Search results for: arterial progression

Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani

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Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.

Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.

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Authors: Tahir Majeed, Michael Handschuh, René Meier

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Rheumatoid arthritis patients have swelling and pain at the joints of the hand. The regions where the patient feels pain also show increased body temperature. Thermal cameras can be used to detect the rise in temperature of the affected regions. To monitor the disease progression of rheumatoid arthritis patients, they must visit the clinic regularly for scanning and examination. After scanning and evaluation, the dosage of the medicine is regulated accordingly. To monitor the disease progression over time, the correlation between the images between different visits must be established. It has been observed that by using low-cost thermal cameras, the thermal measurements do not remain the same over time, even within a single scanning. In some situations, temperatures can vary as much as 2°C within the same scanning sequence. In this paper, it has been shown that although the absolute temperature varies over time, the relative difference between the different regions remains similar. Results have been computed over four scanning sequences and are presented.

Keywords: relative thermal difference, rheumatoid arthritis, thermal imaging, thermal sensors

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Authors: Eunhye Cho, Hyuk-Hoon Kim, Sieun Lee, Minjung Kathy Chae

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Introduction: I-gel is a commonly used supraglottic advanced airway device in prehospital out-of-hospital cardiac arrest (OHCA) allowing for minimal interruption of continuous chest compression. However, previous studies have shown that prehospital supraglottic airway had inferior neurologic outcomes and survival compared to no advanced prehospital airway with conventional bag mask ventilation. We hypothesize that continuous compression with i-gel as an advanced airway may cause insufficient ventilation compared to 30:2 chest compression with conventional BVM. Therefore, we investigated the ventilation efficacy of i-gel with the initial arterial blood gas analysis in OHCA patients visiting our ER. Material and Method: Demographics, arrest parameters including i-gel insertion, initial arterial blood gas analysis was retrospectively analysed for 119 transported OHCA patients that visited our ER. Linear regression was done to investigate the association with i-gel insertion and initial pCO2 as a surrogate of prehospital ventilation. Result: A total of 52 patients were analysed for the study. Of the patients who visited the ER during OHCA, 24 patients had i-gel insertion and 28 patients had BVM as airway management in the prehospital phase. Prehospital i-gel insertion was associated with the initial pCO2 level (B coefficient 29.9, SE 10.1, p<0.01) after adjusting for bystander CPR, cardiogenic cause of arrest, EMS call to arrival. Conclusion: Despite many limitations to the study, prehospital insertion of i-gel was associated with high initial pCO2 values in OHCA patients visiting our ER, possibly indicating insufficient ventilation with prehospital i-gel as an advanced airway and continuous chest compressions.

Keywords: arrest, I-gel, prehospital, ventilation

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Authors: Sungpil Ha, Ju Yong Kang, Sangbaek Park, Seung-Ju Lee, Soo-Won Chae

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The growing number of obese patients in aging societies has led to an increase in the number of patients with knee medial osteoarthritis (OA). Artificial joint insertion is the most common treatment for knee medial OA. Surgery is effective for patients with serious arthritic symptoms, but it is costly and dangerous. It is also inappropriate way to prevent a disease as an early stage. Therefore Non-operative treatments such as toe-in gait are proposed recently. Toe-in gait is one of non-surgical interventions, which restrain the progression of arthritis and relieves pain by reducing knee adduction moment (KAM) to facilitate lateral distribution of load on to knee medial cartilage. Numerous studies have measured KAM in various foot progression angle (FPA), and KAM data could be obtained by motion analysis. However, variations in stress at knee cartilage could not be directly observed or evaluated by these experiments of measuring KAM. Therefore, this study applied motion analysis to major gait points (1st peak, mid –stance, 2nd peak) with regard to FPA, and to evaluate the effects of FPA on the human lower extremity, the finite element (FE) method was employed. Three types of gait analysis (toe-in, toe-out, baseline gait) were performed with markers placed at the lower extremity. Ground reaction forces (GRF) were obtained by the force plates. The forces associated with the major muscles were computed using GRF and marker trajectory data. MRI data provided by the Visible Human Project were used to develop a human lower extremity FE model. FE analyses for three types of gait simulations were performed based on the calculated muscle force and GRF. We observed the maximum stress point during toe-in gait was lower than the other types, by comparing the results of FE analyses at the 1st peak across gait types. This is the same as the trend exhibited by KAM, measured through motion analysis in other papers. This indicates that the progression of knee medial OA could be suppressed by adopting toe-in gait. This study integrated motion analysis with FE analysis. One advantage of this method is that re-modeling is not required even with changes in posture. Therefore another type of gait simulation or various motions of lower extremity can be easily analyzed using this method.

Keywords: finite element analysis, gait analysis, human model, motion capture

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Authors: Abeer Ahmed Abdelhamed

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Introduction: Postoperative pulmonary complications (PPCs) are the most common complications observed and managed after abdominal or cardiothoracic surgery. Hypoxemia, atelectasis, pleural effusion, or diaphragmatic dysfunction, are often a source of morbidity in cardiac surgery patients, and are more common in patients receiving unilateral or bilateral internal mammary artery (IMT) grafts than patients receiving saphenous vein (SV) grafts alone. Purpose: The aim of this work was to investigate the effect of Threshold load inspiratory muscle training on pulmonary gas exchange and maximum inspiratory pressure (MIP) in patient undergoing coronary revascularization. Subject: Thirty three male patients eligible for coronary revascularization were selected to participate in the study. Method: They were divided into two groups(17 patients in the intervention group and 16 patients in the control group), the interventional group received inspiratory muscle training at 30% of their maximum inspiratory pressure throughout the hospitalization period in addition to routine post operative care. Result: The results of this study showed a significant improvement on maximum inspiratory pressure(MIP), Arterial-alveolar pressure gradient (A-a gradient) and oxygen saturation in the intervention group. Conclusion: Inspiratory muscle training using threshold mode significantly improves maximum inspiratory pressure, pulmonary gas exchange tested by alveolar-arterial gradient and oxygen saturation in Patients undergoing coronary revascularization.

Keywords: coronary revascularization, inspiratory muscle training, maximum inspiratory pressure, pulmonary gas exchange

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Authors: Chia-Feng Lu, Yuh-Jen Wang, Yu-Te Wu, Sui-Hing Yan

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This study aimed at investigating whether the functional brain networks constructed using the initial EEG (obtained when patients first visited hospital) can be correlated with the progression of cognitive decline calculated as the changes of mini-mental state examination (MMSE) scores between the latest and initial examinations. We integrated the time–frequency cross mutual information (TFCMI) method to estimate the EEG functional connectivity between cortical regions, and the network analysis based on graph theory to investigate the organization of functional networks in aMCI. Our finding suggested that higher integrated functional network with sufficient connection strengths, dense connection between local regions, and high network efficiency in processing information at the initial stage may result in a better prognosis of the subsequent cognitive functions for aMCI. In conclusion, the functional connectivity can be a useful biomarker to assist in prediction of cognitive declines in aMCI.

Keywords: cognitive decline, functional connectivity, MCI, MMSE

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Authors: Bruno RamaëL, GwenaëL Page, Catherine Knopf-Lenoir, Olivier Baledent, Anne-Virginie Salsac

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No routine technique currently exists for clinicians to measure the mechanical properties of vascular walls non-invasively. Most of the data available in the literature come from traction or dilatation tests conducted ex vivo on native blood vessels. The objective of the study is to develop a non-invasive characterization technique based on Magnetic Resonance Imaging (MRI) measurements of the deformation of vascular walls under pulsating blood flow conditions. The goal is to determine the mechanical properties of the vessels by inverse analysis, coupling imaging measurements and numerical simulations of the fluid-structure interactions. The hyperelastic properties are identified using Solidworks and Ansys workbench (ANSYS Inc.) solving an optimization technique. The vessel of interest targeted in the study is the common carotid artery. In vivo MRI measurements of the vessel anatomy and inlet velocity profiles was acquired along the facial vascular network on a cohort of 30 healthy volunteers: - The time-evolution of the blood vessel contours and, thus, of the cross-section surface area was measured by 3D imaging angiography sequences of phase-contrast MRI. - The blood flow velocity was measured using a 2D CINE MRI phase contrast (PC-MRI) method. Reference arterial pressure waveforms were simultaneously measured in the brachial artery using a sphygmomanometer. The three-dimensional (3D) geometry of the arterial network was reconstructed by first creating an STL file from the raw MRI data using the open source imaging software ITK-SNAP. The resulting geometry was then transformed with Solidworks into volumes that are compatible with Ansys softwares. Tetrahedral meshes of the wall and fluid domains were built using the ANSYS Meshing software, with a near-wall mesh refinement method in the case of the fluid domain to improve the accuracy of the fluid flow calculations. Ansys Structural was used for the numerical simulation of the vessel deformation and Ansys CFX for the simulation of the blood flow. The fluid structure interaction simulations showed that the systolic and diastolic blood pressures of the common carotid artery could be taken as reference pressures to identify the mechanical properties of the different arteries of the network. The coefficients of the hyperelastic law were identified using Ansys Design model for the common carotid. Under large deformations, a stiffness of 800 kPa is measured, which is of the same order of magnitude as the Young modulus of collagen fibers. Areas of maximum deformations were highlighted near bifurcations. This study is a first step towards patient-specific characterization of the mechanical properties of the facial vessels. The method is currently applied on patients suffering from facial vascular malformations and on patients scheduled for facial reconstruction. Information on the blood flow velocity as well as on the vessel anatomy and deformability will be key to improve surgical planning in the case of such vascular pathologies.

Keywords: identification, mechanical properties, arterial walls, MRI measurements, numerical simulations

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Authors: Jeoffrey Oostrom, Robbert James Schlingmann, Hani Alers

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This document depicts the research into the indicators of dementia progression, the automation of quality of life assignments, and the visualization of it. To do this, the Smart Teddy project was initiated to make a smart companion that both monitors the senior citizen as well as processing the captured data into an insightful dashboard. With around 50 million diagnoses worldwide, dementia proves again and again to be a bothersome strain on the lives of many individuals, their relatives, and society as a whole. In 2015 it was estimated that dementia care cost 818 billion U.S Dollars globally. The Smart Teddy project aims to take away a portion of the burden from caregivers by automating the collection of certain data, like movement, geolocation, and sound-levels. This paper proves that the Smart Teddy has the potential to become a useful tool for caregivers but won’t pose as a solution. The Smart Teddy still faces some problems in terms of emotional privacy, but its non-intrusive nature, as well as diversity in usability, can make up for it.

Keywords: dementia care, medical data visualization, quality of life, smart companion

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Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

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Authors: Lorena Mihelac, Janez Povh

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In 2017, we conducted a research study using data consisting of 160 musical excerpts from different musical styles, to analyze the impact of entropy of the harmony on the acceptability of music. In measuring the entropy of harmony, we were interested in unigrams (individual chords in the harmonic progression) and bigrams (the connection of two adjacent chords). In this study, it has been found that 53 musical excerpts out from 160 were evaluated by participants as very complex, although the entropy of the harmonic progression (unigrams and bigrams) was calculated as low. We have explained this by particularities of chord progression, which impact the listener's feeling of complexity and acceptability. We have evaluated the same data twice with new participants in 2018 and with the same participants for the third time in 2019. These three evaluations have shown that the same 53 musical excerpts, found to be difficult and complex in the study conducted in 2017, are exhibiting a high feeling of complexity again. It was proposed that the content of these musical excerpts, defined as “irregular,” is not meeting the listener's expectancy and the basic perceptual principles, creating a higher feeling of difficulty and complexity. As the “irregularities” in these 53 musical excerpts seem to be perceived by the participants without being aware of it, affecting the pleasantness and the feeling of complexity, they have been defined as “subliminal irregularities” and the 53 musical excerpts as “irregular.” In our recent study (2019) of the same data (used in previous research works), we have proposed a new measure of the complexity of harmony, “regularity,” based on the irregularities in the harmonic progression and other plausible particularities in the musical structure found in previous studies. We have in this study also proposed a list of 10 different particularities for which we were assuming that they are impacting the participant’s perception of complexity in harmony. These ten particularities have been tested in this paper, by extending the analysis in our 53 irregular musical excerpts from harmony to melody. In the examining of melody, we have used the computational model “Information Dynamics of Music” (IDyOM) and two information-theoretic measures: entropy - the uncertainty of the prediction before the next event is heard, and information content - the unexpectedness of an event in a sequence. In order to describe the features of melody in these musical examples, we have used four different viewpoints: pitch, interval, duration, scale degree. The results have shown that the texture of melody (e.g., multiple voices, homorhythmic structure) and structure of melody (e.g., huge interval leaps, syncopated rhythm, implied harmony in compound melodies) in these musical excerpts are impacting the participant’s perception of complexity. High information content values were found in compound melodies in which implied harmonies seem to have suggested additional harmonies, affecting the participant’s perception of the chord progression in harmony by creating a sense of an ambiguous musical structure.

Keywords: entropy and information content, harmony, subliminal (ir)regularity, IDyOM

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Authors: Wu Peng, Anders Liljerehn, Martin Magnevall

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In metal cutting, tool wear gradually changes the micro geometry of the cutting edge. Today there is a significant gap in understanding the impact these geometrical changes have on the cutting forces which governs tool deflection and heat generation in the cutting zone. Accurate models and understanding of the interaction between the work piece and cutting tool leads to improved accuracy in simulation of the cutting process. These simulations are useful in several application areas, e.g., optimization of insert geometry and machine tool monitoring. This study aims to develop an extended Kienzle force model to account for the effect of rake angle variations and tool flank wear have on the cutting forces. In this paper, the starting point sets from cutting force measurements using orthogonal turning tests of pre-machined flanches with well-defined width, using triangular coated inserts to assure orthogonal condition. The cutting forces have been measured by dynamometer with a set of three different rake angles, and wear progression have been monitored during machining by an optical measuring collaborative robot. The method utilizes the measured cutting forces with the inserts flank wear progression to extend the mechanistic cutting forces model with flank wear as an input parameter. The adapted cutting forces model is validated in a turning process with commercial cutting tools. This adapted cutting forces model shows the significant capability of prediction of cutting forces accounting for tools flank wear and different-rake-angle cutting tool inserts. The result of this study suggests that the nonlinear effect of tools flank wear and interaction between the work piece and the cutting tool can be considered by the developed cutting forces model.

Keywords: cutting force, kienzle model, predictive model, tool flank wear

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Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

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S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

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Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human endogenous retrovirus (HERV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on HERV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", "Human endogenous retrovirus", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles chosen, studied, and analyzed. Results: In the leptomeningeal cells of MS patients, a retrovirus-like element associated with reverse transcriptase (RT) activity called multiple sclerosis-associated retroviruses (MSRV) has been identified. HERVs are expressed in the human CNS despite mechanisms to suppress their expression. External factors, especially viral infections such as influenza virus, Epstein-Barr virus, and herpes simplex virus type 1, can activate HERV gene expression. The MSRV coat protein is activated by activating TLR4 at the brain surface, particularly in oligodendroglial progenitor cells and macrophages, leading to immune cascades followed by the downregulation of myelin protein expression. The HERV-K18 envelope gene (env) acts as a superantigen and induces inflammatory responses in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HERV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of endogenous retroviruses may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human endogenous retrovirus, central nervous system, MSRV

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Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

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Background: Long non-coding RNAs (lncRNAs) are the important regulators of gene expression and play important role in viral replication and disease progression. The role of lncRNA genes in the pathogenesis of Dengue virus-mediated pathogenesis is currently unknown. Methods: To gain additional insights, we utilized an unbiased RNA sequencing followed by in silico analysis approach to identify the differentially expressed lncRNA and genes that are associated with dengue disease progression. Further, we focused our study on lncRNAs NEAT1 (Nuclear Paraspeckle Assembly Transcript 1) as it was found to be differentially expressed in PBMC of dengue infected patients. Results: The expression of lncRNAs NEAT1, as compared to dengue infection (DI), was significantly down-regulated as the patients developed the complication. Moreover, pairwise analysis on follow up patients confirmed that suppression of NEAT1 expression was associated with rapid fall in platelet count in dengue infected patients. Severe dengue patients (DS) (n=18; platelet count < 20K) when recovered from infection showing high NEAT1 expression as it observed in healthy donors. By co-expression network analysis and subsequent validation, we revealed that coding gene; IFI27 expression was significantly up-regulated in severe dengue cases and negatively correlated with NEAT1 expression. To discriminate DI from dengue severe, receiver operating characteristic (ROC) curve was calculated. It revealed sensitivity and specificity of 100% (95%CI: 85.69 – 97.22) and area under the curve (AUC) = 0.97 for NEAT1. Conclusions: Altogether, our first observations demonstrate that monitoring NEAT1and IFI27 expression in dengue patients could be useful in understanding dengue virus-induced disease progression and may be involved in pathophysiological processes.

Keywords: dengue, lncRNA, NEAT1, transcriptome

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: Sohrab Jafarpour, Hamed Farokhi, Mohammad Rahmati, Alireza Gholipour

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In the current study, a nonlinear fluid-structure interaction (FSI) biomechanical model of atherosclerosis in the left anterior descending (LAD) coronary artery is developed to perform a detailed sensitivity analysis of the geometrical features of an atheroma plaque. In the development of the numerical model, first, a 3D geometry of the diseased artery is developed based on patient-specific dimensions obtained from the experimental studies. The geometry includes four influential geometric characteristics: stenosis ratio, plaque shoulder-length, fibrous cap thickness, and eccentricity intensity. Then, a suitable strain energy density function (SEDF) is proposed based on the detailed material stability analysis to accurately model the hyperelasticity of the arterial walls. The time-varying inlet velocity and outlet pressure profiles are adopted from experimental measurements to incorporate the pulsatile nature of the blood flow. In addition, a computationally efficient type of structural boundary condition is imposed on the arterial walls. Finally, a non-Newtonian viscosity model is implemented to model the shear-thinning behaviour of the blood flow. According to the results, the structural responses in terms of the maximum principal stress (MPS) are affected more compared to the fluid responses in terms of wall shear stress (WSS) as the geometrical characteristics are varying. The extent of these changes is critical in the vulnerability assessment of an atheroma plaque.

Keywords: atherosclerosis, fluid-Structure interaction modeling, material stability analysis, and nonlinear biomechanics

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Authors: Yishu Gong, Liangliang Yang, Jianyu Zhang, Zhengyu Chen, Sihong He, Xusheng Zhang, Wei Zhang

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide and is characterized by cognitive decline and behavioral changes. People living with Alzheimer’s disease often find it hard to complete routine tasks. However, there are limited objective assessments that aim to quantify the difficulty of certain tasks for AD patients compared to non-AD people. In this study, we propose to use speech emotion recognition (SER), especially the frustration level, as a potential biomarker for quantifying the difficulty patients experience when describing a picture. We build an SER model using data from the IEMOCAP dataset and apply the model to the DementiaBank data to detect the AD/non-AD group difference and perform longitudinal analysis to track the AD disease progression. Our results show that the frustration level detected from the SER model can possibly be used as a cost-effective tool for objective tracking of AD progression in addition to the Mini-Mental State Examination (MMSE) score.

Keywords: Alzheimer’s disease, speech emotion recognition, longitudinal biomarker, machine learning

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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Authors: Natalie Preville, Carlos Joel Mejia-Olivares

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In the UK, since the early 1950s when the NHS was founded, international staff in the NHS have played an important role. Currently, they represent 16% of the workforce within the NHS in the UK. Furthermore, to address the shortfalls in nursing staff, international recruitment programs have been essential to reduce the gaps in the UK nursing workforce over the last two decades. The NHS Long Term Plan (2019) aims to have a significant reduction of nursing vacancies to 5% by 2028. However, in 2021 and 2022, Workforce Race Equality Standards (WRES) reports stated that there is inequitable Career Progression (CP) among Internationally Recruited (IR) nurses as compared to British counterparts. In addition, there is sufficient literature exploring the motives and lived experiences of IR nurses, which underpins the findings. Therefore, the overall aim of this report is to conduct a scoping project to understand the experiences of the IR nurses who joined the NHS in the South East of England within the last 5 years. Methodology- This document is based on the data from a survey developed by Royal Berkshire NHS Foundation Trust using Microsoft forms and consisted of 23 questions divided into four themes, staff background, career experience, career progression and future career plans within Royal Berkshire NHS Foundation Trust. The descriptive analysis provided the initial analysis of the quantitative data. As a result, 44 responses were collected and evaluated by utilising Microsoft excel. Key findings: Career experiences; 72% of respondents felt that their current role was a good fit, and in a subsequent question, the main reason cited was having “relevant skills”. This indicates that, for the most part, the prior experience of IR nurses is a large factor in their placement, which is viewed positively; the next step is to effectively apply similar relevance in aligning prior experience with career progression opportunities. Moreover, 67% of respondents feel valued by the department/team, which is a great reflection of the values of the Trust being demonstrated towards IR Nurses. However, further studies may be necessary to explore the reasons why the remaining 33% may not feel valued; this can include having a better understanding of cultural perceptions of value. Perceived Barriers: Although 37% of respondents had been promoted since commencing employment with the Trust, the data indicates that there is still room for CP opportunities, as it is the leading barrier reported by the respondents. Secondly, the growing mix of cultures within the nursing workforce gives the appearance of inclusion. However, this is not the experience of some IR nurses. Conclusion statemen: Survey results indicate that this NHS Trust has an excellent foundation to integrate international nurses into their workforce with scope for career progression in a reasonable timeframe. However, it would be recommendable to include fast-tracking career promotions by recognizing previous studies and professional experience. Further exploration of staff career experiences and goals may provide additional useful data for future planning.

Keywords: career progression, International nurses, perceived barriers, staff survey

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Authors: Cassandra Hansen, Paul Doherty, Chris Ferner, German Whitley, Holly Torpey

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Wildfire is a natural and inevitable occurrence, yet changing climatic conditions have increased the severity, frequency, and risk to human populations in the wildland/urban interface (WUI) of the Western United States. Rapid dissemination of accurate wildfire information is critical to both the Incident Management Team (IMT) and the affected community. With the advent of increasingly sophisticated information systems, GIS can now be used as a web platform for sharing geographic information in new and innovative ways, such as virtual story map applications. Crowdsourced information can be extraordinarily useful when coupled with authoritative information. Information abounds in the form of social media, emergency alerts, radio, and news outlets, yet many of these resources lack a spatial component when first distributed. In this study, we describe how twenty-eight volunteer GIS professionals across nine Geographic Area Coordination Centers (GACC) sourced, curated, and distributed Volunteered Geographic Information (VGI) from authoritative social media accounts focused on disseminating information about wildfires and public safety. The combination of fire progression maps with VGI incident information helps answer three critical questions about an incident, such as: where the first started. How and why the fire behaved in an extreme manner and how we can learn from the fire incident's story to respond and prepare for future fires in this area. By adding a spatial component to that shared information, this team has been able to visualize shared information about wildfire starts in an interactive map that answers three critical questions in a more intuitive way. Additionally, long-term social and technical impacts on communities are examined in relation to situational awareness of the disaster through map layers and agency links, the number of views in a particular region of a disaster, community involvement and sharing of this critical resource. Combined with a GIS platform and disaster VGI applications, this workflow and information become invaluable to communities within the WUI and bring spatial awareness for disaster preparedness, response, mitigation, and recovery. This study highlights progression maps as the ultimate storytelling mechanism through incident case studies and demonstrates the impact of VGI and sophisticated applied cartographic methodology make this an indispensable resource for authoritative information sharing.

Keywords: storytelling, wildfire progression maps, volunteered geographic information, spatial and temporal

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Authors: Hadj Abd El Kader Benghenia, Fethi Bereksi Reguig

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In clinical medicine, blood pressure, raised blood hemodynamic monitoring is rich pathophysiological information of cardiovascular system, of course described through factors such as: blood volume, arterial compliance and peripheral resistance. In this work, we are interested in analyzing these signals to propose a detection algorithm to delineate the different sequences and especially systolic blood pressure (SBP), diastolic blood pressure (DBP), and the wave and dicrotic to do their analysis in order to extract the cardiovascular parameters.

Keywords: blood pressure, SBP, DBP, detection algorithm

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Authors: Frank Boris Feutmba Keutchou, Saurelle Fabienne Bieghan Same, Verelle Elsa Fogang Pokam, Charles Ursula Metapi Meikeu, Angel Marilyne Messop Nzomo, Ousman Tamgue

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Infectious diseases are one of the most important causes of morbidity and mortality worldwide. These diseases are caused by micro-pathogenic organisms, such as bacteria, viruses, parasites, and fungi. Heritable changes in gene expression that do not involve changes to the underlying DNA sequence are referred to as epigenetics. Emerging evidence suggests that epigenetic mechanisms are important in the emergence and progression of infectious diseases. Pathogens can manipulate host epigenetic machinery to promote their own replication and evade immune responses. The Human Genome Project has provided new opportunities for developing better tools for the diagnosis and identification of target genes. Several epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression, have been shown to influence infectious disease outcomes. Understanding the epigenetic mechanisms underlying infectious diseases may result in the progression of new therapeutic approaches focusing on host-pathogen interactions. The goal of this study is to show how different infectious agents interact with host cells after infection.

Keywords: epigenetic, infectious disease, micro-pathogenic organism, phenotype

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Authors: G. Dadashova, A. Bakhshaliyev

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Aim: Determine gender differences in the etiology and clinical outcomes, as well as in the remodeling of the left ventricle (LV) in patients with chronic heart failure (CHF), suffering from arterial hypertension (AH) and coronary heart disease (CHD). Material and methods: The study included 112 patients of both sexes; aged 45 to 60 years with postinfarction cardiosclerosis had functional class (FC) heart failure II-IV of NYHA which were examined on the basis of Azerbaijan Scientific Research Institute of Cardiology. The patients were divided into 2 groups: 1st c. 60 males, mean age 54,8 ± 3,3 years, and 2nd gr 52 women, mean age 55,8 ± 3,1 years. To assess cardiac hemodynamic all patients underwent echocardiography (B-M-modes) using ‘Vivid 3’. Thus on the basis of indicators such as the index of the relative thickness of the left ventricle wall and the index of left ventricular mass (LVMI) was identified the architectonic model of the left ventricle. Results: According to our research leading cause of heart failure in women is 50.5% of cases of hypertension, ischemic heart disease 23.7% (with 79.5% of the cases developed in patients with chronic heart failure who did not have a history of myocardial infarction). While in men is the undisputed leader of CHD, forming 78.3% of CHF (80.3% in men with CHF occurred after myocardial infarction). According to our research in women more often than men CHF develops a type of diastolic dysfunction (DD, and left ventricular ejection fraction remained unchanged. Since DD occurs in men at 65,8% vs. 76,4% of women when p < 0,05. In the group of women was more common prognostic neblagopryatnye remodeling - eccentric hypertrophy of the left ventricle: 68% vs. 54.5% among men (p < 0,05), concentric left ventricular hypertrophy: 21% in women vs 19,1% (p > 0,05 ). Conclusions: Patients with heart failure are a number of gender-specific: the prevalence of hypertension in women, and coronary heart disease in men. While in women with heart failure often recorded diastolic dysfunction and characterized by the development of prognostically unfavorable remodeling types: eccentric and concentric LV hypertrophy.

Keywords: chronic heart failure, arterial hypertension, remodeling, diastolic dysfunction, men, women, ischemic heart disease

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Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

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Dengue virus infection is now considered as one of the most important mosquito-borne infection in human. The virus is known to promote vascular permeability, cerebral edema leading to Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Dengue infection has known to be endemic in India for over two centuries as a benign and self-limited disease. In the last couple of years, the disease symptoms have changed, manifesting severe secondary complication. So far, Delhi has experienced 12 outbreaks of dengue virus infection since 1997 with the last reported in 2014-15. Without specific antivirals, the case management of high-risk dengue patients entirely relies on supportive care, involving constant monitoring and timely fluid support to prevent hypovolemic shock. Nonetheless, the diverse clinical spectrum of dengue disease, as well as its initial similarity to other viral febrile illnesses, presents a challenge in the early identification of this high-risk group. WHO recommends the use of warning signs to identify high-risk patients, but warning signs generally appear during, or just one day before the development of severe illness, thus, providing only a narrow window for clinical intervention. The ability to predict which patient may develop DHF and DSS may improve the triage and treatment. With the recent discovery of high throughput RNA sequencing allows us to understand the disease progression at the genomic level. Here, we will collate the results of RNA-Sequencing data obtained recently from PBMC of different categories of dengue patients from India and will discuss the possible role of deregulated genes and long non-coding RNAs NEAT1 for development of disease progression.

Keywords: long non-coding RNA (lncRNA), dengue, peripheral blood mononuclear cell (PBMC), nuclear enriched abundant transcript 1 (NEAT1), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS)

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Authors: Lota Largavista

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This study entitled, ‘The Organizational Structure, Development Features, and Metadiscoursal Elements in the Expository Writing of Freshman College Writers’ aimed to examine essays written by college students. It seeks to examine the organizational structure and development features of the essays and describe their defining characteristics, the linguistic elements at both macrostructural and microstructural discourse levels and the types of textual and interpersonal metadiscourse markers that are employed in order to negotiate meanings with their prospective readers. The different frameworks used to analyze the essays include Toulmin’s ( 1984) model for argument structure, Olson’s ( 2003) three-part essay structure; Halliday and Matthiesen (2004) in Herriman (2011) notions of thematic structure, Danes (1974) thematic progression or method of development, Halliday’s (2004) concept of grammatical and lexical cohesion ;Hyland’s (2005) metadiscourse strategies; and Chung and Nation’s( 2003) four-step scale for technical vocabulary. This descriptive study analyzes qualitatively and quantitatively how freshman students generally express their written compositions. Coding of units is done to determine what linguistic features are present in the essays. Findings revealed that students’ expository essays observe a three-part structure having all three moves, the Introduction, the Body and the Conclusion. Stance assertion, stance support, and emerging moves/strategies are found to be employed in the essays. Students have more marked themes on the essays and also prefer constant theme progression as their method of development. The analysis of salient linguistic elements reveals frequently used cohesive devices and metadiscoursal strategies. Based on the findings, an instructional learning plan is being proposed. This plan is characterized by a genre approach that focuses on expository and linguistic conventions.

Keywords: metadiscourse, organization, theme progression, structure

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Authors: Chang Liang, Weizhi Gong, Yan Zhang

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Purpose: Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate and poor prognosis worldwide. Murine double minute 2 (MDM2) regulates the tumor suppressor p53, increasing cancer risk and accelerating tumor progression. Speckle-type POX virus and zinc finger protein (SPOP), a key of subunit of Cullin-Ring E3 ligase, inhibits tumor genesis and progression by the ubiquitination of its downstream substrates. This study aimed to clarify whether SPOP and MDM2 are mutually regulated in HCC and the correlation between SPOP and MDM2 and the prognosis of HCC patients. Methods: First, the expression of SPOP and MDM2 in HCC tissues were detected by TCGA database. Then, 53 paired samples of HCC tumor and adjacent tissues were collected to evaluate the expression of SPOP and MDM2 using immunohistochemistry. Chi-square test or Fisher’s exact test were used to analyze the relationship between clinicopathological features and the expression levels of SPOP and MDM2. In addition, Kaplan‒Meier curve analysis and log-rank test were used to investigate the effects of SPOP and MDM2 on the survival of HCC patients. Last, the Multivariate Cox proportional risk regression model analyzed whether the different expression levels of SPOP and MDM2 were independent risk factors for the prognosis of HCC patients. Results: Bioinformatics analysis revealed the low expression of SPOP and high expression of MDM2 were related to worse prognosis of HCC patients. The relationship between the expression of SPOP and MDM2 and tumor stem-like features showed an opposite trend. The immunohistochemistry showed the expression of SPOP protein was significantly downregulated while MDM2 protein significantly upregulated in HCC tissue compared to that in para-cancerous tissue. Tumors with low SPOP expression were related to worse T stage and Barcelona Clinic Liver Cancer (BCLC) stage, but tumors with high MDM2 expression were related to worse T stage, M stage, and BCLC stage. Kaplan–Meier curves showed HCC patients with high SPOP expression and low MDM2 expression had better survival than those with low SPOP expression and high MDM2 expression (P < 0.05). A multivariate Cox proportional risk regression model confirmed that a high MDM2 expression level was an independent risk factor for poor prognosis in HCC patients (P <0.05). Conclusion: The expression of SPOP protein was significantly downregulated, while the expression of MDM2 significantly upregulated in HCC. The low expression of SPOP and high expression. of MDM2 were associated with malignant progression and poor prognosis of HCC patients, indicating a potential therapeutic target for HCC patients.

Keywords: hepatocellular carcinoma, murine double minute 2, speckle-type POX virus and zinc finger protein, ubiquitination

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Authors: Houman Tamaddon, Mehrdad Behnia, Masud Behnia

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An accurate study of blood flow is associated with an accurate vascular pattern and geometrical properties of the organ of interest. Due to the complexity of vascular networks and poor accessibility in vivo, it is challenging to reconstruct the entire vasculature of any organ experimentally. The objective of this study is to introduce an innovative approach for the reconstruction of a full vascular tree from available morphometric data. Our method consists of implementing morphometric data on those parts of the vascular tree that are smaller than the resolution of medical imaging methods. This technique reconstructs the entire arterial tree down to the capillaries. Vessels greater than 2 mm are obtained from direct volume and surface analysis using contrast enhanced computed tomography (CT). Vessels smaller than 2mm are reconstructed from available morphometric and distensibility data and rearranged by applying Murray’s Laws. Implementation of morphometric data to reconstruct the branching pattern and applying Murray’s Laws to every vessel bifurcation simultaneously, lead to an accurate vascular tree reconstruction. The reconstruction algorithm generates full arterial tree topography down to the first capillary bifurcation. Geometry of each order of the vascular tree is generated separately to minimize the construction and simulation time. The node-to-node connectivity along with the diameter and length of every vessel segment is established and order numbers, according to the diameter-defined Strahler system, are assigned. During the simulation, we used the averaged flow rate for each order to predict the pressure drop and once the pressure drop is predicted, the flow rate is corrected to match the computed pressure drop for each vessel. The final results for 3 cardiac cycles is presented and compared to the clinical data.

Keywords: blood flow, morphometric data, vascular tree, Strahler ordering system

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Authors: Vandana Singh, Subash Singh

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Introduction: Oral squamous cell carcinoma is the most common malignant tumor of the oral cavity. Normally the death of cell and the growth are active processes and depend not only on external factors but also on the expression of genes like Bcl-2, which activate and inhibit apoptosis. The term Bcl-2 is an acronym for B-cell lymphoma/ leukemia -2 genes. Objectives: An attempt was made to evaluate Bcl-2 oncoprotein expression in patients with oral precancer and cancer and to assess possible correlation between Bcl-2 oncoprotein expression and clinicopathological features of oral precancer and cancer. Material and Methods: This is a selective prospective clinical and immunohistochemical study. Clinicopathological examination is correlated with immunohistochemical findings. The immunolocalization of Bcl-2 protein is performed using the labeled streptavidin biotin (LSAB) method. To visualize the reaction, 3, 3-diaminobenzidine (DAB) is used. Results: Bcl-2 expression was positive in 11 [36.66 %, low Bcl-2 expression 3 (10.00 %), moderate Bcl-2 expression 7 (23.33 %), and high Bcl-2 expression 1 (3.33 %)] oral cancer cases and in 14 [87.50 %, low expression 8 (50 %), moderate expression 6 (37.50 %)] precancer cases. Conclusion: On the basis of the results of our study we conclude that positive Bcl-2 expression may be an indicator of poor prognosis in oral cancer and precancer. Relevance: It has been reported that there is deregulation of Bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. It can be used for revealing progression of epithelial dysplasia to malignancy and as a prognostic marker in oral precancer and cancer.

Keywords: BcL-2, immunohistochemistry, oral cancer, oral precancer

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Authors: Jamal Almatawah, Hamad Matar, Abdulsalam Altemeemi

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The World Health Organization (WHO) has recognized environmental noise as harmful pollution that causes adverse psychosocial and physiologic effects on human health. The motor vehicle is considered to be one of the main source of noise pollution. It is a universal phenomenon, and it has grown to the point that it has become a major concern for both the public and policymakers. The aim of this paper, therefore, is to investigate the Traffic noise levels and the contributing factors that affect its level, such as traffic volume, heavy-vehicle Speed and other metrological factors in Ishbiliyah as a sample of a residential area in Kuwait. Three types of roads were selected in Ishbiliyah expressway, major arterial and collector street. The other source of noise that interferes the traffic noise has also been considered in this study. Traffic noise level is measured and analyzed using the Bruel & Kjaer outdoor sound level meter 2250-L (2250 Light). The Count-Cam2 Video Camera has been used to collect the peak and off-peak traffic count. Ambient Weather WM-5 Handheld Weather Station is used for metrological factors such as temperature, humidity and wind speed. Also, the spot speed was obtained using the radar speed: Decatur Genesis model GHD-KPH. All the measurement has been detected at the same time (simultaneously). The results showed that the traffic noise level is over the allowable limit on all types of roads. The average equivalent noise level (LAeq) for the Expressway, Major arterial and Collector Street was 74.3 dB(A), 70.47 dB(A) and 60.84 dB(A), respectively. In addition, a Positive Correlation coefficient between the traffic noise versus traffic volume and between traffic noise versus 85th percentile speed was obtained. However, there was no significant relation and Metrological factors. Abnormal vehicle noise due to poor maintenance or user-enhanced exhaust noise was found to be one of the highest factors that affected the overall traffic noise reading.

Keywords: traffic noise, residential area, pollution, vehicle noise

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Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

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In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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