Search results for: deep brain stimulation

Authors: I. Wardana Ketut, I. Suparwa Nyoman

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This study investigated the form and characteristic of speech sound produced by three Balinese subjects who have recovered from aphasia as well as intervened their language impairment on side of linguistic and neuronal aspects of views. The failure of judging the speech sound was caused by impairment of motor cortex that indicated there were lesions in left hemispheric language zone. Sound articulation phenomena were in the forms of phonemes deletion, replacement or assimilation in individual words and meaning building for anomic aphasia. Therefore, the Balinese sound patterns were stimulated by showing pictures to the subjects and recorded to recognize what individual consonants or vowels they unclearly produced and to find out how the sound disorder occurred. The physiology of sound production by subject’s speech organs could not only show the accuracy of articulation but also any level of severity the lesion they suffered from. The subjects’ speech sounds were investigated, classified and analyzed to know how poor the lingual units were and observed to clarify weaknesses of sound characters occurred either for place or manner of articulation. Many fricative and stopped consonants were replaced by glottal or palatal sounds because the cranial nerve, such as facial, trigeminal, and hypoglossal underwent impairment after the stroke. The phonological intervention was applied through a technique called phonemic articulation drill and the examination was conducted to know any change has been obtained. The finding informed that some weak articulation turned into clearer sound and simple meaning of language has been conveyed. The hierarchy of functional parts of brain played important role of language formulation and processing. From this finding, it can be clearly emphasized that this study supports the role of right hemisphere in recovery from aphasia is associated with functional brain reorganization.

Keywords: aphasia, intervention, phonology, stroke

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Authors: Neşe Işık, Şenol Altıok, Galip Devrim Eryılmaz, Aydın durukan, Hasan Özgür Daş

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In this study, an active landslide zone affecting the road alignment on the Tortum-Uzundere (Erzurum/Turkey) highway was investigated. Due to the landslide movement, problems have occurred in the existing road pavement, which has caused both safety problems and reduced driving comfort in the operation of the road. In order to model the landslide, drilling, geophysical and inclinometer studies were carried out in the field within the scope of ground investigation. Laboratory tests were carried out on soil and rock samples obtained from the borings. When the drilling and geophysical studies were evaluated together, it was determined that the study area has a complex geological structure. In addition, according to the inclinometer results, the direction and speed of movement of the landslide mass were observed. In order to create an idealized geological profile, all field and laboratory studies were evaluated together and then the sliding surface of the landslide was determined by back analysis method. According to the findings obtained, it was determined that the landslide was massively large, and the movement occurred had a deep sliding surface. As a result of the numerical analyses, it was concluded that the Slope angle reduction is the most economical and environmentally friendly method for the control of the landslide mass.

Keywords: landslide, geotechnical methods, geophysics, monitoring, highway

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Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

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Authors: Hamidreza Torabi, Mohsen Moghtaderi

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Introduction: Currently, deep vitrectomy with silicone oil tamponade is the standard treatment method for patients with Rhegmatogenous Retinal Detachment (RRD). After retinal repair, it is necessary to remove silicone oil from the eye, but the appropriate time to remove the oil and complications related to that time has been less studied. The aim of this study was to compare the results of the early removal of silicone oil with the delayed removal of silicone oil in patients with RRD. Method & material: Patients who were referred to the Ophthalmology Clinic of Baqiyatallah Hospital, Tehran, Iran, due to RRD with detached macula in 2021 & 2022 were evaluated. These patients were treated with deep vitrectomy and silicone oil tamponade. Patients whose retinas were attached after the passage of time were candidates for silicone oil removal (SOR) surgery. For patients in the early SOR group, SOR surgery was performed 3-6 months after the initial vitrectomy surgery, and for the late SOR group, SOR was performed after 6 months after the initial vitrectomy surgery. Results: In this study, 60 patients with RRD were evaluated. 23 (38.3%) patients were in the early group, and 37 (61.7%) patients were in the late group. Based on our findings, it was seen that the mean visual acuity of patients based on the Snellen chart in the early group (0.48 ± 0.23 Decimal) was better than the late group (0.33 ± 0.18 Decimal) (P-value=0.009). Retinal re-detachment has happened only in one patient with early SOR. Conclusion: Early removal of silicone oil (less than 6 months) from the eyes of patients undergoing RRD surgery has been associated with better vision results compared to late removal.

Keywords: retinal detachment, vitrectomy, silicone oil, silicone oil removal, visual acuity

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Authors: Jean Marriz M. Manzano, Marc D. Rosales, Magdaleno R. Vasquez Jr., Maria Theresa G. De Leon

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This paper discusses the effects of surface roughness on a cantilever beam vibrational energy harvester. A silicon sample was fabricated using MEMS fabrication processes. When etching silicon using deep reactive ion etching (DRIE) at large etch depths, rougher surfaces are observed as a result of increased response in process pressure, amount of coil power and increased helium backside cooling readings. To account for the effects of surface roughness on the characteristics of the cantilever beam, finite element method (FEM) modeling was performed using actual roughness data from fabricated samples. It was found that when etching about 550um of silicon, root mean square roughness parameter, Sq, varies by 1 to 3 um (at 100um thick) across a 6-inch wafer. Given this Sq variation, FEM simulations predict an 8 to148 Hz shift in the resonant frequency while having no significant effect on the output power. The significant shift in the resonant frequency implies that careful consideration of surface roughness from fabrication processes must be done when designing energy harvesters.

Keywords: deep reactive ion etching, finite element method, microelectromechanical systems, multiphysics analysis, surface roughness, vibrational energy harvester

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Authors: Celso L. Fernando, Toshio Yoshii, Takahiro Tsubota

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Understanding the causes of a road accident and predicting their occurrence is key to preventing deaths and serious injuries from road accident events. Traditional statistical methods such as the Poisson and the Logistics regressions have been used to find the association of the traffic environmental factors with the accident occurred; recently, an artificial neural network, ANN, a computational technique that learns from historical data to make a more accurate prediction, has emerged. Although the ability to make accurate predictions, the ANN has difficulty dealing with highly unbalanced attribute patterns distribution in the training dataset; in such circumstances, the ANN treats the minority group as noise. However, in the real world data, the minority group is often the group of interest; e.g., in the road traffic accident data, the events of the accident are the group of interest. This study proposes a combination of the k-means with the ANN to improve the predictive ability of the neural network model by alleviating the effect of the unbalanced distribution of the attribute patterns in the training dataset. The results show that the proposed method improves the ability of the neural network to make a prediction on a highly unbalanced distributed attribute patterns dataset; however, on an even distributed attribute patterns dataset, the proposed method performs almost like a standard neural network.

Keywords: accident risks estimation, artificial neural network, deep learning, k-mean, road safety

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Authors: Feng Yang

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Machine learning (ML), especially deep learning (DL), has been extensively applied to many applications in recently years and gained great success in solving different problems, including scientific problems. However, conventional ML/DL methodologies are purely data-driven which have the limitations, such as need of ample amount of labelled training data, lack of consistency to physical principles, and lack of generalizability to new problems/domains. Recently, there is a growing consensus that ML models need to further take advantage of prior knowledge to deal with these limitations. Physics-informed machine learning, aiming at integration of physics/domain knowledge into ML, has been recognized as an emerging area of research, especially in the recent 2 to 3 years. In this work, physics-informed ML, specifically physics-informed neural network (NN), is employed and implemented to estimate the displacements at x, y, z directions in a solid mechanics problem that is controlled by equilibrium equations with boundary conditions. By incorporating the physics (i.e. the equilibrium equations) into the learning process of NN, it is showed that the NN can be trained very efficiently with a small set of labelled training data. Experiments with different settings of the NN model and the amount of labelled training data were conducted, and the results show that very high accuracy can be achieved in fulfilling the equilibrium equations as well as in predicting the displacements, e.g. in setting the overall displacement of 0.1, a root mean square error (RMSE) of 2.09 × 10−4 was achieved.

Keywords: deep learning, neural network, physics-informed machine learning, solid mechanics

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Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri

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Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.

Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation

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Authors: Shaira L. Kee, Michael Aaron G. Sy, Myles Joshua T. Tan, Hezerul Abdul Karim, Nouar AlDahoul

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Skin diseases are considered the fourth most common disease, with melanoma and non-melanoma skin cancer as the most common type of cancer in Caucasians. The alarming increase in Skin Cancer cases shows an urgent need for further research to improve diagnostic methods, as early diagnosis can significantly improve the 5-year survival rate. Machine Learning algorithms for image pattern analysis in diagnosing skin lesions can dramatically increase the accuracy rate of detection and decrease possible human errors. Several studies have shown the diagnostic performance of computer algorithms outperformed dermatologists. However, existing methods still need improvements to reduce diagnostic errors and generate efficient and accurate results. Our paper proposes an ensemble method to classify dermoscopic images into benign and malignant skin lesions. The experiments were conducted using the International Skin Imaging Collaboration (ISIC) image samples. The dataset contains 3,297 dermoscopic images with benign and malignant categories. The results show improvement in performance with an accuracy of 88% and an F1 score of 87%, outperforming other existing models such as support vector machine (SVM), Residual network (ResNet50), EfficientNetB0, EfficientNetB4, and VGG16.

Keywords: deep learning - VGG16 - efficientNet - CNN – ensemble – dermoscopic images - melanoma

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Authors: Tatiana N. Astakhova, Alexander E. Saprygin, Tatyana A. Golovko, Alexander N. Savostyanov, Mikhail S. Vlasov, Natalia V. Borisova, Alexandera G. Karpova, Urana N. Kavai-ool, Elena D. Mokur-ool, Nikolay A. Kolchanov, Lubomir I. Aftanas

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The aim of the study is to compare behaviorally and EEG reactions in Turkic-speaking inhabitants of Siberia (Tuvinians and Yakuts) and Russians during the recognition of syntax errors in native and foreign languages. 63 healthy aboriginals of the Tyva Republic, 29 inhabitants of the Sakha (Yakutia) Republic, and 55 Russians from Novosibirsk participated in the study. All participants completed a linguistic task, in which they had to find a syntax error in the written sentences. Russian participants completed the task in Russian and in English. Tuvinian and Yakut participants completed the task in Russian, English, and Tuvinian or Yakut, respectively. EEG’s were recorded during the solving of tasks. For Russian participants, EEG's were recorded using 128-channels. The electrodes were placed according to the extended International 10-10 system, and the signals were amplified using ‘Neuroscan (USA)’ amplifiers. For Tuvinians and Yakuts EEG's were recorded using 64-channels and amplifiers Brain Products, Germany. In all groups 0.3-100 Hz analog filtering, sampling rate 1000 Hz were used. Response speed and the accuracy of recognition error were used as parameters of behavioral reactions. Event-related potentials (ERP) responses P300 and P600 were used as indicators of brain activity. The accuracy of solving tasks and response speed in Russians were higher for Russian than for English. The P300 amplitudes in Russians were higher for English; the P600 amplitudes in the left temporal cortex were higher for the Russian language. Both Tuvinians and Yakuts have no difference in accuracy of solving tasks in Russian and in their respective national languages (Tuvinian and Yakut). However, the response speed was faster for tasks in Russian than for tasks in their national language. Tuvinians and Yakuts showed bad accuracy in English, but the response speed was higher for English than for Russian and the national languages. With Tuvinians, there were no differences in the P300 and P600 amplitudes and in cortical topology for Russian and Tuvinian, but there was a difference for English. In Yakuts, the P300 and P600 amplitudes and topology of ERP for Russian were the same as Russians had for Russian. In Yakuts, brain reactions during Yakut and English comprehension had no difference and were reflected foreign language comprehension -while the Russian language comprehension was reflected native language comprehension. We found out that the Tuvinians recognized both Russian and Tuvinian as native languages, and English as a foreign language. The Yakuts recognized both English and Yakut as a foreign language, only Russian as a native language. According to the inquirer, both Tuvinians and Yakuts use the national language as a spoken language, whereas they don’t use it for writing. It can well be a reason that Yakuts perceive the Yakut writing language as a foreign language while writing Russian as their native.

Keywords: EEG, language comprehension, native and foreign languages, Siberian inhabitants

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Authors: Ali Hamza

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Accurate segmentation of breast ultrasound images is of paramount importance in enhancing the diagnostic capabilities of breast cancer detection. This study presents an approach utilizing the U-Net architecture for segmenting breast ultrasound images aimed at improving the accuracy and reliability of mass identification within the breast tissue. The proposed method encompasses a multi-stage process. Initially, preprocessing techniques are employed to refine image quality and diminish noise interference. Subsequently, the U-Net architecture, a deep learning convolutional neural network (CNN), is employed for pixel-wise segmentation of regions of interest corresponding to potential breast masses. The U-Net's distinctive architecture, characterized by a contracting and expansive pathway, enables accurate boundary delineation and detailed feature extraction. To evaluate the effectiveness of the proposed approach, an extensive dataset of breast ultrasound images is employed, encompassing diverse cases. Quantitative performance metrics such as the Dice coefficient, Jaccard index, sensitivity, specificity, and Hausdorff distance are employed to comprehensively assess the segmentation accuracy. Comparative analyses against traditional segmentation methods showcase the superiority of the U-Net architecture in capturing intricate details and accurately segmenting breast masses. The outcomes of this study emphasize the potential of the U-Net-based segmentation approach in bolstering breast ultrasound image analysis. The method's ability to reliably pinpoint mass boundaries holds promise for aiding radiologists in precise diagnosis and treatment planning. However, further validation and integration within clinical workflows are necessary to ascertain their practical clinical utility and facilitate seamless adoption by healthcare professionals. In conclusion, leveraging the U-Net architecture for breast ultrasound image segmentation showcases a robust framework that can significantly enhance diagnostic accuracy and advance the field of breast cancer detection. This approach represents a pivotal step towards empowering medical professionals with a more potent tool for early and accurate breast cancer diagnosis.

Keywords: mage segmentation, U-Net, deep learning, breast cancer detection, diagnostic accuracy, mass identification, convolutional neural network

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Authors: M. Al Huwayz, A. Salhi, S. Alhassan, S. Alotaibi, A. Almalki, M.Almunyif, A. Alhassni, M. Henini

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Recently, there has been much research carried out to investigate quantum dots (QDs) lasers with the aim to increase the gain of quantum well lasers. However, one of the difficulties with these structures is that electrically active defects can lead to serious issues in the performance of these devices. It is therefore essential to fully understand the types of defects introduced during the growth and/or the fabrication process. In this study, the effects of Gamma radiation on the electrically active defects in p-i-n InAs/InGaAsQDs laser structures grown by Molecular Beam Epitaxy (MBE) technique on GaAs substrates were investigated. Deep Level Transient Spectroscopy (DLTS), current-voltage (I-V), and capacitance-voltage (C-V) measurements were performed to explore these effects on the electrical properties of these QDs lasers. I-V measurements showed that as-grown sample had better electrical properties than the irradiated sample. However, DLTS and Laplace DLTS measurements at different reverse biases revealed that the defects in the-region of the p-i-n structures were decreased in the irradiated sample. In both samples, a trap with an activation energy of ~ 0.21 eV was assigned to the well-known defect M1 in GaAs layers

Keywords: quantum dots laser structures, gamma radiation, DLTS, defects, nAs/IngaAs

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Authors: Zeinab Jafari A., Ali Sharifnezhad B., Mohammad Razi C., Mohammad Haghpanahi D., Arash Maghsoudi

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Background and Objective: Sports-related rupture of the anterior cruciate ligament (ACL) and following injuries have been associated with various disorders, such as long-lasting changes in muscle activation patterns in athletes, which might last after ACL reconstruction (ACLR). The rupture of the ACL might result in abnormal patterns of movement execution, extending the treatment period and delaying athletes’ return to sports (RTS). As ACL injury is especially prevalent among athletes, the lengthy treatment process and athletes’ absence from sports are of great concern to athletes and coaches. Thus, estimating safe time of RTS is of crucial importance. Therefore, using a deep neural network (DNN) to classify the health levels of ACL in injured athletes, this study aimed to estimate the safe time for athletes to return to competitions. Methods: Ten athletes with ACLR and fourteen healthy controls participated in this study. Three health levels of ACL were defined: healthy, six-month post-ACLR surgery and nine-month post-ACLR surgery. Athletes with ACLR were tested six and nine months after the ACLR surgery. During the course of this study, surface electromyography (sEMG) signals were recorded from five knee muscles, namely Rectus Femoris (RF), Vastus Lateralis (VL), Vastus Medialis (VM), Biceps Femoris (BF), Semitendinosus (ST), during single-leg drop landing (SLDL) and forward hopping (SLFH) tasks. The Pseudo-Wigner-Ville distribution (PWVD) was used to produce three-dimensional (3-D) images of the energy distribution patterns of sEMG signals. Then, these 3-D images were converted to two-dimensional (2-D) images implementing the heat mapping technique, which were then fed to a deep convolutional neural network (DCNN). Results: In this study, we estimated the safe time of RTS by designing a DCNN classifier with an accuracy of 90 %, which could classify ACL into three health levels. Discussion: The findings of this study demonstrate the potential of the DCNN classification technique using sEMG signals in estimating RTS time, which will assist in evaluating the recovery process of ACLR in athletes.

Keywords: anterior cruciate ligament reconstruction, return to sports, surface electromyography, deep convolutional neural network

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Authors: Seema Dhariwal, Kiran Maan, Ruchi Baghel, Apoorva Sharma, Poonam Rana

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Introduction: Traumatic brain injury (TBI) is defined as the temporary or permanent alteration in brain function and pathology caused by an external mechanical force. It represents the leading cause of mortality and morbidity among children and youth individuals. Various models of TBI in rodents have been developed in the laboratory to mimic the scenario of injury. Blast overpressure injury is common among civilians and military personnel, followed by accidents or explosive devices. In addition to this, the lateral Controlled cortical impact (CCI) model mimics the blunt, penetrating injury. Method: In the present study, we have developed two different mild TBI models using blast and CCI injury. In the blast model, helium gas was used to create an overpressure of 130 kPa (±5) via a shock tube, and CCI injury was induced with an impact depth of 1.5mm to create diffusive and focal injury, respectively. C57BL/6J male mice (10-12 weeks) were divided into three groups: (1) control, (2) Blast treated, (3) CCI treated, and were exposed to different injury models. Serum was collected on Day1 and day7, followed by biphasic extraction using MTBE/Methanol/Water. Prepared samples were separated on Charged Surface Hybrid (CSH) C18 column and acquired on UHPLC-Q-TOF-MS using ESI probe with inhouse optimized parameters and method. MS peak list was generated using Markerview TM. Data were normalized, Pareto-scaled, and log-transformed, followed by multivariate and univariate analysis in metaboanalyst. Result and discussion: Untargeted profiling of lipids generated extensive data features, which were annotated through LIPID MAPS® based on their m/z and were further confirmed based on their fragment pattern by LipidBlast. There is the final annotation of 269 features in the positive and 182 features in the negative mode of ionization. PCA and PLS-DA score plots showed clear segregation of injury groups to controls. Among various lipids in mild blast and CCI, five lipids (Glycerophospholipids {PC 30:2, PE O-33:3, PG 28:3;O3 and PS 36:1 } and fatty acyl { FA 21:3;O2}) were significantly altered in both injury groups at Day 1 and Day 7, and also had VIP score >1. Pathway analysis by Biopan has also shown hampered synthesis of Glycerolipids and Glycerophospholipiods, which coincides with earlier reports. It could be a direct result of alteration in the Acetylcholine signaling pathway in response to TBI. Understanding the role of a specific class of lipid metabolism, regulation and transport could be beneficial to TBI research since it could provide new targets and determine the best therapeutic intervention. This study demonstrates the potential lipid biomarkers which can be used for injury severity diagnosis and identification irrespective of injury type (diffusive or focal).

Keywords: LipidBlast, lipidomic biomarker, LIPID MAPS®, TBI

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Authors: Sushish Baral, Pratibha Joshi, Yaman Maharjan

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Glaucoma is a chronic eye condition that causes vision loss that is irreversible. Early detection and treatment are critical to prevent vision loss because it can be asymptomatic. For the identification of glaucoma, multiple deep learning algorithms are used. Transformer-based architectures, which use the self-attention mechanism to encode long-range dependencies and acquire extremely expressive representations, have recently become popular. Convolutional architectures, on the other hand, lack knowledge of long-range dependencies in the image due to their intrinsic inductive biases. The aforementioned statements inspire this thesis to look at transformer-based solutions and investigate the viability of adopting transformer-based network designs for glaucoma detection. Using retinal fundus images of the optic nerve head to develop a viable algorithm to assess the severity of glaucoma necessitates a large number of well-curated images. Initially, data is generated by augmenting ocular pictures. After that, the ocular images are pre-processed to make them ready for further processing. The system is trained using pre-processed images, and it classifies the input images as normal or glaucoma based on the features retrieved during training. The Vision Transformer (ViT) architecture is well suited to this situation, as it allows the self-attention mechanism to utilise structural modeling. Extensive experiments are run on the common dataset, and the results are thoroughly validated and visualized.

Keywords: glaucoma, vision transformer, convolutional architectures, retinal fundus images, self-attention, deep learning

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Authors: Jingting Luo, Yong Wang, Ying Wang

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Pedestrian detection in image or video data is a very important and challenging task in security surveillance. The difficulty of this task is to locate and detect pedestrians of different scales in complex scenes accurately. To solve these problems, a deep neural network (RT-YOLOv3) is proposed to realize real-time pedestrian detection at different scales in security monitoring. RT-YOLOv3 improves the traditional YOLOv3 algorithm. Firstly, the deep residual network is added to extract vehicle features. Then six convolutional neural networks with different scales are designed and fused with the corresponding scale feature maps in the residual network to form the final feature pyramid to perform pedestrian detection tasks. This method can better characterize pedestrians. In order to further improve the accuracy and generalization ability of the model, a hybrid pedestrian data set training method is used to extract pedestrian data from the VOC data set and train with the INRIA pedestrian data set. Experiments show that the proposed RT-YOLOv3 method achieves 93.57% accuracy of mAP (mean average precision) and 46.52f/s (number of frames per second). In terms of accuracy, RT-YOLOv3 performs better than Fast R-CNN, Faster R-CNN, YOLO, SSD, YOLOv2, and YOLOv3. This method reduces the missed detection rate and false detection rate, improves the positioning accuracy, and meets the requirements of real-time detection of pedestrian objects.

Keywords: pedestrian detection, feature detection, convolutional neural network, real-time detection, YOLOv3

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Authors: Faisal A. Salih

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Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

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Authors: M. G. Nasuruddin, S. Ishak

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In anthropological medicine (traditional therapeutic healing) symbolic interface are used to connect with the cognitive and metacognitive mechanisms to activate conscious and unconscious response of patients or other recipients. At the same time they are used to communicate with the inhabitants of the nether world to whom are ascribed almost all cases of psychosomatic illness. The symbols, which are cultural specific, are divided into verbal and non-verbal forms of communication. The verbal forms are chanting of mantra and doa and the invocation to invoke the spirits while the non-verbal ones are the physical materials such as the offerings, props and decorative elements, music, movements, olfactory sensation and the performance space. The process of communication through these symbols is affected by the Shaman who is a link or intermediary between the healer (Shaman) and the patients and between the healer and the spirits of the nether world. The paper also examines the scientific perspective of the traditional healing through the use of these symbols. The response to these symbols as external stimuli is embedded in the genes that are linked to the hereditary factor in the person’s DNA. When the patients are tuned in to external stimuli such as music, chanting and singing (sonic orders), it can triggers a response from the brain, which may activate its inner pharmacy by releasing drugs such as dopamine and/or opiodsto ameliorate pain and counter depression, anxiety and create a feel good feeling. These symbols act like placebo, evoking the power of the mind over the body and triggering the innate self-healing energy. At the same time they could also be used as nocebo, for example black magic, which has the opposite effect of placebo. In whatever capacity they operate these symbols, which are either visual or auditory, is an integral part of anthropological medicine. For they communicate and conjure emotional responses that are conducive to healing by activating the internal brain pharmacy.

Keywords: communication, healing, placebo, nacebo, symbol

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Authors: Tiffany Baetens, Sophie Halliez, Luc Buée, Emiliano Pallecchi, Vincent Thomy, Steve Arscott

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We demonstrate here a viable stretchable bio-microelectromechanical systems (BioMEMS) technology for use with biological studies concerned with the effect of high mechanical strains on living cells. An example of this is traumatic brain injury (TBI) where neurons are damaged with physical force to the brain during, e.g., accidents and sports. Robust, miniaturized integrated systems are needed by biologists to be able to study the effect of TBI on neuron cells in vitro. The major challenges in this area are (i) to develop micro, and nanofabrication processes which are based on stretchable substrates and to (ii) create systems which are robust and performant at very high mechanical strain values—sometimes as high as 100%. At the time of writing, such processes and systems were rapidly evolving subject of research and development. The BioMEMS which we present here is composed of an elastomer substrate (low Young’s modulus ~1 MPa) onto which is patterned robust electrodes and insulators. The patterning of the thin films is achieved using standard photolithography techniques directly on the elastomer substrate—thus making the process generic and applicable to many materials’ in based systems. The chosen elastomer used is commercial ‘Sylgard 184’ polydimethylsiloxane (PDMS). It is spin-coated onto a silicon wafer. Multistep ultra-violet based photolithography involving commercial photoresists are then used to pattern robust thin film metallic electrodes (chromium/gold) and insulating layers (parylene) on the top of the PDMS substrate. The thin film metals are deposited using thermal evaporation and shaped using lift-off techniques The BioMEMS has been characterized mechanically using an in-house strain-applicator tool. The system is composed of 12 electrodes with one reference electrode transversally-orientated to the uniaxial longitudinal straining of the system. The electrical resistance of the electrodes is observed to remain very stable with applied strain—with a resistivity approaching that of evaporated gold—up to an interline strain of ~50%. The mechanical characterization revealed some interesting original properties of such stretchable BioMEMS. For example, a Poisson effect induced electrical ‘self-healing’ of cracking was identified. Biocompatibility of the commercial photoresist has been studied and is conclusive. We will present the results of the BioMEMS, which has also characterized living cells with a commercial Multi Electrode Array (MEA) characterization tool (Multi Channel Systems, USA). The BioMEMS enables the cells to be strained up to 50% and then characterized electrically and optically.

Keywords: BioMEMS, elastomer, electrical impedance measurements of living cells, high mechanical strain, microfabrication, stretchable systems, thin films, traumatic brain injury

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Authors: Elizabeta Eduard Baltadzhyan

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This work presents a stage of an investigation about the metaphorical conceptualization of translation in Bulgarian language. The material is a linguistic corpus consisting of 38 interviews with several generations Bulgarian translators and interpreters. The aim of this presentation is to inform about the results of the organization of the source concepts in scenarios that dominate the discursive manifestations of the source domains. The data show that, on the one hand, translators from different generations share some basic assignments of source and target domains, e. g. translation is a journey or translation is an artistic presentation. On the other hand, there are some specific scenarios motivated by significant changes in the socio-economic structure of the country and the valuation of the translator´s mission and work, e. g., the scenario of pleasure and addictive activity marks the generation that enjoy great support and stimulation from the socialist government, whereas the war scenario marks the generation during the Perestroika time.

Keywords: Bulgarian language, metaphor, scenario, translation

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Authors: Jean-Francois Rajotte, Martin Sotir, Frank Gouineau

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The installation and management of traffic monitoring devices can be costly from both a financial and resource point of view. It is therefore important to take advantage of in-place infrastructures to extract the most information. Here we show how low-quality urban road traffic images from cameras already available in many cities (such as Montreal, Vancouver, and Toronto) can be used to estimate traffic flow. To this end, we use a pre-trained neural network, developed for object detection, to count vehicles within images. We then compare the results with human annotations gathered through crowdsourcing campaigns. We use this comparison to assess performance and calibrate the neural network annotations. As a use case, we consider six months of continuous monitoring over hundreds of cameras installed in the city of Montreal. We compare the results with city-provided manual traffic counting performed in similar conditions at the same location. The good performance of our system allows us to consider applications which can monitor the traffic conditions in near real-time, making the counting usable for traffic-related services. Furthermore, the resulting annotations pave the way for building a historical vehicle counting dataset to be used for analysing the impact of road traffic on many city-related issues, such as urban planning, security, and pollution.

Keywords: traffic monitoring, deep learning, image annotation, vehicles, roads, artificial intelligence, real-time systems

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Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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Authors: Bashar Tarawneh, Yasser Hakam

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Rapid Impact Compaction (RIC) is a modern dynamic compaction device mainly used to compact sandy soils, where silt and clay contents are low. The device uses the piling hammer technology to increase the bearing capacity of soils through controlled impacts. The RIC device uses "controlled impact compaction" of the ground using a 9-ton hammer dropped from the height between 0.3 m to 1.2 m onto a 1.5 m diameter steel patent foot. The delivered energy is about 26,487 to 105,948 Joules per drop. To evaluate the performance of this technique, three project sites in the United Arab Emirates were improved using RIC. In those sites, a loose to very loose fine to medium sand was encountered at a depth ranging from 1.0m to 4.0m below the ground level. To evaluate the performance of the RIC, Cone Penetration Tests (CPT) were carried out before and after improvement. Also, load tests were carried out post-RIC work to assess the settlements and bearing capacity. The soil was improved to a depth of about 5.0m below the ground level depending on the CPT friction ratio (the ratio between sleeve friction and tip resistance). CPT tip resistance was significantly increased post ground improvement work. Load tests showed enhancement in the soil bearing capacity and reduction in the potential settlements. This study demonstrates the successful application of the RIC for middle-deep improvement and compaction of the ground. Foundation design criteria were achieved in all site post-RIC work.

Keywords: compaction, RIC, ground improvement, CPT

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Authors: Zahra Fotovatnia, Jeffery A. Jones, Alexandra Gottardo

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Speech communication often occurs in environments where noise conceals part of a message. Listeners should compensate for the lack of auditory information by picking up distinct acoustic cues and using semantic and sentential context to recreate the speaker’s intended message. This situation seems to be more challenging in a nonnative than native language. On the other hand, early bilinguals are expected to show an advantage over the late bilingual and monolingual speakers of a language due to their better executive functioning components. In this study, English monolingual speakers were compared with early and late nonnative speakers of English to understand speech in noise processing (SIN) and the underlying neurobiological features of this phenomenon. Auditory mismatch negativities (MMNs) were recorded using a double-oddball paradigm in response to a minimal pair that differed in their middle vowel (beat/bit) at Wilfrid Laurier University in Ontario, Canada. The results did not show any significant structural and electroneural differences across groups. However, vocabulary knowledge correlated positively with performance on tests that measured SIN processing in participants who learned English after age 6. Moreover, their performance on the test negatively correlated with the integral area amplitudes in the left superior temporal gyrus (STG). In addition, the STG was engaged before the inferior frontal gyrus (IFG) in noise-free and low-noise test conditions in all groups. We infer that the pre-attentive processing of words engages temporal lobes earlier than the fronto-central areas and that vocabulary knowledge helps the nonnative perception of degraded speech.

Keywords: degraded speech perception, event-related brain potentials, mismatch negativities, brain regions

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Authors: Lin Li, Farshad Amini

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The flipped classroom has been introduced to promote collaborative learning and higher-order learning objectives. In contrast to the traditional classroom, the flipped classroom has students watch prerecorded lecture videos before coming to class and then “class becomes the place to work through problems, advance concepts, and engage in collaborative learning”. In this paper, the active flipped learning combines flipped classroom with active learning that is to establish an active flipped learning (AFL) model, aiming to promote active learning, stress deep learning, encourage student engagement and highlight data-driven personalized learning. Because students have watched the lecture prior to class, contact hours can be devoted to problem-solving and gain a deeper understanding of the subject matter. The instructor is able to provide students with a wide range of learner-centered opportunities in class for greater mentoring and collaboration, increasing the possibility to engage students. Currently, little is known about the extent to which AFL improves engineering students’ performance. This paper presents the preliminary study on the core course of sophomore students in Engineering Mechanics. A series of survey and interviews have been conducted to compare students’ learning engagement, empowerment, self-efficacy, and satisfaction with the AFL. It was found that the AFL model taking advantage of advanced technology is a convenient and professional avenue for engineering students to strengthen their academic confidence and self-efficacy in the Engineering Mechanics by actively participating in learning and fostering their deep understanding of engineering statics and dynamics

Keywords: active learning, engineering mechanics, flipped classroom, performance

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Authors: Cathal Merz, Gareth O’Donnell

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Coil reinforced thin-walled (CRTW) tubes are used in medicine to treat problems affecting blood vessels within the body through minimally invasive procedures. The CRTW tube considered in this research makes up part of such a device and is inserted into the patient via their femoral or brachial arteries and manually navigated to the site in need of treatment. This procedure replaces the requirement to perform open surgery but is limited by reduction of blood vessel lumen diameter and increase in tortuosity of blood vessels deep in the brain. In order to maximize the capability of these procedures, CRTW tube devices are being manufactured with decreasing wall thicknesses in order to deliver treatment deeper into the body and to allow passage of other devices through its inner diameter. This introduces significant stresses to the device materials which have resulted in an observed increase in the breaking of the proximal segment of the device into two separate pieces after it has failed by buckling. As there is currently no international standard for measuring the mechanical properties of these CRTW tube devices, it is difficult to accurately analyze this problem. The aim of the current work is to address this discrepancy in the biomedical device industry by developing a measurement system that can be used to quantify the effect of process and design changes on CRTW tube performance, aiding in the development of better performing, next generation devices. Using materials testing frames, micro-computed tomography (micro-CT) imaging, experiment planning, analysis of variance (ANOVA), T-tests and regression analysis, test methods have been developed for assessing the impact of process and design changes on the device. The major findings of this study have been an insight into the suitability of buckle and three-point bend tests for the measurement of the effect of varying processing factors on the device’s performance, and guidelines for interpreting the output data from the test methods. The findings of this study are of significant interest with respect to verifying and validating key process and design changes associated with the device structure and material condition. Test method integrity evaluation is explored throughout.

Keywords: neurovascular catheter, coil reinforced tube, buckling, three-point bend, tensile

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Authors: Caroline Lavratti, Pedro Dal Lago, Gustavo Reinaldo, Gilson Dorneles, Andreia Bard, Laira Fuhr, Daniela Pochmann, Alessandra Peres, Luciane Wagner, Viviane Elsner

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Approximately 1% of the world's population is affected by schizophrenia (SZ), a chronic and debilitating neurodevelopmental disorder. Among possible factors, reduced levels of Brain-derived neurotrophic factor (BDNF) has been recognized in physiopathogenesis and course of SZ. In this context, peripheral BDNF levels have been used as a biomarker in several clinical studies, since this neurotrophin is able to cross the blood-brain barrier in a bi-directional manner and seems to present a strong correlation with the central nervous system fluid levels. The patients with SZ usually adopts a sedentary lifestyle, which has been partly associated with the increase in obesity incidence rates, metabolic syndrome, type 2 diabetes and coronary heart disease. On the other hand, exercise, a non-invasive and low cost intervention, has been considered an important additional therapeutic option for this population, promoting benefits to physical and mental health. To our knowledge, few studies have been pointed out that the positive effects of exercise in SZ patients are mediated, at least in part, to enhanced levels of BDNF after training. However, these studies are focused on evaluating the effect of single bouts of exercise of chronic interventions, data concerning the short- and long-term exercise outcomes on BDNF are scarce. Therefore, this study aimed to evaluate the effect of a concurrent exercise protocol (CEP) on plasma BDNF levels of SZ patients in different time-points. Material and Methods: This study was approved by the Research Ethics Committee of the Centro Universitário Metodista do IPA (no 1.243.680/2015). The participants (n=15) were subbmited to the CEP during 90 days, 3 times a week for 60 minutes each session. In order to evaluate the short and long-term effects of exercise, blood samples were collected pre, 30, 60 and 90 days after the intervention began. Plasma BDNF levels were determined with the ELISA method, from Sigma-Aldrich commercial kit (catalog number RAB0026) according to manufacturer's instructions. Results: A remarkable increase on plasma BDNF levels at 90 days after training compared to baseline (p=0.006) and 30 days (p=0.007) values were observed. Conclusion: Our data are in agreement with several studies that show significant enhancement on BDNF levels in response to different exercise protocols in SZ individuals. We might suggest that BDNF upregulation after training in SZ patients acts in a dose-dependent manner, being more pronounced in response to chronic exposure. Acknowledgments: This work was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)/Brazil.

Keywords: exercise, BDNF, schizophrenia, time-points

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Authors: Mahsa Hadipour Jahromy, Sara Rezaii

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Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Soon after the discovery of levodopa and its beneficial effects in chronic administration, debilitating involuntary movements observed, termed levodopa-induced dyskinesia (LID) with poorly understood pathogenesis. Polyphenol-rich compounds, like pomegranate, provided neuroprotection in several animal models of brain diseases. In the present work, we investigated whether pomegranate has preventive effects following 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degenerations and the potential to diminish LID in mice. Mice model of PD was induced by MPTP (30 mg/kg daily for five consecutive days). To induce a mice model of LID, valid PD mice were treated with levodopa (50 mg/kg, i.p) for 15 days. Then the effects of chronic co-administration of pomegranate juice (20 ml/kg) with levodopa and continuing for 10 days, evaluated. Behavioural tests were performed in all groups, every other day including: Abnormal involuntary movements (AIMS), forelimb adjusting steps, cylinder, and catatonia tests. Finally, brain tissue sections were prepared to study substantia nigra changes and dopamine neuron density after treatments. With this MPTP regimen, significant movement disorders revealed in AIMS tests and there was a reduction in dopamine striatal density. Levodopa attenuates their loss caused by MPTP, however, in chronic administration, dyskinesia observed in forelimb adjusting step and cylinder tests. Besides, catatonia observed in some cases. Chronic pomegranate co-administration significantly improved LID in both tests and reduced dopaminergic loss in substantia nigra. These data indicate that pomegranate might be a good adjunct for preserving dopaminergic neurons in the substantia nigra and reducing LID in mice.

Keywords: levodopa-induced dyskinesia, MPTP, Parkinson’s disease, pomegranate

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Authors: Kishore Kumar R., Kaustav Sengupta, Shalini Sood Sehgal, Poornima Santhanam

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Fashion is a human expression that is constantly changing. One of the prime factors that consistently influences fashion is the change in colour preferences. The role of colour in our everyday lives is very significant. It subconsciously explains a lot about one’s mindset and mood. Analyzing the colours by extracting them from the outfit images is a critical study to examine the individual’s/consumer behaviour. Several research works have been carried out on extracting colours from images, but to the best of our knowledge, there were no studies that extract colours to specific apparel and identify colour patterns geographically. This paper proposes a framework for accurately extracting colours from T-shirt images and predicting dominant colours geographically. The proposed method consists of two stages: first, a U-Net deep learning model is adopted to segment the T-shirts from the images. Second, the colours are extracted only from the T-shirt segments. The proposed method employs the iMaterialist (Fashion) 2019 dataset for the semantic segmentation task. The proposed framework also includes a mechanism for gathering data and analyzing India’s general colour preferences. From this research, it was observed that black and grey are the dominant colour in different regions of India. The proposed method can be adapted to study fashion’s evolving colour preferences.

Keywords: colour analysis in t-shirts, convolutional neural network, encoder-decoder, k-means clustering, semantic segmentation, U-Net model

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Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Javaid Irfan, Andreas G. Schätzlein, Ijeoma F Uchegbeu

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Development of efficient delivery system for hydrophobic drugs remains a major concern in chemotherapy. The objective of the current study was to develop polymeric drug-delivery system for etoposide from amphiphilic derivatives of glycol chitosan, capable to improve the pharmacokinetics and to reduce the adverse effects of etoposide due to various organic solvents used in commercial formulations for solubilisation of etoposide. As a promising carrier, amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxy succinimide and quaternisation to glycol chitosan backbone. To this end a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternisation into 13 kDa. Nano sized micelles prepared from this amphiphilic polymer had the capability to encapsulate up to 3 mg/ml etoposide. The pharmacokinetic results indicated that GCPQ based etoposide formulation transformed the biodistribution pattern. AUC 0.5-24 hr showed statistically significant difference in ETP-GCPQ vs. commercial preparation in liver (25 vs 70, p<0.001), spleen (27 vs. 36, P<0.05), lungs (42 vs. 136, p<0.001), kidneys (25 vs. 30, p<0.05) and brain (19 vs. 9,p<0.001). Using the hydrophobic fluorescent dye Nile red, we showed that micelles efficiently delivered their payload to MCF7 and A2780 cancer cells in-vitro and to A431 xenograft tumor in-vivo, suggesting these systems could deliver hydrophobic anti- cancer drugs such as etoposide to tumors. The pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drug after intravenous administration. GCPQ based formulations not only reduced side effects associated with current available formulations but also increased their transport through the biological barriers, thus making it a good delivery system.

Keywords: glycol chitosan, Nile red, micelles, etoposide, A431 xenografts

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