Search results for: brain tumor segmentation

Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Tuiana A. Aiusheeva, Sergey S. Tamozhnikov, Alexander E. Saprygin, Arina A. Antonenko, Valentina V. Stepanova, Natalia N. Tolstykh, Alexander N. Savostyanov

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Situation of choice is an important condition for the formation of essential character qualities of a child, such as being initiative, responsible, hard-working. We have studied the behavioral and EEG reactions in Russian schoolchildren during recognition of syntactic errors in emotionally colored sentences that describe the choice situation. Twenty healthy children (mean age 9,0±0,3 years, 12 boys, 8 girls) were examined. Forty sentences were selected for the experiment; the half of them contained a syntactic error. The experiment additionally had the hidden condition: 50% of the sentences described the children's own choice and were emotionally colored (positive or negative). The other 50% of the sentences described the forced-choice situation, also with positive or negative coloring. EEG were recorded during execution of error-recognition task. Reaction time and quality of syntactic error detection were chosen as behavioral measures. Event-related spectral perturbation (ERSP) was applied to characterize the oscillatory brain activity of children. There were two time-frequency intervals in EEG reactions: (1) 500-800 ms in the 3-7 Hz frequency range (theta synchronization) and (2) 500-1000 ms in the 8-12 Hz range (alpha desynchronization). We found out that behavioral and brain reactions in child brain during recognition of positive and negative sentences describing forced-choice situation did not have significant differences. Theta synchronization and alpha desynchronization were stronger during recognition of sentences with children's own choice, especially with negative coloring. Also, the quality and execution time of the task were higher for this types of sentences. The results of our study will be useful for improvement of teaching methods and diagnostics of children affective disorders.

Keywords: choice situation, electroencephalogram (EEG), emotionally colored sentences, schoolchildren

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Authors: M. Safiqul Islam, Md Arafat Hossain Sarkar

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Brachytherapy is one of the most important cancer treatment management systems in radiotherapy department. Brachytherapy treatment is moved into High Dose Rate (HDR) after loader from Low Dose Rate (LDR) after loader due to radiation protection advantage. HDR Brachytherapy is a highly multipurpose system for enhancing cure and achieving palliation in many common cancers disease of developing countries. High-dose rate (HDR) Brachytherapy is a type of internal radiation therapy that delivers radiation from implants placed close to or inside, the tumor(s) in the body. This procedure is very effective at providing localized radiation to the tumor site while minimizing the patient’s whole body dose. Brachytherapy has proven to be a highly successful treatment for cancers of the prostate, cervix, endometrium, breast, skin, bronchus, esophagus, and head and neck, as well as soft tissue sarcomas and several other types of cancer. For the time being in our country we have 10 new HDR Remote after loading Brachytherapy. Right now 4 HDR Brachytherapy is already installed and running for patient’s treatment out of 10 HDR Brachytherapy. Ir-192 source is more comfortable than Co-60. In that case people or expert personnel prefer Ir-192 source for different kind of cancer patients. Ir-192 are economically, more flexible and familiar in our country.

Keywords: Ir-192, brachytherapy, cancer treatment, prostate, cervix, endometrium, breast, skin, bronchus, esophagus, soft tissue sarcomas

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Authors: Aml M. El-Sharkawy, Hossam M. Darwesh

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Abstract— Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between tumor associated trypsin inhibitor (TATI) and HCC progression, we aimed to develop a novel score based on combination of TATI and routine laboratory tests for early prediction of HCC. Methods: TATI was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-TATI score) = 3.1 (numerical constant) + 0.09 ×AFP (U L-1) + 0.067 × TATI (ng ml-1) + 0.16 × INR – 1.17 × Albumin (g l-1) – 0.032 × Platelet count × 109 l-1 was developed. HCC-TATI score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 6.5 (ie less than 6.5 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-TATI score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, TATI

Procedia PDF Downloads 332

Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

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In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

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Authors: Muktadir Ahmed, Sayed Akhlakur Rahaman, Mridha Shihab Mahmud

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The parents of Bangladesh have scarcity of knowledge about children play. Most of them do not know which toys are perfect for their children. Appropriate toys for playing is one of the most significant parts of children development from early age, besides for proper amelioration of children’s mental growth and brain capacities, toys play an emergent role. So selection of proper toy for children is very important. A toy forms the sagacity of a child and instructs child’s attitude. In this era of globalization to keep pace with everything children toys are also going forward but in a deleterious way. Maximum toys are now battery-driven and for this psychological developments of children are not increasing in effective way; therefore, pedagogical toys are proper selection. This type of toy inspires the wisdom and helps a child to reveal himself/herself. Pedagogical toys are attractive to children and help to stimulate their imagination. Pedagogical toys help them to build senso-motoric skills and hand-eye coordination. In this study, some children divided into two groups, one group played with pedagogical toys and another group played with conventional toys. This study is going to exhibit the difference between pedagogical and conventional toys for kids. The main aim of this study is to reveal the potency of pedagogical toy for children. To implement this study two Daycare Centers (DCC) Projapoti 1 & 3 of Mymensingh city had chosen. Every DCC having 1.5-6 years old children but for this study 2-5 years old children had been selected. The children of Projapoti-1 played with pedagogical toys and the children of Projapoti-2 played with conventional toys. After 6 weeks of study, the children of Projapoti-1 proved that they have improved their skills more than those children of Projapoti-3 who were playing with conventional toys. The children of Projapoti-1 have developed their touch sensation, muscular movement, imitation power, hand-eye coordination whereas the children of Projapoti-3 have only developed their muscular movement fairly (while running after battery driven toys) which is not better than those children of Projapoti-1. They cannot imitate like the children of Projapoti-1. They just had fun from playing virtual games, battery driven toys, watching cartoons etc. Actually, it is not possible to develop a child’s brain without pedagogical toy.

Keywords: brain development, mental growth, pedagogical toys, play for children

Procedia PDF Downloads 322

Authors: Marc Sebastián-Romagosa, Woosang Cho, Rupert Ortner, Christy Li, Christoph Guger

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Neurorehabilitation based on Brain-Computer Interfaces (BCIs) shows important rehabilitation effects for patients after stroke. Previous studies have shown improvements for patients that are in a chronic stage and/or have severe hemiparesis and are particularly challenging for conventional rehabilitation techniques. For this publication, seven stroke patients in the chronic phase with hemiparesis in the lower extremity were recruited. All of them participated in 25 BCI sessions about 3 times a week. The BCI system was based on the Motor Imagery (MI) of the paretic ankle dorsiflexion and healthy wrist dorsiflexion with Functional Electrical Stimulation (FES) and avatar feedback. Assessments were conducted to assess the changes in motor improvement before, after and during the rehabilitation training. Our primary measures used for the assessment were the 10-meters walking test (10MWT), Range of Motion (ROM) of the ankle dorsiflexion and Timed Up and Go (TUG). Results show a significant increase in the gait speed in the primary measure 10MWT fast velocity of 0.18 m/s IQR = [0.12 to 0.2], P = 0.016. The speed in the TUG was also significantly increased by 0.1 m/s IQR = [0.09 to 0.11], P = 0.031. The active ROM assessment increased 4.65º, and IQR = [ 1.67 - 7.4], after rehabilitation training, P = 0.029. These functional improvements persisted at least one month after the end of the therapy. These outcomes show the feasibility of this BCI approach for chronic stroke patients and further support the growing consensus that these types of tools might develop into a new paradigm for rehabilitation tools for stroke patients. However, the results are from only seven chronic stroke patients, so the authors believe that this approach should be further validated in broader randomized controlled studies involving more patients. MI and FES-based non-invasive BCIs are showing improvement in the gait rehabilitation of patients in the chronic stage after stroke. This could have an impact on the rehabilitation techniques used for these patients, especially when they are severely impaired and their mobility is limited.

Keywords: neuroscience, brain computer interfaces, rehabilitat, stroke

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Authors: S. M. Abdullah Al Mamun

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Human Computer Interaction (HCI) is an excellent area for the researchers to make daily life more simple and fast. Necessary hardware equipments for any BCI are generally expensive and not affordable for most of the people. Emotiv is one of the solutions for this problem, which can provide electroencephalograph (EEG) signal and explain the brain activities. BCI virtual speller was one of the important applications for the people who have lost their hand or speaking ability because of diseases or unexpected accident. In this paper, a matrix speller has been designed for the first time for Bengali speaking people around the world. Bengali is one of the most commonly spoken languages. Among them, a lot of disabled person will be able to express their desire in their mother tongue. This application is also usable for the social networks and daily life communications. For this virtual keyboard, the well-known matrix speller method with column flashing is applied and controlled by single Emokey only. Emokey is a great feature which translates emotional state for application inputs. In this paper, it is presented that the ITR (Information Transfer Rate) were 29.4 bits/min and typing speed achieved up to 7.43 char/per min.

Keywords: brain computer interface, Emotiv EPOC, EEG, virtual keyboard, matrix speller

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Authors: Yousry El-Sayed Elbolkiny, Mohamed Labib Salem

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Background: Rosemary (ROLE) and costus (SLRE) have been established to show antioxidant effects. Aim: This study aimed to evaluate the ameliorating effects of ROLE and SLRE on the side effects induced by cisplatin (CIS) in tumor-bearing mice. Materials and Methods: Extracts of ROLE and SLRE were examined for their phytochemical activities. To evaluate their anti-tumor effects, mice were inoculated intraperitoneally (i.p.) with 2.5x105 Ehrlich ascites carcinoma (EAC) and then treated i.p. with CIS at days 3-7 and with ROLE (dose) or SLRE (dose) at days 3-14. Mice were sacrificed on day 14 for CBC and T-cell analyses. Results: Phytochemical analysis revealed that both ROLE and SLRE showed similar antioxidant activities. Treatment of EAC-bearing mice with CIS-induced antitumor efficacy of about 90%. Treatment with CIS in combination with ROLE or SLRE did not further enhance the antitumor activity of CIS. However, co-administration of ROLE or SLRE with CIS significantly increased the antitumor efficacy of CIS. Flow cytometric analysis showed that the numbers of CD4+ and CD8+ T cells were decreased in EAC-bearing mice after treatment with CIS. Treatment with both ROLE and SLRE improved the number of these cells. Conclusion: Combinatorial treatment with rosemary and costus can enhance the antitumor activity of CIS

Keywords: CBC, cisplantin, costus, rosemary

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Authors: Rami Hashish, Manon Limousis-Gayda, Caitlin H. McCleery

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Introduction: A leading cause of emergency room visits among youth (in the United States), is sports-related traumatic brain injuries. Mild traumatic brain injuries (mTBIs), also called concussions, are caused by linear and/or angular acceleration experienced at the head and represent an increasing societal burden. Due to the developing nature of the brain in youth, there is a great risk for long-term neuropsychological deficiencies following a concussion. Accordingly, the purpose of this paper is to investigate incidence rates of concussion across gender for the five most common youth sports in the United States. These include basketball, track and field, soccer, baseball (boys), softball (girls), football (boys), and volleyball (girls). Methods: A PubMed search was performed for four search themes combined. The first theme identified the outcomes (concussion, brain injuries, mild traumatic brain injury, etc.). The second theme identified the sport (American football, soccer, basketball, softball, volleyball, track, and field, etc.). The third theme identified the population (adolescence, children, youth, boys, girls). The last theme identified the study design (prevalence, frequency, incidence, prospective). Ultimately, 473 studies were surveyed, with 15 fulfilling the criteria: prospective study presenting original data and incidence of concussion in the relevant youth sport. The following data were extracted from the selected studies: population age, total study population, total athletic exposures (AE) and incidence rate per 1000 athletic exposures (IR/1000). Two One-Way ANOVA and a Tukey’s post hoc test were conducted using SPSS. Results: From the 15 selected studies, statistical analysis revealed the incidence of concussion per 1000 AEs across the considered sports ranged from 0.014 (girl’s track and field) to 0.780 (boy’s football). Average IR/1000 across all sports was 0.483 and 0.268 for boys and girls, respectively; this difference in IR was found to be statistically significant (p=0.013). Tukey’s post hoc test showed that football had significantly higher IR/1000 than boys’ basketball (p=0.022), soccer (p=0.033) and track and field (p=0.026). No statistical difference was found for concussion incidence between girls’ sports. Removal of football was found to lower the IR/1000 for boys without a statistical difference (p=0.101) compared to girls. Discussion: Football was the only sport showing a statistically significant difference in concussion incidence rate relative to other sports (within gender). Males were overall more likely to be concussed than females when football was included (1.8x), whereas concussion was more likely for females when football was excluded. While the significantly higher rate of concussion in football is not surprising because of the nature and rules of the sport, it is concerning that research has shown higher incidence of concussion in practices than games. Interestingly, findings indicate that girls’ sports are more concussive overall when football is removed. This appears to counter the common notion that boys’ sports are more physically taxing and dangerous. Future research should focus on understanding the concussive mechanisms of injury in each sport to enable effective rule changes.

Keywords: gender, football, soccer, traumatic brain injury

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Authors: Bechir Hbibi, Lamine Mili

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Understanding the condition of comatose patients can be difficult, but it is crucial to their optimal treatment. Consequently, numerous scoring systems have been developed around the world to categorize patient states based on physiological assessments. Although validated and widely adopted by medical communities, these scores still present numerous limitations and obstacles. Even with the addition of additional tests and extensions, these scoring systems have not been able to overcome certain limitations, and it appears unlikely that they will be able to do so in the future. On the other hand, physiological tests are not the only way to extract ideas about comatose patients. EEG signal analysis has helped extensively to understand the human brain and human consciousness and has been used by researchers in the classification of different levels of disease. The use of EEG in the ICU has become an urgent matter in several cases and has been recommended by medical organizations. In this field, the EEG is used to investigate epilepsy, dementia, brain injuries, and many other neurological disorders. It has recently also been used to detect pain activity in some regions of the brain, for the detection of stress levels, and to evaluate sleep quality. In our recent findings, our aim was to use multifractal analysis, a very successful method of handling multifractal signals and feature extraction, to establish a state of awareness scale for comatose patients based on their electrical brain activity. The results show that this score could be instantaneous and could overcome many limitations with which the physiological scales stock. On the contrary, multifractal analysis stands out as a highly effective tool for characterizing non-stationary and self-similar signals. It demonstrates strong performance in extracting the properties of fractal and multifractal data, including signals and images. As such, we leverage this method, along with other features derived from EEG signal recordings from comatose patients, to develop a scale. This scale aims to accurately depict the vigilance state of patients in intensive care units and to address many of the limitations inherent in physiological scales such as the Glasgow Coma Scale (GCS) and the FOUR score. The results of applying version V0 of this approach to 30 patients with known GCS showed that the EEG-based score similarly describes the states of vigilance but distinguishes between the states of 8 sedated patients where the GCS could not be applied. Therefore, our approach could show promising results with patients with disabilities, injected with painkillers, and other categories where physiological scores could not be applied.

Keywords: coma, vigilance state, EEG, multifractal analysis, feature extraction

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Authors: Rami Hashish, Manon Limousis-Gayda, Caitlin McCleery

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Introduction: Mild traumatic brain injuries, also referred to as concussions, represent an increasing burden to society. Due to limited objective diagnostic measures, concussions are diagnosed by assessing subjective symptoms, often leading to disputes to their presence. Common biomechanical measures associated with concussion are high linear and/or angular acceleration to the head. With regards to linear acceleration, approximately 80g’s has previously been shown to equate with a 50% probability of concussion. Motor vehicle collisions (MVCs) are a leading cause of concussion, due to high head accelerations experienced. The change in velocity (delta-V) of a vehicle in an MVC is an established metric for impact severity. As acceleration is the rate of delta-V with respect to time, the purpose of this paper is to determine the relation between delta-V (and occupant parameters) with linear head acceleration. Methods: A meta-analysis was conducted for manuscripts collected using the following keywords: head acceleration, concussion, brain injury, head kinematics, delta-V, change in velocity, motor vehicle collision, and rear-end. Ultimately, 280 studies were surveyed, 14 of which fulfilled the inclusion criteria as studies investigating the human response to impacts, reporting head acceleration, and delta-V of the occupant’s vehicle. Statistical analysis was conducted with SPSS and R. The best fit line analysis allowed for an initial understanding of the relation between head acceleration and delta-V. To further investigate the effect of occupant parameters on head acceleration, a quadratic model and a full linear mixed model was developed. Results: From the 14 selected studies, 139 crashes were analyzed with head accelerations and delta-V values ranging from 0.6 to 17.2g and 1.3 to 11.1 km/h, respectively. Initial analysis indicated that the best line of fit (Model 1) was defined as Head Acceleration = 0.465

Keywords: acceleration, brain injury, change in velocity, Delta-V, TBI

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Authors: Prajakta Patil, Yash Huzurbazar, Abhijeet Shinde

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Aim: To develop a treatment protocol for the management of tinnitus through multi-modality brain stimulation. Methodology: Present study included 33 adults with unilateral (31 subjects) and bilateral (2 subjects) chronic tinnitus with and/or without hearing loss independent of their etiology. The Treatment protocol included 5 consecutive sessions with follow-up of 6 months. Each session was divided into 3 parts: • Pre-treatment: a) Informed consent b) Pitch and loudness matching. • Treatment: Bimanual paper pen task with tinnitus masking for 30 minutes. • Post-treatment: a) Pitch and loudness matching b) Directive counseling and obtaining feedback. Paper-pen task is to be performed bimanually that included carrying out two different writing activities in different context. The level of difficulty of the activities was increased in successive sessions. Narrowband noise of a frequency same as that of tinnitus was presented at 10 dBSL of tinnitus for 30 minutes simultaneously in the ear with tinnitus. Result: The perception of tinnitus was no longer present in 4 subjects while in remaining subjects it reduced to an intensity that its perception no longer troubled them without causing residual facilitation. In all subjects, the intensity of tinnitus decreased by an extent of 45 dB at an average. However, in few subjects, the intensity of tinnitus also decreased by more than 45 dB. The approach resulted in statistically significant reductions in Tinnitus Functional Index and Tinnitus Handicap Inventory scores. The results correlate with pre and post treatment score of Tinnitus Handicap Inventory that dropped from 90% to 0%. Discussion: Brain mapping(qEEG) Studies report that there is multiple parallel overlapping of neural subnetworks in the non-auditory areas of the brain which exhibits abnormal, constant and spontaneous neural activity involved in the perception of tinnitus with each subnetwork and area reflecting a specific aspect of tinnitus percept. The paper pen task and directive counseling are designed and delivered respectively in a way that is assumed to induce normal, rhythmically constant and premeditated neural activity and mask the abnormal, constant and spontaneous neural activity in the above-mentioned subnetworks and the specific non-auditory area. Counseling was focused on breaking the vicious cycle causing and maintaining the presence of tinnitus. Diverting auditory attention alone is insufficient to reduce the perception of tinnitus. Conscious awareness of tinnitus can be suppressed when individuals engage in cognitively demanding tasks of non-auditory nature as the paper pen task used in the present study. To carry out this task selective, divided, sustained, simultaneous and split attention act cumulatively. Bimanual paper pen task represents a top-down activity which underlies brain’s ability to selectively attend to the bimanual written activity as a relevant stimulus and to ignore tinnitus that is the irrelevant stimuli in the present study. Conclusion: The study suggests that this novel treatment approach is cost effective, time saving and efficient to vanish the tinnitus or to reduce the intensity of tinnitus to a negligible level and thereby eliminating the negative reactions towards tinnitus.

Keywords: multi-modality brain stimulation, neural subnetworks, non-auditory areas, paper-pen task, top-down activity

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Authors: Mekdes Getu Chekol, Biniam Tedros Kahsay, Rahwa Berihu Haile

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The main objective of this study is to investigate the marketing strategy practice in the Case of St. George Brewery Factory in Addis Ababa. One of the core activities in a Business Company to stay in business is having a well-developed marketing strategy. It assessed how the marketing strategies were practiced in the company to achieve its goals aligned with segmentation, target market, positioning, and the marketing mix elements to satisfy customer requirements. Using primary and secondary data, the study is conducted by using both qualitative and quantitative approaches. The primary data was collected through open and closed-ended questionnaires. Considering the size of the population is small, the selection of the respondents was carried out by using a census. The finding shows that the company used all the 4 Ps of the marketing mix elements in its marketing strategies and provided quality products at affordable prices by promoting its products by using high and effective advertising mechanisms. The product availability and accessibility are admirable with the practices of both direct and indirect distribution channels. On the other hand, the company has identified its target customers, and the company’s market segmentation practice is geographical location. Communication effectiveness between the marketing department and other departments is very good. The adjusted R2 model explains 61.6% of the marketing strategy practice variance by product, price, promotion, and place. The remaining 38.4% of variation in the dependent variable was explained by other factors not included in this study. The result reveals that all four independent variables, product, price, promotion, and place, have a positive beta sign, proving that predictor variables have a positive effect on that of the predicting dependent variable marketing strategy practice. Even though the marketing strategies of the company are effectively practiced, there are some problems that the company faces while implementing them. These are infrastructure problems, economic problems, intensive competition in the market, shortage of raw materials, seasonality of consumption, socio-cultural problems, and the time and cost of awareness creation for the customers. Finally, the authors suggest that the company better develop a long-range view and try to implement a more structured approach to attain information about potential customers, competitor’s actions, and market intelligence within the industry. In addition, we recommend conducting the study by increasing the sample size and including different marketing factors.

Keywords: marketing strategy, market segmentation, target marketing, market positioning, marketing mix

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: Michael Aupetit, Mahmoud Al-ismail, Khaled Mohamed

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Cancer is a major public health problem all over the world. Breast cancer has the highest incidence rate over all cancers for women in Qatar making its study a top priority of the country. Human cancer is a dynamic disease that develops over an extended period through the accumulation of a series of genetic alterations. A Darwinian process drives the tumor cells toward higher malignancy growing the branches of a progression tree in the space of genes expression. Although it is not possible to track these genetic alterations dynamically for one patient, it is possible to reconstruct the progression tree from the aggregation of thousands of tumor cells’ genetic profiles from thousands of different patients at different stages of the disease. Analyzing the progression tree is a way to detect pivotal molecular events that drive the malignant evolution and to provide a guide for the development of cancer diagnostics, prognostics and targeted therapeutics. In this work we present the development of a Visual Analytic web platform CanVis enabling users to upload gene-expression data and analyze their progression tree. The server computes the progression tree based on state-of-the-art techniques and allows an interactive visual exploration of this tree and the gene-expression data along its branching structure helping to discover potential driver genes.

Keywords: breast cancer, progression tree, visual analytics, web platform

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Authors: Pranav Ajmera, Amit Kharat, Tanveer Gupte, Richa Pant, Viraj Kulkarni, Vinay Duddalwar, Purnachandra Lamghare

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The cardiothoracic ratio (CTR) is the ratio of the diameter of the heart to the diameter of the thorax. An abnormal CTR, that is, a value greater than 0.55, is often an indicator of an underlying pathological condition. The accurate prediction of an abnormal CTR from chest X-rays (CXRs) aids in the early diagnosis of clinical conditions. We propose a deep learning-based model for automatic CTR calculation that can assist the radiologist with the diagnosis of cardiomegaly and optimize the radiology flow. The study population included 1012 posteroanterior (PA) CXRs from a single institution. The Attention U-Net deep learning (DL) architecture was used for the automatic calculation of CTR. A CTR of 0.55 was used as a cut-off to categorize the condition as cardiomegaly present or absent. An observer performance test was conducted to assess the radiologist's performance in diagnosing cardiomegaly with and without artificial intelligence (AI) assistance. The Attention U-Net model was highly specific in calculating the CTR. The model exhibited a sensitivity of 0.80 [95% CI: 0.75, 0.85], precision of 0.99 [95% CI: 0.98, 1], and a F1 score of 0.88 [95% CI: 0.85, 0.91]. During the analysis, we observed that 51 out of 1012 samples were misclassified by the model when compared to annotations made by the expert radiologist. We further observed that the sensitivity of the reviewing radiologist in identifying cardiomegaly increased from 40.50% to 88.4% when aided by the AI-generated CTR. Our segmentation-based AI model demonstrated high specificity and sensitivity for CTR calculation. The performance of the radiologist on the observer performance test improved significantly with AI assistance. A DL-based segmentation model for rapid quantification of CTR can therefore have significant potential to be used in clinical workflows.

Keywords: cardiomegaly, deep learning, chest radiograph, artificial intelligence, cardiothoracic ratio

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Authors: Asha Dukkipati

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Cognitive neuroscience explores neural functioning and aberrant brain activity during cognitive and perceptual tasks. Neurocinematics is a subfield of cognitive neuroscience that observes neural responses of individuals watching a film to see similarities and differences between individuals. This method is typically used for commercial use, allowing directors and filmmakers to produce better visuals and increasing their results in the box office. However, neurocinematics is increasingly becoming a common tool for neuroscientists interested in studying similar patterns of brain activity across viewers outside of the film industry. In this review, it argue that neurocinematics provides an easy, naturalistic approach for studying and diagnosing learning disorders. While the neural underpinnings of developmental learning disorders are traditionally assessed with well-established methods like EEG and fMRI that target particular cognitive domains, such as simple visual and attention tasks, there is initial evidence and theoretical background in support of neurocinematics as a biomarker for learning differences. By using ADHD, dyslexia, and autism as case studies, this literature review discusses the potential advantages of neurocinematics as a new tool for learning disorders research.

Keywords: behavioral and social sciences, neuroscience, neurocinematics, biomarkers, neurobehavioral disorders

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Authors: Julia Brudzinski, Ashley Croswell, Jade Mardin, Hannah Shilling, Jennifer Berg-Carnegie

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Adults with brain injuries and mental illnesses commonly experience cognitive impairments that interfere with their participation in activities of daily living (ADLs). Prior research states that electronic reminder systems can support adults with cognitive impairments; however, previous studies focus primarily on one-way reminder systems. Research on adults with chronic diseases reported that two-way reminder systems yield better health outcomes and disease self-management compared to one-way reminder systems. Literature was identified through systematically searching 7 databases and hand-searching relevant reference lists. Retrieved studies were independently screened and reviewed by at least two members of the research team. Data was extracted on study design, participant characteristics, intervention details, study objectives, outcome measures, and important results. 574 articles were screened and reviewed. Nine articles met all inclusion criteria and were included. The literature focused on three main areas: system feasibility (n=8), stakeholder satisfaction (n=6), and efficacy of the two-way reminder systems (n=6). Participants in eight of the studies had brain injuries, with participants in only one study having a mental illness (i.e., schizophrenia). Two-way reminder systems were used to support participation in a wide range of ADLs. The current literature on two-way reminder systems to support ADLs for adults with cognitive impairments focuses on feasibility, stakeholder satisfaction, and system efficacy. Future research should focus on addressing the barriers to accessing and implementing two-way reminder systems and identifying specific client characteristics that would benefit most from using these systems.

Keywords: brain injury, digital health, occupational therapy, activities of daily living, two-way reminder systems

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Authors: Susan Amirsalari, Azime Khosrinejad, Elham Rahimian

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Objective: Epilepsy is a common brain disorder characterized by a persistent tendency to develop in neurological, cognitive, and psychological contents. Magnetic Resonance Imaging (MRI) is a neuroimaging test facilitating the detection of structural epileptogenic lesions. This study aimed to compare the MRI findings between patients with intractable and drug-responsive epilepsy. Material & methods: This case-control study was conducted from 2007 to 2019. The research population encompassed all 1-16- year-old patients with intractable epilepsy referred to the Shafa Neuroscience Center (n=72) (a case group) and drug-responsive patients referred to the pediatric neurology clinic of Baqiyatallah Hospital (a control group). Results: There were 72 (23.5%) patients in the intractable epilepsy group and 200 (76.5%) patients in the drug-responsive group. The participants' mean age was 6.70 ±4.13 years, and there were 126 males and 106 females in this study Normal brain MRI was noticed in 21 (29.16%) patients in the case group and 184 (92.46%) patients in the control group. Neuronal migration disorder (NMD)was also exhibited in 7 (9.72%) patients in the case group and no patient in the control group. There were hippocampal abnormalities and focal lesions (mass, dysplasia, etc.) in 10 (13.88%) patients in the case group and only 1 (0.05%) patient in the control group. Gliosis and porencephalic cysts were presented in 3 (4.16%) patients in the case group and no patient in the control group. Cerebral and cerebellar atrophy was revealed in 8 (11.11%) patients in the case group and 4 (2.01%) patients in the control group. Corpus callosum agenesis, hydrocephalus, brain malacia, and developmental cyst were more frequent in the case group; however, the difference between the groups was not significant. Conclusion: The MRI findings such as hippocampal abnormalities, focal lesions (mass, dysplasia), NMD, porencephalic cysts, gliosis, and atrophy are significantly more frequent in children with intractable epilepsy than in those with drug-responsive epilepsy.

Keywords: magnetic resonance imaging, intractable epilepsy, drug responsive epilepsy, neuronal migrational disorder

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Authors: Yuri V. Bykov, V. A. Baturin

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Aim of the study: The aim of the study was to perform a comparative analysis of the levels of autoantibodies (AAB) to the S-100 protein as well as to the dopamine and NMDA receptors in children with type 1 diabetes mellitus (DM) in therapeutic remission. Materials and methods: Blood serum obtained from 42 children ages 4 to 17 years (20 boys and 22 girls) was analyzed. Twenty-one of these children had a diagnosis of type 1 DM and were in therapeutic remission (study group). The mean duration of disease in children with type 1 DM was 9.6±0.36 years. Children without DM were included in a group of "apparently healthy children" (21 children, comparison group). AAB to the S-100 protein, the dopamine, and NMDA receptors were measured by ELISA. The normal range of IgG AAB was specified as up to 10 µg/mL. In order to compare the central parameters of the groups, the following parametric and non-parametric methods were used: Student's t-test or Mann-Whitney U test. The level of significance for inter-group comparisons was set at p<0.05. Results: The mean levels of AAB to the S-100B protein were significantly higher (p=0.0045) in children with DM (16.84±1.54 µg/mL) when compared with "apparently healthy children" (2.09±0.05 µg/mL). The detected elevated levels of AAB to NMDA receptors may indicate that in children with type 1 DM, there is a change in the activity of the glutamatergic system, which in its turn suggests the presence of excitotoxicity. The mean levels of AAB to dopamine receptors were higher (p=0.0082) in patients comprising the study group than in the children of the comparison group (40.47±2.31 µg/mL and 3.91±0.09 µg/mL). The detected elevated levels of AAB to dopamine receptors suggest an altered activity of the dopaminergic system in children with DM. This can also be viewed as indirect evidence of altered activity of the brain's glutamatergic system. The mean levels of AAB to NMDA receptors were higher in patients with type 1 DM compared with the "apparently healthy children," at 13.16±2.07 µg/mL and 1.304±0.05 µg/mL, respectively (p=0.0021). The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in children with type 1 DM. A difference was also detected between the mean values of the measured AABs, and this difference depended on the duration of the disease: mean AAB values were significantly higher in patients whose disease had lasted more than five years. Conclusions: The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in the setting of excitotoxicity in children with type 1 DM. The discovered elevation of the levels of AAB to NMDA and dopamine receptors may indicate the activation of the glutamatergic and dopaminergic systems. The observed abnormalities indicate the presence of central nervous system damage in children with type 1 DM, with a tendency towards the elevation of the levels of the studied AABs with disease progression.

Keywords: autoantibodies, brain damage, children, diabetes mellitus

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Authors: Suliman Khan, Rabeea Siddique, Mengzhou Xue

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Background: Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease, including cancer, psychiatric, and related brain diseases. In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice’s brains. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the qPCR analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL. Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.

Keywords: chronic jetlag, molecular profiles, brain disorders, circadian rhythms

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Authors: Roudabeh Vakil Monfared, Farhad Mashayekhi

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Breast cancer is the most common malignancy type among women with about 1 million new cases each year. The immune system plays an important role in the breast cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a member of the tumor necrosis factor super family binds to its receptor OX40 and this co-stimulation has a crucial role in T-cell proliferation, survival and cytokine release. Due to the importance of the T-cells in anti-tumor activities of OX40L we studied the association of rs3850641 (T→C) polymorphism of OX40L gene with breast cancer. The study included 123 women with breast cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was extracted from blood leucocytes. Genotype and allele frequencies were determined in patients and control cases with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the analysis was performed by Med Calc. The prevalence of genotype frequencies of TT, CT and CC were 60.9%, 30.08% and 8.9 % in patients with breast cancer and 74.6 %, 18.25 % and 7.14 % in healthy volunteers while the T and C allelic frequency was 76.01% and 23.98 % in patients and 83.73% and 16.26% in healthy controls. Respectively Statistical analysis has shown no significant difference from the comparison of either genotype (P=0.06). According to these results, the rs3850641 SNP has no association with the susceptibility of breast cancer in a population in northern Iran. However, further studies in larger populations including other genetic and environmental factors are required to achieve conclusion.

Keywords: OX40L, gene, polymorphism, breast cancer

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Authors: Saba Fahham, Supak Ngamsom, Suchaya Damrongsri

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Objective: The objective is to determine the optimal threshold of Romexis software for the airway volume and minimum cross-section area (MCA) analysis using Image J as a gold standard. Materials and Methods: A total of ten cone-beam computed tomography (CBCT) images were collected. The airway volume and MCA of each patient were analyzed using the automatic airway segmentation function in the CBCT DICOM viewer (Romexis). Airway volume and MCA measurements were conducted on each CBCT sagittal view with fifteen different threshold values from the Romexis software, Ranging from 300 to 1000. Duplicate DICOM files, in axial view, were imported into Image J for concurrent airway volume and MCA analysis as the gold standard. The airway volume and MCA measured from Romexis and Image J were compared using a t-test with Bonferroni correction, and statistical significance was set at p<0.003. Results: Concerning airway volume, thresholds of 600 to 850 as well as 1000, exhibited results that were not significantly distinct from those obtained through Image J. Regarding MCA, employing thresholds from 400 to 850 within Romexis Viewer showed no variance from Image J. Notably, within the threshold range of 600 to 850, there were no statistically significant differences observed in both airway volume and MCA analyses, in comparison to Image J. Conclusion: This study demonstrated that the utilization of Planmeca Romexis Viewer 6.4.3.3 within threshold range of 600 to 850 yields airway volume and MCA measurements that exhibit no statistically significant variance in comparison to measurements obtained through Image J. This outcome holds implications for diagnosing upper airway obstructions and post-orthodontic surgical monitoring.

Keywords: airway analysis, airway segmentation, cone beam computed tomography, threshold

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

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Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: Abdollah Aliesmaeili

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The purpose of this research is to present a different perspective on the basic math teaching method called meta-instruction, which reverses the learning path. Meta-instruction is a method of teaching in which the teaching trajectory starts from brain education into learning. This research focuses on the behavior of the mind during learning. In this method, students are not instructed in mathematics, but they are educated. Another goal of the research is to "criticize Bloom's classification in the cognitive domain and reverse it", because it cannot meet the educational and instructional needs of the new generation and "substituting math education instead of math teaching". This is an indirect method of teaching. The method of research is longitudinal through four years. Statistical samples included students ages 6 to 11. The research focuses on improving the mental abilities of children to explore mathematical rules and operations by playing only with eight measurements (any years 2 examinations). The results showed that there is a significant difference between groups in remembering, understanding, and applying. Moreover, educating math is more effective than instructing in overall learning abilities.

Keywords: applying, Bloom's taxonomy, brain education, mathematics teaching method, meta-instruction, remembering, starmath method, understanding

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Pawan Kumar Gupta, Sumana Ghosh

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Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Andreia Guimaraes Farnese, Mateus Fernandes Reu Urban, Leandro Procopio, Renato Zangaro, Regiane Albertini

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Senescence changes include postural balance, inferring the risk of falls, and can lead to fractures, bedridden, and the risk of death. Physical activity, e.g., cardiovascular exercises, is notable for improving balance due to brain cell stimulations, but fine coordination exercises also elevate cell brain metabolism. This study aimed to verify whether the elderly person who performs fine motor activity has a balance similar to that of those who practice physical activity. The subjects were divided into three groups according to the activity practice: control group (CG) with seven participants for the sedentary individuals, motor coordination group (MCG) with six participants, and activity practitioner group (PAG) with eight participants. Data comparisons were from the Berg balance scale, Time up and Go test, and stabilometric analysis. Descriptive statistical and ANOVA analyses were performed for data analysis. The results reveal that including fine motor activities can improve the balance of the elderly and indirectly decrease the risk of falls.

Keywords: balance, barapodometer, coordination, elderly

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