mRNA-CLA: An interpretable deep learning approach for predicting mRNA subcellular localization.

Messenger RNA (mRNA) is vital for post-transcriptional gene regulation, acting as the direct template for protein synthesis. However, the methods available for predicting mRNA subcellular localization need to be improved and enhanced. Notably, few existing algorithms can annotate mRNA sequences with multiple localizations. In this work, we propose the mRNA-CLA, an innovative multi-label subcellular localization prediction framework for mRNA, leveraging a deep learning approach with a multi-head self-attention mechanism. The framework employs a multi-scale convolutional layer to extract sequence features across different regions and uses a self-attention mechanism explicitly designed for each sequence. Paired with Position Weight Matrices (PWMs) derived from the convolutional neural network layers, our model offers interpretability in the analysis. In particular, we perform a base-level analysis of mRNA sequences from diverse subcellular localizations to determine the nucleotide specificity corresponding to each site. Our evaluations demonstrate that the mRNA-CLA model substantially outperforms existing methods and tools.

Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

Introduction: Early diagnosis of Parkinson's disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR-positive exosomes, no studies have examined ferritin and TfR in plasma neural-derived exosomes. Methods: Plasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models. Results: Neural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/µg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/µg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000-1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression. Conclusion: It is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD.

Yin-Yang tongue sign: An imaging clue of lesions involving the skull base segment in the hypoglossal pathway.

OBJECTIVE: To investigate the diagnostic value of the Yin-Yang tongue sign in patients with tongue deviation. METHODS: According to the presence of the Yin-Yang tongue sign on CT/MR, 107 patients with tongue deviation were divided into a positive group and a negative group. The involvement categories of the hypoglossal canal (HC) in the positive group were evaluated and classified as HC dilation and HC erosion. The correlations between HC involvement categories and the presence of the sign were analysed. RESULTS: There were 55 cases (55/107, 51.4%) in the positive group and 52 cases (52/107, 48.6%) in the negative group. Hypoglossal nerve (HN) involvement mainly occurred in the skull base (61.8%), skull base and carotid space (10.9%), and carotid space segment (12.7%). Neurogenic (50.9%), squamous cell carcinoma (14.5%), and metastases (12.7%) were the predominant aetiologies. The sensitivity, specificity, and accuracy of this sign for suggesting skull base lesions around HC were 72.4%, 80.8%, and 76.6%, respectively. In the positive group, HC dilation was seen in 21 patients (21/55, 38.2%) and 21 cases were all benign. HC erosion were noted in 19 patients (19/55, 34.5%), of whom 12 cases were malignant. CONCLUSION: The Yin-Yang tongue sign is formed by unilateral tongue atrophy and fat infiltration caused by lesions in the HN pathway, especially compressive or invasive lesions involving the skull base segment.

Corrigendum: Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

[This corrects the article DOI: 10.3389/fnagi.2023.1216905.].

First detection and phylogenetic analysis of lumpy skin disease virus from Kinmen Island, Taiwan in 2020.

Lumpy skin disease is an arthropod-borne bovine disease caused by lumpy skin disease virus. A suspect lumpy skin disease case in a breeding cattle farm on Kinmen Island, Taiwan was reported on July 8, 2020 and later confirmed the first occurrence of lumpy skin disease in the country by molecular biological detections, electron microscopy, and sequence comparison. Implementation of control measures including blanket vaccination on the island effectively ceased the outbreaks. Phylogenetic analyses revealed that the virus discovered in the outbreaks was most similar to those identified in China in 2019. Identifying this virus in the coastal areas in East Asia indicated the rapid eastward spread of lumpy skin disease in Asia.

Functional magnetic resonance imaging evaluation of masticatory muscle dysfunction in unilateral exodontia rabbits.

OBJECTIVE: Occlusal alteration due to tooth loss may cause overload of masticatory muscle and promote muscle dysfunction. This study explored the feasibility of using functional magnetic resonance imaging (fMRI) to evaluate muscle dysfunction in an established unilateral exodontia animal model. METHODS: 6 rabbits were extracted right maxillary molars. T2 mapping, T2* mapping and Iterative Decomposition of water and fat with Echo Asymmetry and Least Square Estimation (IDEAL-IQ) were performed one day before extraction and every 2 weeks (2th~12th week) after extraction. The T2 and T2* values and fat fraction (FF) of bilateral temporal muscle (TM), masseter muscle (MM) and medial pterygoid muscle (MPM) were measured and compared between the extraction side and the contralateral side. Parameters of three monitoring time points (0th, 6th, 12th week) were also analyzed. RESULTS: T2 values of MM on extraction side were significantly higher than those of contralateral side-from fourth week to 12th week after extraction (p < 0.05). T2 values of MM and MPM on extraction side and TM on contralateral side were significantly higher in 12th week than those in 0th week (p < 0.05). And FF of bilateral MM was significantly higher in 12th week than those in 0th week (p < 0.05). T2* value showed no significant difference between extraction side and contralateral side and also at above three time points. CONCLUSION: T2 and T2* value and FF can be used as indicators of masticatory muscle dysfunction. fMRI is expected to be a non-invasive method for in vivo and real-time evaluation of masticatory muscle functional abnormality.

Diffusion Tensor Imaging of the Lateral Pterygoid Muscle in Patients with Temporomandibular Joint Disorders and Healthy Volunteers.

OBJECTIVE: This study aimed to explore the feasibility of functional evaluation of the lateral pterygoid muscle (LPM) using diffusion tensor imaging (DTI) in patients with temporomandibular joint disorders (TMDs). MATERIALS AND METHODS: A total of 119 patients with TMD (23 male and 96 female; mean age ± standard deviation, 41 ± 15 years; 58 bilateral and 61 unilateral involvements for a total of 177 joints) and 20 healthy volunteers (9 male and 11 female; 40 ± 13 years; 40 joints) were included in this prospective study. Based on DTI of the jaw in the resting state, the diffusion parameters, apparent diffusion coefficient (ADC), fractional anisotropy (FA), λ1, λ2, and λ3 of the superior and inferior heads of the LPM (SHLPM and IHLPM) were measured. Patients with TMD with normal disc position (ND), anterior disc displacement with reduction (ADWR), and anterior disc displacement without reduction (ADWOR) were compared. RESULTS: Patients with TMD overall, and ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 in both the SHLPM and IHLPM than those in volunteers (p < 0.05 for all), whereas the ND subgroup only had significantly higher ADC and λ1 (p < 0.001). Meanwhile, significant differences in FA in the SHLPM and IHLPM were found between volunteers and ADWOR (p = 0.014 and p = 0.037, respectively). Among the three TMD subgroups, except for λ3 and FA in the ADWR subgroup, ADWR and ADWOR subgroups had significantly higher ADC, λ1, λ2, and λ3 and lower FA than those in the ND group (p < 0.050). There was no significant difference in diffusion variables between ADWR and ADWOR. In ADWOR, the osteoarthritis group had significantly higher λ3 and lower FA values in the IHLPM than those in the non-osteoarthritis group. CONCLUSION: DTI successfully detected functional changes in the LPM in patients with TMD. The unsynchronized diffusivity changes in the LPM in different subgroups of TMD signified the possibility of using diffusion parameters as indicators to identify the severity of LPM hyperfunction at various stages of TMD.

T1 mapping is useful for staging deep venous thrombosis in the lower extremities.

BACKGROUND: The discrimination of acute and chronic deep venous thrombosis (DVT) is of great importance. Quantitative imaging is an urgent requirement in reflecting intrinsic characteristics of thrombosis. PURPOSE: To investigate the feasibility of T1 mapping in staging DVT in the lower extremities. MATERIAL AND METHODS: A total of 57 patients with DVT in the lower extremities (26 men, 31 women; mean age = 53.3 years) underwent T1-weighted imaging and T1 mapping for obtaining T1 signal intensity (SI) and T1 time of thrombus. The relative SI (rSI) of DVT was obtained by calculating the ratio of thrombus SI to muscle SI. The Mann-Whitney U test was used to compare rSI and T1 time of DVT between acute group (patients with limb edema ≤ 2 weeks) and chronic group (patients with limb edema > 2 weeks). A receiver operator characteristic (ROC) curve was constructed for further evaluation. RESULTS: DVT rSI was significantly higher in the acute group versus the chronic group (2.8 ± 1.2 vs. 1.4 ± 0.6; P<0.05). DVT T1 time was significantly lower in the acute group versus the chronic group (819.4 ± 223.7 ms vs. 1264.8 ± 270.7 ms; P<0.05). The area under the curve (AUC) was 0.93 for T1 time and 0.75 for rSI. When using 1015 ms as the cut-off, the sensitivity and specificity of T1 time were 91% (32/35) and 86% (19/22), respectively. CONCLUSION: T1 mapping is a potential technique in discriminating acute from chronic DVT in the lower extremities and warrants further investigation.

Morphine pretreatment protects against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.

It has been reported that morphine pretreatment (MP) can exert neuroprotective effects, and that protein kinase C (PKC) participates in the initiation and development of ischemic/hypoxic preconditioning in the brain. However, it remains unknown whether PKC is involved in MP-induced neuroprotection. The aim of the present study, which included in vivo and in vitro experiments, was to determine whether the conventional γ isoform of PKC (cPKCγ) was involved in the protective effects of MP against cerebral ischemic injury. The present study included an in vivo experiment using a mouse model of middle cerebral artery occlusion and an in vitro experiment using neuroblastoma N2a cells with oxygen-glucose deprivation (OGD). Furthermore, a cPKCγ antagonist, Go6983, was used to determine the involvement of cPKCγ in the protective effects of MP against cerebral ischemic injury. In the in vivo experiment, neurological deficits, ischemic infarct volume, neural cell damage, apoptosis and caspase-3 activation were evaluated. In the in vitro experiment, flow cytometry was used to determine the activation of caspase-3 in N2a cells with OGD. It was found that MP protected against cerebral ischemic injury. However, intracerebroventricular injection of the cPKCγ antagonist before MP attenuated the neuroprotective effect of MP and increased the activation of cleaved caspase-3. These findings suggested that MP may provide protection against cerebral ischemic injury via a cPKCγ-mediated anti-apoptosis pathway.

SG-LSTM-FRAME: a computational frame using sequence and geometrical information via LSTM to predict miRNA-gene associations.

MOTIVATION: MircroRNAs (miRNAs) regulate target genes and are responsible for lethal diseases such as cancers. Accurately recognizing and identifying miRNA and gene pairs could be helpful in deciphering the mechanism by which miRNA affects and regulates the development of cancers. Embedding methods and deep learning methods have shown their excellent performance in traditional classification tasks in many scenarios. But not so many attempts have adapted and merged these two methods into miRNA-gene relationship prediction. Hence, we proposed a novel computational framework. We first generated representational features for miRNAs and genes using both sequence and geometrical information and then leveraged a deep learning method for the associations' prediction. RESULTS: We used long short-term memory (LSTM) to predict potential relationships and proved that our method outperformed other state-of-the-art methods. Results showed that our framework SG-LSTM got an area under curve of 0.94 and was superior to other methods. In the case study, we predicted the top 10 miRNA-gene relationships and recommended the top 10 potential genes for hsa-miR-335-5p for SG-LSTM-core. We also tested our model using a larger dataset, from which 14 668 698 miRNA-gene pairs were predicted. The top 10 unknown pairs were also listed. AVAILABILITY: Our work can be download in https://github.com/Xshelton/SG_LSTM. CONTACT: luojiawei@hnu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online.

Remimazolam tosilate in upper gastrointestinal endoscopy: A multicenter, randomized, non-inferiority, phase III trial.

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.

A Survey of Regulatory Interactions Among RNA Binding Proteins and MicroRNAs in Cancer.

Recent advances in genomics and proteomics generated a large amount of trans regulatory data such as those mediated by RNA binding proteins (RBPs) and microRNAs. Since many trans regulators target 3' UTR of mRNA transcripts, it is likely that there would be interactions, i.e., competitive or cooperative effect, among these trans factors. We compiled the available RBP and microRNA binding sites, mapped them to the mRNA transcripts, and correlated the binding data with mRNA expression data generated by The Cancer Genome Atlas (TCGA). We separated pairs of RBPs and microRNAs into three scenarios: those that have overlapping target sites on the same mRNA transcript (overlapping), those that have target sites on the same mRNA transcript but non-overlapping (neighboring), and those that do not target the same mRNA transcript (independent). Through a regression analysis on expression profiles, we indeed observed interaction effect between RBPs and microRNAs in the majority of the cancer expression data sets. We further discussed implication of such widespread interactions in the context of cancer and diseases.

High FLT3 Levels May Predict Sorafenib Benefit in Hepatocellular Carcinoma.

PURPOSE: To identify a predictive biomarker of sorafenib for hepatocellular carcinoma personalized therapy. EXPERIMENTAL DESIGN: The patients treated with or without sorafenib after hepatocellular carcinoma recurrence from multicenters were matched with propensity score matching analysis. The expression levels of Fms-like tyrosine kinase 3 (FLT3) in hepatocellular carcinoma specimens of the matched patients (n = 276) were analyzed by IHC. The optimal cut-off point of FLT3 levels for overall survival (OS) was defined via Cutoff Finder. Subgroup analysis of OS was employed to investigate the association between FLT3 levels and sorafenib benefit. The predictive value was assessed via Cox regression models with an interaction term. Hepatocellular carcinoma and paratumoral normal tissues were used to investigate the expression and copy-number variation of FLT3. Patient-derived xenograft (PDX) models were used to confirm the association between FLT3 levels and sorafenib response. RESULTS: Patients with FLT3-high hepatocellular carcinoma exhibited a superior OS upon sorafenib treatment. High FLT3 levels were predictive of sorafenib benefit in terms of OS (P interaction = 0.00006). Copy-number losses and decreased expression of FLT3 in hepatocellular carcinoma were detected in about 64% of patients. Moreover, the PDXs derived from tumors with high FLT3 levels also displayed a better response to sorafenib. CONCLUSIONS: Sorafenib may be able to delay tumor progression in patients with FLT3-high hepatocellular carcinoma. This potential biomarker needs to be further validated in independent cohorts prior to helping stratify patients for precision therapy in advanced hepatocellular carcinoma.

Computational Identification of RNA-Seq Based miRNA-Mediated Prognostic Modules in Cancer.

Systematic identification of miRNA prognostic signature can help decipher the effects of biomarkers in cancer treatment. A number of previous studies have only characterized a single miRNA as a promising prognostic biomarker. There is currently a trend toward combining several miRNAs as a panel of prognostic signatures, but few attempts to explain the mechanism of miRNA combination. Throughout this paper, we refer to "miRNA-mediated prognostic modules" and propose a novel computational approach called ProModule to analyze prognostic biomarkers from the module perspective. ProModule works in two main stages: it first uses univariate and multivariable Cox proportional hazard regressions to find individual miRNA biomarkers and then employs a clustering method to systematically detect miRNA-mediated modules with statistical prognostic significance. We applied ProModule to three data sets in bladder cancer, breast cancer, and liver cancer, and identified several miRNA prognostic modules for each data set. We found that miRNA prognostic modules have more powerful prognostic value than individuals while presenting coherent miRNA-miRNA expression as well as significant functional enrichment, and thus are likely to be biologically meaningful. Availability: ProModule is implemented in R and available at https://github.com/chupan1218/ProModule.

WZ66, a novel acetyl-CoA carboxylase inhibitor, alleviates nonalcoholic steatohepatitis (NASH) in mice.

The global prevalence of nonalcoholic steatohepatitis (NASH) increases incredibly. NASH ends up to advanced liver disease, which is highly threatening to human health. Currently, treatment of NASH is very limited. Acetyl-CoA carboxylases (ACC1/ACC2) are proved as effective drug targets for NASH. We aimed to develop novel ACC inhibitors and evaluate their therapeutic value for NASH prevention. ACC inhibitors were obtained through structure-based drug design, synthesized, screened from ACC enzymatic measurement platform and elucidated in cell culture-based assays and animal models. The lipidome and microbiome analysis were integrated to assess the effects of WZ66 on lipids profiles in liver and plasma as well as gut microbiota in the intestine. WZ66 was identified as a novel ACC1/2 inhibitor. It entered systemic circulation rapidly and could accumulate in liver. WZ66 alleviated NASH-related liver features including steatosis, Kupffer cells and hepatic stellate cells activation in diet-induced obese mice. The triglycerides (TGs) and other lipids including diglycerides (DGs), phosphatidylcholine (PC) and sphingomyelin (SM) were decreased in WZ66-treated mice as evidenced by lipidome analysis in livers. The lipids profiles in plasma were also altered with WZ66 treatment. Plasma TG were moderately increased, while the activation of SREBP1c was not detected. WZ66 also downregulated the abundance of Allobaculum, Mucispirillum and Prevotella genera as well as Mucispirillum schaedleri species in gut microbiota. WZ66 is an ideal lead compound and a potential drug candidate deserving further investigation in the therapeutics of NASH.

Is it dangerous to treat spontaneous intracerebral hemorrhage by minimally invasive surgery plus local thrombolysis in patients with coexisting unruptured intracranial aneurysms?

OBJECTIVES: Limited evidence supports the presumed increased frequency of hemorrhage caused by the unruptured intracranial aneurysms which coexist in patients with spontaneous intracerebral hemorrhage treated with minimally invasive surgery plus local thrombolysis. Subsequently, we sought to determine the safety of local thrombolysis for this particular subset of patients. PATIENTS AND METHODS: We reviewed the medical records of patients treated with minimally invasive surgery plus local thrombolysis for intracerebral hemorrhage between November 2013 to December 2015 in an intensive care unit of a tertiary care hospital. Depending upon the vascular images, unruptured intracranial aneurysms were identified. The primary outcome was any of postoperative intracranial rebleeding. The second outcome included the 30-day death and 6-month follow up graded by Modified Rank Scale. Blind abstractors reviewed the medical data and binary logistic regression was performed to investigate the risk factors of poor prognosis. RESULTS: We identified a cohort of consecutive 188 patients, of whom 23 (12.2%) harbored unruptured intracranial aneurysms. There were 28 aneurysms documented in this study, among which 3 were in the posterior circulation. And in total, 20 (11.3%) cases suffered from postoperative hematoma growth, of which 4 were with aneurysms. Additionally,the 30-day mortality after stroke in patients with aneurysms was 8.69% (2/23), comparable to 13.33% in without (22/165,p = 0.744). The proportion of the favorable outcome at 6-month follow-up in patients with aneurysms was comparable to that in without (47.8% versus 48.5%,p = 1.000) Insignificant associations were demonstrated between the unruptured intracranial aneurysms and postoperative intracranial rehemorrhage (p = 0.092), 30-day death(p = 0.588) and poor long-term prognosis (p = 0.332), respectively. CONCLUSION: Our findings suggest that unruptured intracranial aneurysms seem to represent no increased risks of poor outcome after local thrombolysis for intracerbral hematomas.

BiModule: biclique modularity strategy for identifying transcription factor and microRNA co-regulatory modules.

Systematic identification of gene regulatory modules can provide invaluable knowledge towards understanding aberrant transcriptional/post-transcriptional collaborative regulatory (co-regulatory) effects in cancer. Transcription factor (TF) and microRNA (miRNA) are known as two classes of prominent regulators that play crucial roles in gene regulation. Existing studies on gene regulatory modules identification mainly focused on the miRNA-mediated regulatory network, and few considered these two regulators in a co-occurring network. In this current study, we developed a computational method called BiModule for systematically identifying TF-miRNA co-regulatory modules. BiModule operates in two main stages: it first constructs a cancerspecific regulator-mRNA network and then identifies modules based on maximal bicliques by employing biclique modularity strategy, which is a novel flexible method for bipartite graph mining. We applied our model to a cervical cancer dataset. The results showed that the TF-miRNA co-regulatory modules identified by BiModule exhibit denser connections and stronger expression correlations than another existing related method. Moreover, the BiModule-modules exhibit high biological functional enrichment. In addition, based on Kaplan-Meier survival analysis, we found a number of modules with significant prognostic associations.

Quantitative Analysis of Parotid Gland Secretion Function in Sjögren's Syndrome Patients with Dynamic Magnetic Resonance Sialography.

OBJECTIVE: To evaluate the secretory function of parotid glands by dynamic magnetic resonance (MR) sialography and determine the clinical performance of this technique in diagnosing and evaluating Sjögren's syndrome (SS) patients. MATERIALS AND METHODS: This study enrolled 29 healthy volunteers (25 women and 4 men; mean age, 34.8 ± 6.3 years; age range, 26-47 years) and 25 primary SS (pSS) patients (23 women and 2 men; mean age, 37.7 ± 7.9 years; age range, 25-50 years) with decreased secretory function. The volume of the parotid gland ducts was precisely measured for both groups at single pre- and 6 post-gustatory-stimulated phases. Time-dependent volume change ratio curves were generated, four parameters were derived from the curves: the slope of the increase in the first post-stimulation phase (slope1st), the peak value, the time-to-peak, the total saliva secretion post-stimulation. All values were used to quantitatively evaluate the secretory function of the parotid gland. The repeated measurement analysis, Mann-Whitney U test and receiver operating characteristic curve were applied. RESULTS: Time-dependent volume change ratio curves demonstrated that there is a statistically significant difference between the two groups (F = 8.750; p = 0.005). A quickly increasing curve was shown in the volunteer group, whereas a slowly increasing curve was shown in the pSS patient group. The slope1st, peak value and total saliva secretion post-stimulation of the patient group were significantly lower than those of the volunteer group (p = 0.005, p = 0.003, and p = 0.002, respectively). The time-to-peak between the two groups was not significantly different (p = 0.383). The slope1st can be used as a discriminator to diagnose SS patients (p = 0.015; odds ratio = 4.234; area under the curve = 0.726). CONCLUSION: Dynamic MR sialography is proven to be an effective method in evaluating salivary gland function and has a great potential in diagnosing and evaluating pSS patients.

A Novel Cluster-Based Computational Method to Identify miRNA Regulatory Modules.

The identification of miRNA regulatory modules can help decipher miRNAs combinatorial regulation effects on the pathogenesis underlying complex diseases, especially in cancer. By integrating miRNA/mRNA expression profiles and sequence-based predicted target site information, we develop a novel cluster-based computational method named CoModule for identifying miRNA regulatory modules (MRMs). The ultimate goal of CoModule is to detect the MRMs, in which the miRNAs in each module are expected to present cooperative mechanisms in regulating their targets mRNAs. Here, the co-expression of miRNAs are believed to present cooperative regulatory relationship, therefore, the critical step of CoModule is first to partition the miRNAs with similar expression into a cluster by employing rough set clustering. After gaining credible miRNA clusters, the targets of regulator are naturally added into corresponding clusters to produce the final miRNA regulatory modules. We apply this present method to ovarian cancer datasets and make a comparison with the other two existing prominent approaches. The results indicate that the modules identified by CoModule perform better than the other two methods ranging from the topological aspects to the biological function. Survival analysis detects a number of prognostic modules with statistical significance, which can help reveal the potential diagnostic for ovarian cancer.