Anoikis-related signature predicts prognosis and characterizes immune landscape of ovarian cancer.

Ovarian cancer (OV) is the most lethal gynecological malignancy worldwide, with high recurrence rates. Anoikis, a newly-acknowledged form of programmed cell death, plays an essential role in cancer progression, though studies focused on prognostic patterns of anoikis in OV are still lacking. We filtered 32 potential anoikis-related genes (ARGs) among the 6406 differentially expressed genes (DEGs) between the 180 normal controls and 376 TCGA-OV samples. Through the LASSO-Cox analysis, a 2-gene prognostic signature, namely AKT2, and DAPK1, was finally distinguished. We then demonstrated the promising prognostic value of the signature through the K-M survival analysis and time-dependent ROC curves (p-value < 0.05). Moreover, based on the signature and clinical features, we constructed and validated a nomogram model for 1-year, 3-year, and 5-year overall survival, with reliable prognostic values in both TCGA-OV training cohort (p-value < 0.001) and ICGC-OV validation cohort (p-value = 0.030). We evaluated the tumor immune landscape through the CIBERSORT algorithm, which indicated the upregulation of resting Myeloid Dendritic Cells (DCs), memory B cells, and naïve B cells and high expression of key immune checkpoint molecules (CD274 and PDCD1LG2) in the high-risk group. Interestingly, the high-risk group exhibited better sensitivity toward immunotherapy and less sensitivity toward chemotherapies, including Cisplatin and Bleomycin. Especially, based on the IHC of tissue microarrays among 125 OV patients at our institution, we reported that aberrant upregulation of DAPK1 was related to poor prognosis. Conclusively, the anoikis-related signature was a promising tool to evaluate prognosis and predict therapy responses, thus assisting decision-making in the realm of OV precision medicine.

Comprehensive machine learning-based preoperative blood features predict the prognosis for ovarian cancer.

PURPOSE: Significant advancements in improving ovarian cancer (OC) outcomes have been limited over the past decade. To predict prognosis and improve outcomes of OC, we plan to develop and validate a robust prognosis signature based on blood features. METHODS: We screened age and 33 blood features from 331 OC patients. Using ten machine learning algorithms, 88 combinations were generated, from which one was selected to construct a blood risk score (BRS) according to the highest C-index in the test dataset. RESULTS: Stepcox (both) and Enet (alpha = 0.7) performed the best in the test dataset with a C-index of 0.711. Meanwhile, the low RBS group possessed observably prolonged survival in this model. Compared to traditional prognostic-related features such as age, stage, grade, and CA125, our combined model had the highest AUC values at 3, 5, and 7 years. According to the results of the model, BRS can provide accurate predictions of OC prognosis. BRS was also capable of identifying various prognostic stratifications in different stages and grades. Importantly, developing the nomogram may improve performance by combining BRS and stage. CONCLUSION: This study provides a valuable combined machine-learning model that can be used for predicting the individualized prognosis of OC patients.

Cost-effectiveness analysis of hepatitis E vaccination strategies among patients with chronic hepatitis B in China.

AIM: This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in chronic hepatitis B (CHB) patients. METHODS: Based on the societal perspective, the cost-effectiveness of three hepatitis E vaccination strategies-vaccination without screening, screening-based vaccination, and no vaccination-among CHB patients was evaluated using a decision tree-Markov model, and incremental cost-effectiveness ratios (ICERs) were calculated. Values for treatment costs and health utilities were estimated from a prior investigation on disease burden, and values for transition probabilities and vaccination-related costs were obtained from previous studies and government agencies. Sensitivity analyses were undertaken for assessing model uncertainties. RESULTS: It was estimated that CHB patients superinfected with hepatitis E virus (HEV) incurred significantly longer disease course, higher economic burden, and more health loss compared to those with HEV infection alone (all p < 0.05). The ICERs of vaccination without screening and screening-based vaccination compared to no vaccination were 41,843.01 yuan/quality-adjusted life year (QALY) and 29,147.32 yuan/QALY, respectively, both lower than China's per-capita gross domestic product (GDP) in 2018. The screening-based vaccination reduced the cost and gained more QALYs than vaccination without screening. One-way sensitivity analyses revealed that vaccine price, vaccine protection rate, and decay rate of vaccine protection had the greatest impact on the cost-effectiveness analysis. Probabilistic sensitivity analyses confirmed the base-case results, and if the willingness-to-pay value reached per-capita GDP, the probability that screening-based vaccination would be cost-effective was approaching 100%. CONCLUSIONS: The disease burden in CHB patients superinfected with HEV is relatively heavy in China, and the screening-based hepatitis E vaccination strategy for CHB patients is the most cost-effective option.

Discovery of a potent and selective covalent threonine tyrosine kinase (TTK) inhibitor.

Threonine tyrosine kinase (TTK) is a critical component of the spindle assembly checkpoint and plays a pivotal role in mitosis. TTK has been identified as a potential therapeutic target for human cancers. Here, we describe our design, synthesis and evaluation of a class of covalent TTK inhibitors, exemplified by 16 (SYL1073). Compound 16 potently inhibits TTK kinase with an IC50 of 0.016 µM and displays improved selectivity in a panel of kinases. Mass spectrometry analysis reveals that 16 covalently binds to the C604 cysteine residue in the hinge region of the TTK kinase domain. Furthermore, 16 achieves strong potency in inhibiting the growth of various human cancer cell lines, outperforming its relative reversible inhibitor, and eliciting robust downstream effects. Taken together, compound 16 provides a valuable lead compound for further optimization toward the development of drug for treatment of human cancers.

Association Between CYP24A1 Polymorphisms and Bladder Cancer Risk in the Chinese Han Population.

In this cohort of 217 bladder cancer patients and 484 healthy controls, we explored the association between CYP24A1 variants (rs2762934, rs1570669, rs6068816, rs2296241) and bladder cancer risk in the Chinese Han population. Utilizing the Agena MassARRAY system, we genotyped four selected CYP24A1 polymorphisms. Logistic regression revealed a significant association of rs2762934 and rs1570669 with elevated bladder cancer risk, while rs6068816 exhibited a protective effect. Bioinformatics analysis of CYP24A1 expression in normal and cancerous bladder tissues indicated higher expression in normal tissue. In conclusion, our findings highlight the potential role of CYP24A1 variants in bladder cancer susceptibility.

Research on an SICM Scanning Image Resolution Enhancement Algorithm.

Scanning ion conductance microscopy (SICM) enables the non-invasive three-dimensional imaging of live cells and other structures in physiological environments. However, when imaging complex samples, SICM faces challenges such as having a low temporal resolution during slow scanning and a reduced signal-to-noise ratio during fast scanning, making it difficult to simultaneously improve both temporal and spatial resolution. To address these issues, this paper proposes an algorithm for enhancing image resolution under high-speed scanning. Firstly, scanning images are preprocessed using a median filtering algorithm to remove the salt-and-pepper noise generated during high-speed scanning. Next, the Canny edge detection algorithm is employed to extract the edges of the image targets. To avoid blurring the edges, the new edge-directed interpolation (NEDI) algorithm is then used to fill the edges, while non-edge areas are filled using bilinear interpolation, thereby enhancing the image resolution. Finally, the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM) are used to analyze the imaging of articular chondrocytes. The results show that under a scanning speed of 480 nm/ms, the proposed algorithm improves the temporal resolution of imaging by 60% compared to traditional 2× resolution imaging, increases the peak signal-to-noise ratio of the scanning images by 7 dB, and achieves a structural similarity of 0.97. Therefore, the proposed algorithm effectively removes noise during high-speed scanning and improves the SICM scanning imaging resolution, thereby avoiding the reduction in temporal resolution when scanning larger resolution samples and effectively enhancing the performance of SICM scanning imaging.

The neutrophil-lymphocyte ratio as a risk factor for all-cause and cardiovascular mortality among individuals with diabetes: evidence from the NHANES 2003-2016.

BACKGROUND: Evidence regarding the neutrophil-lymphocyte ratio (NLR) and mortality risk in diabetes patients is scarce. This study investigated the relationship of the NLR with all-cause and cardiovascular mortality risk in diabetes patients. METHODS: Diabetes patients (n = 3251) from seven National Health and Nutrition Examination Survey (NHANES) cycles (2003-2016) were included in this study. The cause of death and mortality status of the participants were obtained from National Death Index records. Restricted cubic spline (RCS) was used to visualize the association of the NLR with mortality risk. The maximally selected rank statistics method (MSRSM) was used to determine the optimal NLR cutoff value corresponding to the most significant association with survival outcomes. Weighted multivariable Cox regression models and subgroup analyses were adopted to assess the association of the NLR with all-cause and cardiovascular mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of the NLR in predicting survival outcomes. RESULTS: During a median follow-up of 91 months (interquartile range, 55-131 months), 896 (27.5%) of the 3251 diabetes patients died, including 261 (8.0%) with cardiovascular deaths and 635 (19.5%) with noncardiovascular deaths. The RCS regression analysis showed a positive linear association between the NLR and all-cause and cardiovascular mortality (both p > 0.05 for nonlinearity) in diabetes patients. Participants were divided into higher (> 3.48) and lower (≤ 3.48) NLR groups according to the MSRSM. In the multivariable-adjusted model, compared with participants with a lower NLR, those with a higher NLR had a significantly higher risk of both all-cause (HR 2.03, 95% confidence interval (CI) 1.64-2.51, p < 0.0001) and cardiovascular mortality (HR 2.76, 95% CI 1.84-4.14, p < 0.0001). The association was consistent in subgroup analyses based on age, sex, smoking status, drinking status, and hypertension, with no significant interaction between the aforementioned characteristics and the NLR (p interaction > 0.05). The time-dependent ROC curve showed that the areas under the curve of the 1-, 3-, 5-, and 10-year survival rates were 0.72, 0.66, 0.64, and 0.64 for all-cause mortality and 0.69, 0.71, 0.69 and 0.65, respectively, for cardiovascular mortality. CONCLUSION: An elevated NLR is independently associated with increased all-cause and cardiovascular mortality in diabetes patients.

Clinical significance and immune infiltration analyses of a novel coagulation-related signature in ovarian cancer.

Ovarian cancer (OV) is the most lethal gynecological malignancies worldwide. The coagulation cascade could induce tumor cell infiltration and contribute to OV progression. However, coagulation-related gene (CRG) signature for OV prognosis hasn't been determined yet. In this study, we evaluated the prognostic value of coagulation scores through receiver operating characteristics (ROC) analysis and K-M curves, among OV patients at our institution. Based on the transcriptome data of TCGA-OV cohort, we stratified two coagulation-related subtypes with distinct differences in prognosis and tumor immune microenvironment (p < 0.05). Moreover, from the 6406 differentially-expressed genes (DEGs) between the GTEx (n = 180) and TCGA-OV cohorts (n = 376), we identified 138 potential CRGs. Through LASSO-Cox algorithm, we finally distinguished a 3-gene signature (SERPINA10, CD38, and ZBTB16), with promising prognostic ability in both TCGA (p < 0.001) and ICGC cohorts (p = 0.040). Stepwise, we constructed a nomogram based on the clinical features and coagulation-related signature for overall survival prediction, with the C-index of 0.6761, which was evaluated by calibration curves. Especially, based on tissue microarrays analysis, Quantitative real-time fluorescence PCR (qRT-PCR), and Western Blot, we found that aberrant upregulation of CRGs was related to poor prognosis in OV at both mRNA and protein level (p < 0.05). Collectively, the coagulation-related signature was a robust prognostic biomarker, which could provide therapeutic benefits for chemotherapy/immunotherapy and assist clinical decision in OV patients.

Lower serum insulin-like growth factor-1 levels are independently associated with anemia in patients undergoing maintenance hemodialysis.

The relationship between serum insulin-like growth factor-1 (IGF-1) levels and anemia in patients undergoing maintenance hemodialysis (MHD) remains unclear. This cross-sectional study included patients who underwent MHD treatment for >3 months at our dialysis center in March 2021. Demographic and clinical data were recorded. Blood samples were collected before the hemodialysis sessions, and general serum biochemical parameters, routine blood markers, and serum IGF-1 levels were measured. Patients were divided into a group without anemia (hemoglobin ≥110 g/L) and a group with anemia (hemoglobin <110 g/L), and multivariable linear and binary logistic regression analyses were performed to study the relationship between the levels of serum IGF-1 and anemia. A total of 165 patients (male/female = 99:66) with MHD were enrolled in the study, with a median age of 66.0 (58.0, 75.0) years and a median dialysis vintage of 27.0 (12.0, 55.0) months. The mean hemoglobin level was 96.38 ± 16.72 g/L, and 126 patients had anemia (76.4%). Compared to patients without anemia, patients with anemia had lower serum IGF-1 and triglyceride levels and higher intravenous iron supplementation on dialysis (all p < 0.05). After adjusting for confounding factors in different models, the nine-model multivariate binary logistic regression analyses also confirmed that lower serum IGF-1 levels and serum IGF-1 < 197.03 ng/ml were both independently associated with anemia in patients undergoing MHD. However, further multicenter studies with larger sample sizes are required to confirm these findings.

Endoplasmic Reticulum Stress-Related Ten-Biomarker Risk Classifier for Survival Evaluation in Epithelial Ovarian Cancer and TRPM2: A Potential Therapeutic Target of Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignant tumor. Endoplasmic reticulum (ER) stress plays an important role in the malignant behaviors of several tumors. In this study, we established a risk classifier based on 10 differentially expressed genes related to ER stress to evaluate the prognosis of patients and help to develop novel medical decision-making for EOC cases. A total of 378 EOC cases with transcriptome data from the TCGA-OV public dataset were included. Cox regression analysis was used to establish a risk classifier based on 10 ER stress-related genes (ERGs). Then, through a variety of statistical methods, including survival analysis and receiver operating characteristic (ROC) methods, the prediction ability of the proposed classifier was tested and verified. Similar results were confirmed in the GEO cohort. In the immunoassay, the different subgroups showed different penetration levels of immune cells. Finally, we conducted loss-of-function experiments to silence TRPM2 in the human EOC cell line. We created a 10-ERG risk classifier that displays a powerful capability of survival evaluation for EOC cases, and TRPM2 could be a potential therapeutic target of ovarian cancer cells.

Nicotinamide reverses deficits in puberty-born neurons and cognitive function after maternal separation.

BACKGROUND: Early life stress (ELS) is associated with the development of schizophrenia later in life. The hippocampus develops significantly during childhood and is extremely reactive to stress. In rodent models, ELS can induce neuroinflammation, hippocampal neuronal loss, and schizophrenia-like behavior. While nicotinamide (NAM) can inhibit microglial inflammation, it is unknown whether NAM treatment during adolescence reduces hippocampal neuronal loss and abnormal behaviors induced by ELS. METHODS: Twenty-four hours of maternal separation (MS) of Wistar rat pups on post-natal day (PND)9 was used as an ELS. On PND35, animals received a single intraperitoneal injection of BrdU to label dividing neurons and were given NAM from PND35 to PND65. Behavioral testing was performed. Western blotting and immunofluorescence staining were used to detect nicotinamide adenine dinucleotide (NAD+)/Sirtuin3 (Sirt3)/superoxide dismutase 2 (SOD2) pathway-related proteins. RESULTS: Compared with controls, only MS animals in the adult stage (PND56-65) but not the adolescent stage (PND31-40) exhibited pre-pulse inhibition deficits and cognitive impairments mimicking schizophrenia symptoms. MS decreased the survival and activity of puberty-born neurons and hippocampal NAD+ and Sirt3 expression in adulthood. These observations were related to an increase in acetylated SOD2, microglial activation, and significant increases in pro-inflammatory IL-1ß, TNF-α, and IL-6 expression. All the effects of MS at PND9 were reversed by administering NAM in adolescence (PND35-65). CONCLUSIONS: MS may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. NAM may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior.

Nanomicelles co-loading CXCR4 antagonist and doxorubicin combat the refractory acute myeloid leukemia.

Acute myeloid leukemia (AML) is featured with poor prognosis and high mortality, because chemo-resistance, nonspecific distribution and dose-limiting toxicity lead to a high rate of relapse and a very low 5-year survival percentage of less than 25%. CXCR4 is a highly expressed chemokine receptor in multiple types of AML cells and closely associated with the drug resistance and relapse. In this work, we integrate a chemically synthesized CXCR4 antagonistic peptide and doxorubicin using DSPE-mPEG2000 micelles (referred to as M-E5-Dox) that is applied to a very challenging refractory AML mouse model as well as human AML cell lines. Results showed that M-E5-Dox can effectively bind to the CXCR4-expressing AML cells, downregulating the signaling proteins mediated by CXCR4/CXCL12 axis and increasing the cellular uptake of Dox. Importantly, M-E5-Dox remarkably decreases the leukemic cells in the peripheral blood and bone marrow, as well as their infiltration in the spleen and liver of the AML mice, which in turn prolongs the survival significantly. Meanwhile, M-E5-Dox did not increase the cardiotoxicity of Dox. In conclusion, M-E5-Dox harnesses the functions of CXCR4 specific binding and CXCR4 antagonism of the peptide and the tumor cell killing capacity of Dox, which displays significant therapeutic effects and promising translational potentials for the treatment of refractory AML.

Magnetic Nanofibrous Scaffolds Accelerate the Regeneration of Muscle Tissue in Combination with Extra Magnetic Fields.

The reversal of loss of the critical size of skeletal muscle is urgently required using biomaterial scaffolds to guide tissue regeneration. In this work, coaxial electrospun magnetic nanofibrous scaffolds were fabricated, with gelatin (Gel) as the shell of the fiber and polyurethane (PU) as the core. Iron oxide nanoparticles (Mag) of 10 nm diameter were added to the shell and core layer. Myoblast cells (C2C12) were cultured on the magnetic scaffolds and exposed to the applied magnetic fields. A mouse model of skeletal muscle injury was used to evaluate the repair guided by the scaffolds under the magnetic fields. It was shown that VEGF secretion and MyoG expression for the myoblast cells grown on the magnetic scaffolds under the magnetic fields were significantly increased, while, the gene expression of Myh4 was up-regulated. Results from an in vivo study indicated that the process of skeletal muscle regeneration in the mouse muscle injury model was accelerated by using the magnetic actuated strategy, which was verified by histochemical analysis, immunofluorescence staining of CD31, electrophysiological measurement and ultrasound imaging. In conclusion, the integration of a magnetic scaffold combined with the extra magnetic fields enhanced myoblast differentiation and VEGF secretion and accelerated the defect repair of skeletal muscle in situ.

Levels of trace blood elements associated with severe sleep disturbance in maintenance hemodialysis patients.

PURPOSE: Sleep disturbance is frequently observed in patients on maintenance hemodialysis (MHD), and this population usually presents imbalances in trace elements. We investigated the association between blood trace element levels and sleep quality in patients on MHD. METHODS: This cross-sectional and single-center study was performed in September 2019. Patients regularly undergoing hemodialysis for > 3 months at our center were recruited, and demographic, clinical, and laboratory parameters were recorded. The Pittsburgh Sleep Quality Index (PSQI) was applied to define sleep disturbance. Blood trace element (zinc, manganese, copper, selenium, and lead) levels were measured using an inductively coupled plasma mass spectrometer. RESULTS: In total, 121 patients on MHD (male/female = 68:53) were enrolled in the study (mean age 63.7 ± 13.9 years, median dialysis vintage 38.0 [20.0, 60.0] months). According to PSQI, 56 (46%) patients experienced severe sleep disturbance. These patients were characterized by older age, higher serum parathyroid hormone levels, and lower blood selenium levels (all P < 0.05). No significant differences in blood zinc, manganese, copper, and lead levels were observed between groups. Univariate binary logistic regression showed that lower blood selenium levels were associated with severe sleep disturbance (odds ratio = 0.976, 95% confidence interval: 0.954-0.999, P = 0.038). Multivariate analyses also confirmed the results after adjusting for confounding factors. CONCLUSION: Our study indicated an association between lower blood selenium levels and the occurrence of severe sleep disturbances in patients on MHD. However, a prospective study with a larger sample size and assessing the importance of selenium supplementation are needed to confirm the results.

Associations Between Blood Trace Element Levels and Nutritional Status in Maintenance Hemodialysis.

OBJECTIVE(S): We aimed to investigate the associations between blood trace element levels and nutritional status in patients undergoing maintenance hemodialysis (MHD). METHODS: This cross-sectional study included patients undergoing MHD who were treated at our center in September 2019. Clinical and demographic data and blood samples were collected before hemodialysis sessions, and the levels of manganese, lead, selenium, zinc, and copper were measured by inductively coupled plasma mass spectrometry. The Simplified Nutritional Appetite Questionnaire scale was used to assess patient appetite. Skinfold thickness, bicep circumference, upper arm muscle circumference, 7-point Subjective Global Assessment, Nutritional Risk Screening 2002 (NRS 2002), and Geriatric Nutritional Risk Index (GNRI) were used to assess patient nutritional status. Univariate and multivariate logistic regression analyses were performed to study the relationship between trace elements and nutritional indicators. RESULTS: In total, 118 patients (64 males and 54 females) were included, with a median dialysis vintage of 34.0 months (16.0-54.5 months) and an average age of 63.20 ± 14.26 years. Malnourished patients, as defined by the GNRI, Subjective Global Assessment, and NRS 2002, accounted for 28.0%, 49.2%, and 26.3% of enrolled patients, respectively. The multivariate binary logistic regression showed that higher blood copper levels were independently associated with nutritional risk defined as GNRI ≤91.2 (odds ratio [OR] = 1.003, 95% confidence interval [CI] = 1.000-1.006; P = .020), whereas lower blood zinc levels (OR = 0.634, 95% CI = 0.439-0.916; P = .015), blood zinc < 4.220 mg/L (OR = 3.723, 95% CI = 1.274-10.879; P = .016), lower blood selenium levels (OR = 0.959, 95% CI = 0.929-0.990; P = .010), and blood selenium < 85 µg/L (OR = 5.568, 95% CI = 1.039-29.840; P = .045) were independently associated with a nutritional risk defined as NRS 2002 ≥ 3. CONCLUSION(S): Higher levels of blood copper and lower levels of blood zinc and selenium were independently associated with higher nutritional risk in MHD patients.

Synthetic CXCR4 Antagonistic Peptide Assembling with Nanoscaled Micelles Combat Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the most common adult acute leukemia with very low survival rate due to drug resistance and high relapse rate. The C-X-C chemokine receptor 4 (CXCR4) is highly expressed by AML cells, actively mediating chemoresistance and reoccurrence. Herein, a chemically synthesized CXCR4 antagonistic peptide E5 is fabricated to micelle formulation (M-E5) and applied to refractory AML mice, and its therapeutic effects and pharmacokinetics are investigated. Results show that M-E5 can effectively block the surface CXCR4 in leukemic cells separated from bone marrow (BM) and spleen, and inhibit the C-X-C chemokine ligand 12-mediated migration. Subcutaneous administration of M-E5 significantly inhibits the engraftment of leukemic cells in spleen and BM, and mobilizes residue leukemic cells into peripheral blood, reducing organs' burden and significantly prolonging the survival of AML mice. M-E5 can also increase the efficacy of combining regime of homoharringtonine and doxorubicin. Ribonucleic acid sequencing demonstrates that the therapeutic effect is contributed by inhibiting proliferation and enhancing apoptosis and differentiation, all related to the CXCR4 signaling blockade. M-E5 reaches the concentration peak at 2 h after administration with a half-life of 14.5 h in blood. In conclusion, M-E5 is a novel promising therapeutic candidate for refractory AML treatment.

Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thyroid cancer (TC) is the most common endocrine system tumour. Several studies had revealed the potential of circulating microRNAs (miRNAs) as novel biomarkers for the diagnosis of TC. The purpose of this meta-analysis is to summarize published studies and evaluate the diagnostic accuracy of circulating miRNAs in TC detection. METHODS: In this meta-analysis, we systematically searched three databases: PubMed, EMBASE and Cochrane Library. We used the bivariate mixed-effects regression model to calculate the pooled diagnostic parameters and conduct the summary receiver operator characteristic curve (SROC). All calculations were performed using stata software. RESULTS: Thirty-five studies from 9 articles, including 663 TC patients, 519 patients with benign thyroid nodules (BTNs), and 84 healthy controls were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were 0.81 (95% CI 0.75-0.86), 0.81 (95% CI 0.75-0.86), 4.3 (95% CI 3.2-5.6), 0.24 (95% CI 0.18-0.31), 18 (95% CI 12-28) and 0.88 (95% CI 0.85-0.90), respectively in BTN controls, and 0.81 (95% CI 0.75-0.86), 0.85 (95% CI 0.75-0.91), 5.3 (95% CI 3.3-8.7), 0.23 (95% CI 0.18-0.29), 24 (95% CI 14-39), 0.89 (95% CI 0.86-0.91) in healthy controls. The subgroup analysis found that multiple miRNA assays had higher diagnostic accuracy than single miRNA assays with sensitivity of 0.88, specificity of 0.89 and AUC of 0.94. CONCLUSION: Circulating miRNAs have good values to diagnose TC and distinguish TC patients from BTN patients. MiRNAs can assist in the diagnosis of malignancy and avoid unnecessary surgery. In summary, circulating miRNAs should be added to our current clinical tools.

Computation Offloading in a Cognitive Vehicular Networks with Vehicular Cloud Computing and Remote Cloud Computing.

To satisfy the explosive growth of computation-intensive vehicular applications, we investigated the computation offloading problem in a cognitive vehicular networks (CVN). Specifically, in our scheme, the vehicular cloud computing (VCC)- and remote cloud computing (RCC)-enabled computation offloading were jointly considered. So far, extensive research has been conducted on RCC-based computation offloading, while the studies on VCC-based computation offloading are relatively rare. In fact, due to the dynamic and uncertainty of on-board resource, the VCC-based computation offloading is more challenging then the RCC one, especially under the vehicular scenario with expensive inter-vehicle communication or poor communication environment. To solve this problem, we propose to leverage the VCC's computation resource for computation offloading with a perception-exploitation way, which mainly comprise resource discovery and computation offloading two stages. In resource discovery stage, upon the action-observation history, a Long Short-Term Memory (LSTM) model is proposed to predict the on-board resource utilizing status at next time slot. Thereafter, based on the obtained computation resource distribution, a decentralized multi-agent Deep Reinforcement Learning (DRL) algorithm is proposed to solve the collaborative computation offloading with VCC and RCC. Last but not least, the proposed algorithms' effectiveness is verified with a host of numerical simulation results from different perspectives.

Comparable Outcomes of First-Line Hematopoietic Stem Cell Transplantation from Unrelated and Matched Sibling Donors in Adult Patients with Aplastic Anemia: A Retrospective Single-Center Study.

To explore the feasibility of upfront unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) in the treatment of adult aplastic anemia (AA), we conducted a retrospective, single-center study and compared the outcomes of adult patients who underwent first-line URD HSCT or matched sibling donor (MSD) HSCT between August 2012 and June 2018. In all, 23 URD HSCT recipients had an increased cumulative incidence of grade II acute graft-versus-host disease (aGVHD) (21.7% versus 3.4%; P =.007), but similar rates of secondary graft failure (8.7 ± 6.0% versus 6.9 ± 3.4%; P = .764), chronic GVHD (cGVHD) (18.2% versus 8.8%; P = .285), extensive cGVHD (9.1% versus 3.5%; P = .328), 5-year estimated overall survival (87.0% versus 94.2%; P = .501), and 5-year estimated failure-free survival (82.0% versus 89.3%; P = .404) compared with 58 MSD HSCT recipients treated during the same period. After using propensity score matching to reduce the influence of potential confounders, the 2 groups were well balanced in terms of pretransplantation clinical factors. The median survival time was similar, and no significant differences in the aforementioned outcomes were observed between the 2 groups. Our results suggest that URD HSCT may be an effective and feasible option for first-line therapy in adult AA patients who lack an MSD.

Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Severe Aplastic Anemia Patients with Infection: A Single-Center Retrospective Study.

To assess the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) patients with infection, we conducted a retrospective study on 65 SAA patients with infection who received allo-HSCT from August 2012 to December 2016. All patients received antibacterial and/or antifungal therapy before transplantation. The infection status after initial anti-infection therapy was classified as complete response (CR) (n = 14) or partial response/stable disease (PR/SD) (n = 51) before transplantation. The median times for myeloid engraftment in the PR/SD and CR groups were 10.5 days (range, 7 to 22) and 10 days (range, 8 to 11), with cumulative incidences of 98% and 100%, respectively. With a median follow-up of 788 days (range, 181 to 1758), patients with PR/SD had comparable results for 3-year estimated overall survival (85.4% versus 92.9%, P = .530) and 3-year failure-free survival (82.7% versus 92.9%, P = .458) with 14 patients with CR who received contemporaneous transplantation. In multivariate analysis, poor survival outcomes for the entire cohort was significantly associated with poor pretransplantation performance status. This retrospective study indicated that allo-HSCT may be a feasible therapeutic option for SAA patients with infection.