Dental complications as a potential indicator of Redondovirus infection: a cross-sectional study.

BACKGROUND: Redondoviridae is a newly discovered virus family linked to oral and respiratory conditions in people, while there is still debate about whether it is also coinfected with other respiratory viruses. This study aimed to determine the frequency of Redondovirus (ReDoV) in nasopharyngeal samples and to investigate any possible links to SARS-CoV-2 infections. METHODS: A polymerase chain reaction (PCR) test was conducted on 731 nasopharyngeal samples from individuals referred to medical centers in Tehran, Iran, for SARS-CoV-2 testing to investigate the prevalence of ReDoV. An oral interview was performed to complete information on dental issues and the individuals' demographics, symptoms, and vaccination history. RESULTS: The prevalence of ReDoV was 25.99%, and 15.26% had a coinfection with SARS-CoV-2. No notable correlation was found regarding ReDoVs and SARS-CoV-2 infections (p > 0.05). Women had a higher ReDoV positivity rate of 18.47% compared to men at 7.52% (p = 0.12), and there was no significant correlation between age groups and ReDoV presence. Nonetheless, a significant association was noted between ReDoVs and dental/gum issues (p < 0.0001, OR: 13.0326). A phylogenetic analysis showed that ReDoVs originated from various human-related clusters. CONCLUSIONS: These results highlight the potential for detecting ReDoVs in nasopharyngeal samples of people with gum or dental issues. Additionally, conducting more ReDoV epidemiological research and proposing oral health as a possible marker for ReDoV infections is important.

Paramagnetic rim lesions predict greater long-term relapse rates and clinical progression over 10 years.

BACKGROUND: Paramagnetic rim lesions (PRLs) have been linked to higher clinical disease severity and relapse frequency. However, it remains unclear whether PRLs predict future, long-term disease progression. OBJECTIVES: The study aimed to assess whether baseline PRLs were associated with subsequent long-term (10 years) Expanded Disability Status Scale (EDSS) increase and relapse frequency and, if so, whether PRL-associated EDSS increase was mediated by relapse. METHODS: This retrospective analysis included 172 people with multiple sclerosis (pwMS) with 1868 yearly clinical visits over a mean follow-up time of 10.2 years. 3T magnetic resonance imaging (MRI) was acquired at baseline and PRLs were assessed on quantitative susceptibility mapping (QSM) images. The associations between PRLs, relapse, and rate of EDSS change were assessed using linear models. RESULTS: PRL+ pwMS had greater overall annual relapse rate (ß = 0.068; p = 0.010), three times greater overall odds of relapse (exp(ß) = 3.472; p = 0.009), and greater rate of yearly EDSS change (ß = 0.045; p = 0.010) than PRL- pwMS. Greater PRL number was associated with greater odds of at least one progression independent of relapse activity (PIRA) episode over follow-up (exp(ß) = 1.171, p = 0.009). Mediation analysis showed that the association between PRL presence (yes/no) and EDSS increase was 96.7% independent of relapse number. CONCLUSION: PRLs are a marker of aggressive ongoing disease inflammatory activity, including more frequent future clinical relapses and greater long-term, relapse-independent disability progression.

A New Case of Granulomatosis with Polyangiitis Presented with Tolosa-Hunt Syndrome Manifestations.

Background: Tolosa-Hunt syndrome (THS) is a rare disorder involving the orbital and retro-orbital space. The typical symptoms include sensory loss in the trigeminal nerve's distribution, orbital pain, swelling, headaches, and cranial nerve palsies. Case Presentation. We report a 40-year-old female who initially presented with biparietal headache, unresponsive to medication, which then led to ophthalmoplegia and orbital pain. Serological findings demonstrated positive CANCA-PR3. She was initially treated with 1 g pulse methylprednisolone for three days. Based on the rheumatological evaluation and her positive lung nodule, hematuria, dysmorphic red blood cells, and positive antiproteinase 3 classic antineutrophil cytoplasm antibodies (CANCA-PR3) and also based on the diagnostic criteria for granulomatosis with polyangiitis criteria for Wegner disease, her treatment was continued with prednisolone 1 mg/kg and also rituximab at the first and 14th day of treatment. Conclusion: In our case of THS, we achieved satisfactory improvement in symptoms through the administration of high-dose steroids.

New-onset ANCA-associated vasculitis presenting with neuropathy after COVID-19 infection: A case report and literature review.

Coronavirus Disease 2019 (COVID-19) is a viral infection caused by SARS-CoV-2, which can trigger autoimmune diseases such as antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis (AAV) that affect small and medium-sized blood vessels in multiple organs. This study discusses a case with neuropathy and positive ANCA after COVID-19 infection and reviews the literature on AAV following COVID-19 infection. A 59-year-old man is presented that was referred to Shariati Hospital for evaluation of neurologic problems after a COVID-19 infection. Initially, he had flu-like symptoms. A few days later, he developed right distal upper and lower limb paresthesia. His electromyography (EMG) and nerve conduction velocity (NCV) results were consistent with polyneuropathy. Lumbar puncture (LP) was normal except for positive COVID-19 polymerase chain reaction (PCR). The patient's paresthesia worsened. Laboratory data showed leukocytosis, anemia, thrombocytosis, high erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Perinuclear anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive. According to the results, vasculitis was the main differential diagnosis. The sural nerve biopsy was performed, and the result was consistent with small to medium-sized vessel vasculitis. The patient was diagnosed with COVID-induced AAV. He was prescribed methylprednisolone and cyclophosphamide and was discharged with prednisolone and cotrimoxazole. In this study, a unique case of AAV induced by COVID-19 infection confirmed by nerve biopsy is presented. A review of the literature found 48 cases of new-onset AAV in adults and pediatrics after COVID-19 infection. Further research is needed to completely understand the relationship between COVID-19.

Evaluation of INI1 Protein Expression Through IHC Study in Pediatric High-Grade Brain Tumors in South of Iran in 2008-2021.

Background & Objective: Brain tumors are the most frequent solid tumors in children. High-grade tumors are more challenging in diagnosis. Atypical teratoid rhabdoid tumor (ATRT) may be mistaken for other high-grade brain tumors. Molecular genetic analysis of ATRT has shown deletion and mutation in the hSNF5/INI1 gene in most of the cases. The INI1 protein expression can be helpful for the accurate diagnosis. Methods: In this study, immunohistochemical staining (IHC) using INI1 antibody was performed to determine the possibility of ATRT misdiagnosis. Totally, 147 tumors including 6 ATRTs, 81 medulloblastomas, and 60 other CNS tumors were examined in children between 0 and 17 years old. Results: No nuclear staining was found in the six ATRT cases, while most of other CNS tumors demonstrated nuclear staining. Five cases were previously diagnosed with medulloblastoma, primitive neuroectodermal tumor (PNET), and anaplastic oligodendroglioma, while the diagnoses were changed to ATRT based on the re-evaluation of the H&E slides and INI1 study. Additionally, two cases were recurrent tumors whose features were consistent with those of ATRT. The INI1 immunostaining was negative in these cases. Conclusion: INI1 was very helpful in distinguishing ATRT from its mimickers in challenging cases. All known ATRT cases in this study were immunonegative for INI1. Thus, INI1 is recommended to be used in the initial IHC panel for the high-grade brain tumors, especially in children under the age of three years, so that they can benefit from intensified therapeutic regimens.

Reliability of paramagnetic rim lesion classification on quantitative susceptibility mapping (QSM) in people with multiple sclerosis: Single-site experience and systematic review.

BACKGROUND: Recent developments in iron-sensitive MRI techniques have enabled visualization of chronic active lesions as paramagnetic rim lesions (PRLs) in vivo. Although PRLs have potential as a diagnostic and prognostic tool for multiple sclerosis (MS), limited studies have reported the reliability of PRL assessment. Further evaluation of PRL reliability, through original investigations and review of PRL literature, are warranted. METHODS: A single-center cohort study was conducted to evaluate the inter-rater reliability of PRL identification on quantitative susceptibiltiy mapping (QSM) in 10 people with MS, 5 people with clinically isolated syndrome, and 5 healthy controls. An additional systematic literature search was then conducted of published PRL reliability data, and these results were synthesized. RESULTS: In the single-center study, both inter-rater and intra-rater reliability of per-subject PRL number were at an "Excellent" (intraclass correlation coefficient (ICC) of 0.901 for both) level with only 2-years lesion classification experience. Across the reported literature values, reliability of per-lesion rim presence was on average "Near perfect" (for intra-rater; Cohen's κ = 0.833) and "Substantial" (for inter-rater; Cohens κ = 0.687), whereas inter-rater reliability of per-subject PRL number was "Good" (ICC = 0.874). Only 4/22 studies reported complete information on rater experience, rater level of training, detailed PRL classification criteria, and reliability cohort size and disease subtypes. CONCLUSION: PRLs can be reliably detected both at per-lesion and per-subject level. We recommend that future PRL studies report detailed reliability results, including rater experience level, and use a standardized set of reliability metrics (Cohen's κ or ICC) for improved comparability between studies.

Alternation in functional connectivity within default mode network after psychodynamic psychotherapy in borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by impairments in emotion regulation, impulse control, and interpersonal and social functioning along with a deficit in emotional awareness and empathy. In this study, we investigated whether functional connectivity (FC) within the default mode network (DMN) is affected by 1-year psychodynamic psychotherapy in patients with BPD. METHODS: Nine BPD patients filled out the demography, Interpersonal Reactive Index (IRI), Toronto Alexithymia Scale 20 (TAS 20), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and the Borderline Evaluation Severity over Time (BEST) questionnaire. The BPD group (9F) and the control group (9F) had a mean ± SD age of 28.2 ± 5.3 years and 30.4 ± 6.1 years, respectively. BPD subjects underwent longitudinal resting-state fMRI before psychodynamic psychotherapy and then every 4 months for a year after initiating psychotherapy. FC in DMN was characterized by calculating the nodal degree, a measure of centrality in the graph theory. RESULTS: The results indicated that patients with BPD present with aberrant DMN connectivity compared to healthy controls. Over a year of psychotherapy, the patients with BPD showed both FC changes (decreasing nodal degree in the dorsal anterior cingulate cortex and increasing in other cingulate cortex regions) and behavioral improvement in their symptoms and substance use. There was also a significant positive association between the decreased nodal degree in regions of the dorsal cingulate cortex and a decrease in the score of the TAS-20 indicating difficulty in identifying feelings after psychotherapy. CONCLUSION: In BPD, there is altered FC within the DMN and disruption in self-processing and emotion regulation. Psychotherapy may modify the DMN connectivity and that modification is associated with positive changes in BPD emotional symptoms.

Anti-Infective and Toxicity Properties of Carbon Based Materials: Graphene and Functionalized Carbon Nanotubes.

Recently, antimicrobial activities of various carbon-based nanomaterials against specific pathogens have become one of the most significant research interests in this field. Carbon nanotubes (CNTs) are promising multidisciplinary nanostructures in biomedicine, drug delivery, genetic engineering, biosensors, and artificial implants. However, the biomedical administration of CNTs is dependent on their solubility, toxicity, and biocompatibility, as well as novel drug-delivery applications through optimization of the drug's loading capacity, cellular absorption, and continuous release within the target cell. The usage of CNTs and Graphene materials as antimicrobial agents and nanocarriers for antibiotics delivery would possibly improve their bioavailability and facilitate better anti-infective therapy. However, it is worth mentioning that CNTs' antimicrobial activity and toxicity are highly dependent on their preparation and synthesis method. Various types of research have confirmed that diameter, length, residual catalyst, metal content, surface coating, electronic structure, and dispersibility would affect CNTs' toxicity toward bacteria and human cells. In this review article, a general study was performed on the antimicrobial properties of carbon-based nanomaterials, as well as their toxicity and applications in confronting different microorganisms. This study could be useful for researchers who are looking for new and effective drug delivery methods in the field of microbial resistance.

Extraction of discriminative features from EEG signals of dyslexic children; before and after the treatment.

Dyslexia is a neurological disorder manifested as difficulty reading and writing. It can occur despite adequate instruction, intelligence, and intact sensory abilities. Different electroencephalogram (EEG) patterns have been demonstrated between dyslexic and healthy subjects in previous studies. This study focuses on the difference between patients before and after treatment. The main goal is to identify the subset of features that adequately discriminate subjects before and after a specific treatment plan. The treatment consists of Transcranial Direct Current Stimulation (tDCS) and occupational therapy using the BrainWare SAFARI software. The EEG signals of sixteen dyslexic children were recorded during the eyes-closed resting state before and after treatment. The preprocessing step was followed by the extraction of a wide range of features to investigate the differences related to the treatment. An optimal subset of features extracted from recorded EEG signals was determined using Principal Component Analysis (PCA) in conjunction with the Sequential Floating Forward Selection (SFFS) algorithm. The results showed that treatment leads to significant changes in EEG features like spectral and phase-related EEG features, in various regions. It has been demonstrated that the extracted subset of discriminative features can be useful for classification applications in treatment assessment. The most discriminative subset of features could classify the data with an accuracy of 92% with SVM classifier. The above result confirms the efficacy of the treatment plans in improving dyslexic children's cognitive skills.

Brain functional connectivity analysis in patients with relapsing-remitting multiple sclerosis: A graph theory approach of EEG resting state.

Multiple sclerosis (MS) is an autoimmune disease related to the central nervous system (CNS). This study aims to investigate the effects of MS on the brain's functional connectivity network using the electroencephalogram (EEG) resting-state signals and graph theory approach. Resting-state eyes-closed EEG signals were recorded from 20 patients with relapsing-remitting MS (RRMS) and 18 healthy cases. In this study, the prime objective is to calculate the connectivity between EEG channels to assess the differences in brain functional network global features. The results demonstrated lower cortical activity in the alpha frequency bands and higher activity for the gamma frequency bands in patients with RRMS compared to the healthy group. In this study, graph metric calculations revealed a significant difference in the diameter of the functional brain network based on the directed transfer function (DTF) measure between the two groups, indicating a higher diameter in RRMS cases for the alpha frequency band. A higher diameter for the functional brain network in MS cases can result from anatomical damage. In addition, considerable differences between the networks' global efficiency and transitivity based on the imaginary part of the coherence (iCoh) measure were observed, indicating higher global efficiency and transitivity in the delta, theta, and beta frequency bands for RRMS cases, which can be related to the compensatory functional reaction from the brain. This study indicated that in RRMS cases, some of the global characteristics of the brain's functional network, such as diameter and global efficiency, change and can be illustrated even in the resting-state condition when the brain is not under cognitive load.

Significant Effect of Crocin on the Gene Expression of MicroRNA-21 and MicroRNA-155 in Patients with Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis associated with gradual joint destruction. The current treatment aims to alleviate pain and inflammation and improve the quality of life. Crocin is an active ingredient in saffron, with anti-inflammatory properties. MicroRNAs are small, non-coding RNAs that regulate gene expression. We aimed to evaluate the effect of crocin on the gene expression of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 in OA patients and compare it with a placebo. This study was approved and registered in the Iranian Registry of Clinical Trials (2015021910507N2) and ClinicalTrials.gov identifier: NCT03375814. Forty OA patients were randomly divided into two equal groups, receiving either crocin or placebo. Peripheral blood samples were collected before and four months after the intervention. The pain was assessed using the visual analog scale, and laboratory tests included C-reactive protein and erythrocyte sedimentation rate. The expression levels of microRNA-146a, microRNA-155, microRNA-223, and microRNA-21 genes were evaluated by SYBR Green real-time PCR. The results showed that the gene expression levels of microRNA-21 and microRNA-155 in patients receiving crocin were significantly decreased and increased, respectively. No significant changes were observed in microRNA-146a and microRNA-223 gene expression levels. In conclusion, crocin's anti-inflammatory role might be partly attributed to its effects on the gene expression of microRNA-21 and microRNA-155.

A Nonlinear Effective Connectivity Measure Based on Granger Causality and Volterra Series.

Estimating effective connectivity, especially in brain networks, is an important topic to find out the brain functions. Various effective connectivity measures are presented, but they have drawbacks, including bivariate structure, the problem in detecting nonlinear interactions, and high computational cost. In this paper, we have proposed a novel multivariate effective connectivity measure based on a hierarchical realization of the Volterra series model and Granger causality concept, namely hierarchical Volterra Granger causality (HVGC). HVGC is a multivariate connectivity measure that can detect linear and nonlinear causal effects. The performance of HVGC is compared with Granger causality index (GCI), conditional Granger causality index (CGCI), transfer entropy (TE), phase transfer entropy (Phase TE), and partial transfer entropy (Partial TE) in simulated and physiological datasets. In addition to accuracy, specificity, and sensitivity, the Matthews correlation coefficient (MCC) is used to evaluate the connectivity estimation in simulated datasets. Furthermore influence of different SNRs is investigated on the estimated connectivity. The obtained results show that HVGC with a minimum MCC of 0.76 performs well in the detection of both linear and nonlinear interactions in simulated data. HVGC is also applied to a physiological dataset that was cardiorespiratory interaction signals recorded during sleep from a patient suffering from sleep apnea. The results of this dataset also demonstrate the capability of the proposed method in the detection of causal interactions. Applying HVGC on the simulated fMRI dataset led to a high MCC of 0.78. Moreover, the results indicate that HVGC has slight changes in different SNRs. The results indicate that HVGC can estimate the causal effects of a linear and nonlinear system with a low computational cost and it is slightly affected by noise.

Semi-Synthesis of New 1,2,3-Triazole Derivatives of 9-Bromonoscapine and their Anticancer Activities.

Novel 1,2,3-triazole-tethered 9-bromonoscapine derivatives were synthesized by the propargylation of N-nornoscapine followed by Huisgen's 1,3-dipolar cycloaddition of the terminal alkynes with different azides. Cytotoxicity of the products was studied by MTT assay against the MCF-7 breast cancer cell line. Most of the compounds revealed a better cytotoxicity than N-nornoscapine and 9-bromonornoscapine as the parent compounds. Among the synthesized compounds, those with a hydroxylated aliphatic side chain (5p, 5q, and 5r) showed the highest activities (IC50s: 47.2, 37.9, and 32.3 µg/mL, respectively). Molecular docking studies showed that these compounds also had the highest docking scores and effective interactions with binding sites equal to -8.074, -7.425 and -7.820 kcal/mol, respectively.

Multiple sclerosis reduces synchrony of the magnocellular pathway.

Multiple Sclerosis (MS) is an autoimmune demyelinating disease that damages the insulation of nerve cell fibers in the brain and spinal cord. In the visual system, this demyelination results in a robust delay of visually evoked potentials (VEPs), even in the absence of overt clinical symptoms such as blurred vision. VEPs, therefore, offer an avenue for early diagnosis, monitoring disease progression, and, potentially, insight into the differential impairment of specific pathways. A primary hypothesis has been that visual stimuli driving the magno-, parvo-, and konio-cellular pathways should lead to differential effects because these pathways differ considerably in terms of myelination. Experimental tests of this hypothesis, however, have led to conflicting results. Some groups reported larger latency effects for chromatic stimuli, while others found equivalent effects across stimulus types. We reasoned that this lack of pathway specificity could, at least in part, be attributed to the relatively coarse measure of pathway impairment afforded by the latency of a VEP. We hypothesized that network synchrony could offer a more sensitive test of pathway impairments. To test this hypothesis, we analyzed the synchrony of occipital electroencephalography (EEG) signals during the presentation of visual stimuli designed to bias activity to one of the three pathways. Specifically, we quantified synchrony in the occipital EEG using two graph-theoretic measures of functional connectivity: the characteristic path length (L; a measure of long-range connectivity) and the clustering coefficient (CC; a measure of short-range connectivity). Our main finding was that L and CC were both smaller in the MS group than in controls. Notably, this change in functional connectivity was limited to the magnocellular pathway. The effect sizes (Hedge's g) were 0.89 (L) and 1.26 (CC) measured with magno stimuli. Together, L and CC define the small-world nature of a network, and our finding can be summarized as a reduction in the small-worldness of the magnocellular network. We speculate that the reduced efficiency of information transfer associated with a reduction in small-worldness could underlie visual deficits in MS. Relating these measures to differential diagnoses and disease progression is an important avenue for future work.

Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library.

Noscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z' > 0.7). The screening resulted in the identification of two novel noscapine derivatives as inhibitors of MDA cell growth with IC50 values of 5 µM and 1.5 µM, respectively. Both hit molecules have a five-fold and seventeen-fold higher potency, compared with that of lead compound noscapine (IC50 26 µM). The identified active derivatives retain the tubulin-binding ability of noscapine. Further testing of both hit molecules, alongside the natural product against additional cancer cell lines (HepG2, HeLa and PC3 cells) confirmed our initial findings. Both molecules have improved anti-proliferative properties when compared to the initial natural product, noscapine.

Adrenocortical adenoma with myelolipomatous metaplasia: a potential diagnostic pitfall: a case report and review of the literature.

BACKGROUND: Adrenal incidentalomas are often found during investigation for another tumor or unrelated problems. Except for adrenal myelolipoma (second most common primary adrenal incidentaloma following adrenocortical adenomas), adrenal lipomatous tumors are uncommon generally and are often described as case reports in the literature. Since the amount of fat is variable, without the help of advanced imaging techniques, some adrenal lipomatous tumors may be misdiagnosed before pathologic examination. Herein, we report a case of adrenal adenoma with myelolipomatous metaplasia that was excised as a periceliac mass in the setting of recurrent pancreatic cyst. CASE REPORT: A 45-year-old Iranian woman with hypertension and end-stage renal disease presented with recurrence of a pancreatic cyst (previous pathologic report was mucinous cyst adenoma). During exploratory laparotomy, the mentioned pancreatic cyst was tightly attached to the stomach and jejunum. There was also a periceliac round rubbery lesion (firstly diagnosed by endoscopic ultrasound) that was excised for ruling out malignancy. Histologic examination of the periceliac mass was found to be adrenocortical adenoma with foci of myelolipomatous metaplasia. The pancreatic cyst histology was just a pseudocyst. CONCLUSION: Our case highlights the significance of complete evaluation of incidental findings before surgical intervention, even in the setting of another primary tumor. Myelolipoma and myelolipomatous change (metaplasia) are two different entities. Although very similar as to pathogenesis, there are still some differences.

High- Versus Low-Molecular-Weight Hyaluronic Acid for the Treatment of Rotator Cuff Tendinopathy: A Triple-Blind Randomized Comparative Trial.

BACKGROUND: Shoulder pain most commonly originates from the tendon structures of the rotator cuff. OBJECTIVE: We compared the clinical effects of high- versus low-molecular-weight (LMW) hyaluronic acid for the management of rotator cuff tendinopathy. METHODS: We carried out a parallel, triple-blind, randomized comparative trial at a teaching hospital. In total, 56 patients aged 16 to 70 years with rotator cuff tendinopathy were randomly allocated to 2 groups. We administered a single shoulder injection of either 1 mL of 1% high- (>2000 kDa) or 1 mL of 1% LMW hyaluronate (500-700 kDa) to the corresponding groups. The primary outcome was the intensity of shoulder pain. The secondary outcomes were range of motion and disability of the shoulder, and quality of life. We performed the measurements at baseline and at 1, 4, and 12 weeks postintervention. The pain measurements were repeated at the sixth month postintervention. RESULTS: Comparisons of baseline versus 3 months showed that both interventions were beneficial in the management of the tendinopathy (all P values <0.05). However, between-group analyses did not indicate any clinically significant difference between the 2 medications. The pain, induration (P = 0.007), and inflammation at the site of the injection were less prominent for LMW hyaluronate. CONCLUSION AND RELEVANCE: Both medications are effective for the treatment of tendinopathy. The benefits last at least for 3 months, and pain alleviation lasts partially for 6 months. The shoulder injection of LMW hyaluronate is more tolerable to the patient. Therefore, we recommend LMW hyaluronate as the first choice for the management of rotator cuff tendinopathy.

An Adaptive Kalman Filter Bank for ECG Denoising.

Model-based Bayesian frameworks proved their effectiveness in the field of ECG processing. However, their performances rely heavily on the pre-defined models extracted from ECG signals. Furthermore, their performances decrease substantially when ECG signals do not comply with their models- a situation generally occurs in the case of arrhythmia-. In this paper, we propose a novel Bayesian framework based on Kalman filter, which does not need a predefined model and can adapt itself to different ECG morphologies. Compared with the previous Bayesian techniques, the proposed method requires much less preprocessing and it only needs to know the location of R-peaks to start ECG processing. Our method uses a filter bank comprised of two adaptive Kalman filters, one for denoising QRS complex (high frequency section) and another one for denoising P and T waves (low frequency section). The parameters of these filters are estimated and iteratively updated using expectation maximization (EM) algorithm. In order to deal with nonstationary noises such as muscle artifact (MA) noise, we used Bryson and Henrikson's technique for the prediction and update steps inside the Kalman filter bank. We evaluated the performance of the proposed method on different ECG databases containing signals having morphological changes and abnormalities such as atrial premature complex (APC), premature ventricular contractions (PVC), Ventricular Tachyarrhythmia (VT) and sudden cardiac death (SCD). The proposed algorithm was compared with several popular ECG denoising methods such as wavelet transform (WD) and empirical mode decomposition (EMD). The comparison results showed that the proposed method performs well in the presence of various ECG morphologies in both stationary and non-stationary environments especially at low input SNRs.

Discovery of noscapine derivatives as potential ß-tubulin inhibitors.

Twenty novel 1,2,3-triazole noscapine derivatives were synthesized starting from noscapine by consecutive N-demethylation, reduction of lactone ring, N-propargylation and Huisgen 1,3-dipolar cycloaddition reaction. In order to select the most promising molecules to subject to further biophysical and biological evaluation, a molecular docking analysis round was performed using noscapine as reference compound. The molecules featuring docking predicted binding affinity better than that of noscapine were then subjected to MTT assay against MCF7 cell line. The obtained results disclosed that all the selected triazole derivatives exhibited a remarkably lower cell viability compared to noscapine in the range of 20 µM in 48 h. In an attempt to correlate the biological activity with the ability to bind tubulin, the surface plasmon resonance (SPR) assay was employed. Compounds 8a, 8h, 9c, 9f and 9j were able to bind tubulin with affinity constant values in the nanomolar range and higher if compared to noscapine. Integrating computational predictions and experimental evaluation, two promising compounds (8h and 9c) were identified, whose relevant cytotoxicity was supposed to be correlated with tubulin binding affinity. These findings shed lights onto structural modifications of noscapine toward the identification of more potent cytotoxic agents targeting tubulin.

Graph theory analysis of directed functional brain networks in major depressive disorder based on EEG signal.

OBJECTIVE: Analysis of functional and structural brain networks has suggested that major depressive disorder (MDD) is associated with a disruption in brain networks. This paper aims to investigate the abnormalities of brain networks in MDD. APPROACH: To this aim, we constructed weighted directed functional networks based on electroencephalography (EEG) signals of 26 MDD patients and 23 normal (N) subjects. The nodes of networks were 19 EEG electrodes, and the edges were phase transfer entropy (PTE) between each pair of electrodes. PTE is a model-free, phase-based effective connectivity measure that is relatively robust to noise and linear mixing. Since the correct instantaneous phase of a signal is computed for narrow frequency bands, the networks were analyzed in eight frequency sub-bands including delta, theta, alpha1, alpha2, beta1, beta2, beta3, and beta4. To assess the alteration in the topology of brain networks in MDD patients, graph theory metrics consisting of global efficiency, local efficiency, node betweenness centrality, node degree, and node strength were analyzed by statistical tests and classification. Furthermore, directed differential connectivity graphs (dDCGs) for the MDD and N groups were studied. MAIN RESULTS: These analyses revealed a higher node degree and strength in the dDCGs of the MDD group than the normal group. It was also found that MDD brain networks have a more randomized structure than the N group. Moreover, our results indicated that the out-degree of networks classified MDD and N subjects with an accuracy of 92%; thus, our method can be considered as a powerful tool for depression detection. SIGNIFICANCE: Our analysis may provide new insights into developing biomarkers for depression detection based on brain networks.