß-Catenin Expression Predict Poorer Prognosis in Patients With Anaplastic Large-Cell Lymphoma.

BACKGROUND: The Wnt/ß-catenin signaling pathway is a major target of p53. ß-Catenin/p53 coexpression predicts poorer survival in carcinoma patients. Conversely, CD99 inhibits tumor metastasis through the Wnt/ß-catenin pathway. We therefore assessed p53, ß-catenin, and CD99 by immunohistochemistry. PATIENTS AND METHODS: We studied 45 patients with systemic anaplastic large-cell lymphoma (ALCL), including 20 anaplastic lymphoma kinase (ALK)-positive and 25 ALK-negative ALCL. ß-Catenin expression was analyzed using phospho-ß-catenin-S552 antibody because its nuclear localization indicates Wnt signaling. RESULTS: In this cohort, p53 expression was associated with ALK-negative ALCL. Furthermore, p53 or ß-catenin expression alone or ß-catenin/p53 double expression showed poorer overall survival and disease-free survival in patients with ALCL overall and in patients with ALK-negative ALCL. CD99 expression was more frequent in ALK-positive ALCL but had no prognostic significance. CONCLUSION: This is the first study to evaluate phospho-ß-catenin-S552 expression in ALCL. The results of this study, although limited by small patient size, suggest that ß-catenin and p53 may play a role in pathogenesis and may be helpful in risk stratification of ALCL patients.

An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms remain elusive. To provide insights on novel biomarkers for the diagnosis and therapy of MDS, we performed high-throughput genome-wide mRNA expression profiling, DNA methylation analysis, and long non-coding RNAs (lncRNA) analysis on bone marrows from four MDS patients and four age-matched healthy controls. We identified 1,937 differentially expressed genes (DEGs), 515 methylated genes, and 214 lncRNA that showed statistically significant differences. As the most significant module-related DEGs, TCL1A, PTGS2, and MME were revealed to be enriched in regulation of cell differentiation and cell death pathways. In addition, the GeneGo pathway maps identified by top DEGs were shown to converge on cancer, immunoregulation, apoptosis and regulation of actin cytoskeleton, most of which are known contributors in MDS etiology and pathogenesis. Notably, as potential biomarkers for diagnosis of MDS, four specific genes (ABAT, FADD, DAPP1, and SMPD3) were further subjected to detailed pathway analysis. Our integrative analysis on mRNA expression, gene methylation and lncRNAs profiling facilitates further understanding of the pathogenesis of MDS, and may promote the diagnosis and novel therapeutics for this disease.

Personalized Saliency and Its Prediction.

Nearly all existing visual saliency models by far have focused on predicting a universal saliency map across all observers. Yet psychology studies suggest that visual attention of different observers can vary significantly under specific circumstances, especially a scene is composed of multiple salient objects. To study such heterogenous visual attention pattern across observers, we first construct a personalized saliency dataset and explore correlations between visual attention, personal preferences, and image contents. Specifically, we propose to decompose a personalized saliency map (referred to as PSM) into a universal saliency map (referred to as USM) predictable by existing saliency detection models and a new discrepancy map across users that characterizes personalized saliency. We then present two solutions towards predicting such discrepancy maps, i.e., a multi-task convolutional neural network (CNN) framework and an extended CNN with Person-specific Information Encoded Filters (CNN-PIEF). Extensive experimental results demonstrate the effectiveness of our models for PSM prediction as well their generalization capability for unseen observers.

High methylation of the 4-aminobutyrate aminotransferase gene predicts a poor prognosis in patients with myelodysplastic syndrome.

In our previous study, the 4­aminobutyrate aminotransferase (ABAT) gene was screened and selected as a target gene that may affect the prognosis of myelodysplastic syndrome (MDS). The present study aimed to determine the prognostic value of ABAT in 152 patients with MDS, 29 patients with acute myeloid leukemia (AML) and 40 controls, by detecting the expression and methylation levels of the ABAT gene. In patients with MDS, the expression levels of ABAT were significantly reduced compared with in the controls (P<0.0001), and the degree of DNA methylation was increased in MDS subjects (P<0.0001). Age, hemoglobin level, marrow blasts, International Prognostic Scoring System karyotype, and the expression and methylation levels of ABAT were associated with overall survival (OS), as determined by univariate analysis. Multivariate analysis revealed that older age, higher marrow blasts and higher methylation percentage were independent risk factors for OS. In addition, a functional study demonstrated that ABAT gene silencing increased cell apoptosis and blocked the G1/S phase in SKM­1 and THP­1 human leukemia cells. A γ­aminobutyrate aminotransferase inhibitor also blocked the G1/S phase; however, it had no effect on cell apoptosis. In conclusion, the present study demonstrated that ABAT methylation served an essential role in the progression of MDS and therefore may be considered an indicator of poor prognosis for hematological malignancies.

Synergistic inhibitory effects of deferasirox in combination with decitabine on leukemia cell lines SKM-1, THP-1, and K-562.

A multi-center study from the French Myelodysplastic Syndrome (MDS) Group confirmed that iron chelation therapy is an independent prognostic factor that can increase the survival rate of patients who are suffering from transfusion-dependent low-risk MDS. In this study, we aimed to explore this clinical phenomena in vitro, by exploring the synergistic effect of the iron chelator Deferasirox (DFX) and the DNA methyl transferase inhibitor Decitabine (DAC) in the leukemia cell lines SKM-1, THP-1, and K-562. Treatment with both DFX or DAC promoted apoptosis, induced cell cycle arrest, and inhibited proliferation in all three of these cell lines. The combination of DFX and DAC was much greater than the effect of using either drug alone. DFX showed a synergistic effect with DAC on cell apoptosis in all three cell lines and on cell cycle arrest at the G0/G1 phase in K-562 cells. DFX decreased the ROS levels to varying degrees. In contrast, DAC increased ROS levels and an increase in ROS was also noted when the two drugs were used in combination. Treatment of cells with DAC induced re-expression of ABAT, APAF-1, FADD, HJV, and SMPD3, presumably through demethylation. However the combination of DAC and DFX just had strong synergistic effect on the re-expression of HJV.

Saliency Detection on Light Field.

Existing saliency detection approaches use images as inputs and are sensitive to foreground/background similarities, complex background textures, and occlusions. We explore the problem of using light fields as input for saliency detection. Our technique is enabled by the availability of commercial plenoptic cameras that capture the light field of a scene in a single shot. We show that the unique refocusing capability of light fields provides useful focusness, depths, and objectness cues. We further develop a new saliency detection algorithm tailored for light fields. To validate our approach, we acquire a light field database of a range of indoor and outdoor scenes and generate the ground truth saliency map. Experiments show that our saliency detection scheme can robustly handle challenging scenarios such as similar foreground and background, cluttered background, complex occlusions, etc., and achieve high accuracy and robustness.

[Whole genome methylation profiles of myelodysplastic syndrome and its diagnostic value].

OBJECTIVE: To identify methylation profiles in myelodysplastic syndrome (MDS) and to provide the biomarkers for the early diagnosis and differential diagnosis of MDS. METHODS: Genes were screened for hypermethylation by genome-wide DNA methylation profiles. Transcription down-regulation was determined with a gene expression microarray. Methylation-specific, real-time, and bisulfite-sequencing PCR cloning and sequencing were performed to validate selected genes in MDS cases and non-malignant hematologic diseases (controls). Diagnostic test, such as sensitivity and specificity, was used to evaluate the value of methylation patterns. RESULTS: A draft of methylation patterns was established and refined to 6 genes after validation in 211 patients and 60 controls. The hypermethylated genes were ABAT (97%), DAPP1 (98%), FADD (89%), LRRFIP1 (96%), PLBD1 (89%), and SMPD3 (85%). A combination of 5 or more than 5 genes showed a specificity of 95% and sensitivity of 91.4% for the diagnosis of MDS. The accuracy of diagnosis was 92.3%. CONCLUSION: We demonstrated here that the ABAT, DAPP1, FADD, LRRFIP1, PLBD1 and SMPD3 genes are hypermethylated and downregulated in MDS. The six genes could be the markers of the methylation patterns in MDS, as a noninvasive approach for the diagnosis of MDS.