Search results for: blood cancer

Authors: Shreyas S. Hegde, Anindya Deb, Suresh Nagesh

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Computational bio-mechanics is developing rapidly as a non-invasive tool to assist the medical fraternity to help in both diagnosis and prognosis of human body related issues such as injuries, cardio-vascular dysfunction, atherosclerotic plaque etc. Any system that would help either properly diagnose such problems or assist prognosis would be a boon to the doctors and medical society in general. Recently a lot of work is being focused in this direction which includes but not limited to various finite element analysis related to dental implants, skull injuries, orthopedic problems involving bones and joints etc. Such numerical solutions are helping medical practitioners to come up with alternate solutions for such problems and in most cases have also reduced the trauma on the patients. Some work also has been done in the area related to the use of computational fluid mechanics to understand the flow of blood through the human body, an area of hemodynamics. Since cardio-vascular diseases are one of the main causes of loss of human life, understanding of the blood flow with and without constraints (such as blockages), providing alternate methods of prognosis and further solutions to take care of issues related to blood flow would help save valuable life of such patients. This project is an attempt to use computational fluid dynamics (CFD) to solve specific problems related to hemodynamics. The hemodynamics simulation is used to gain a better understanding of functional, diagnostic and theoretical aspects of the blood flow. Due to the fact that many fundamental issues of the blood flow, like phenomena associated with pressure and viscous forces fields, are still not fully understood or entirely described through mathematical formulations the characterization of blood flow is still a challenging task. The computational modeling of the blood flow and mechanical interactions that strongly affect the blood flow patterns, based on medical data and imaging represent the most accurate analysis of the blood flow complex behavior. In this project the mathematical modeling of the blood flow in the arteries in the presence of successive blockages has been analyzed using CFD technique. Different cases of blockages in terms of percentages have been modeled using commercial software CATIA V5R20 and simulated using commercial software ANSYS 15.0 to study the effect of varying wall shear stress (WSS) values and also other parameters like the effect of increase in Reynolds number. The concept of fluid structure interaction (FSI) has been used to solve such problems. The model simulation results were validated using in vivo measurement data from existing literature

Keywords: computational fluid dynamics, hemodynamics, blood flow, results validation, arteries

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Authors: Rasha Ahmadi

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Glioblastoma is one of the most frequent brain malignancies, having a high mortality rate and limited survival in individuals with this malignancy. Despite different treatments and surgery, recurrence of glioblastoma cancer stem cells may arise as a subsequent tumor. For this reason, it is crucial to research the markers associated with glioblastoma stem cells and specifically their microenvironment. In this study, using bioinformatics analysis, we analyzed and nominated genes in the microenvironment pathways of glioblastoma stem cells. In this study, an appropriate database was selected for analysis by referring to the GEO database. This dataset comprised gene expression patterns in stem cells derived from glioblastoma patients. Gene clusters were divided as high and low expression. Enrichment databases such as Enrichr, STRING, and GEPIA were utilized to analyze the data appropriately. Finally, we extracted the potential genes 2700 high-expression and 1100 low-expression genes are implicated in the metabolic pathways of glioblastoma cancer progression. Cellular senescence, MAPK, TNF, hypoxia, zimosterol biosynthesis, and phosphatidylinositol metabolism pathways were substantially expressed and the metabolic pathways were downregulated. After assessing the association between protein networks, MSMP, SOX2, FGD4 ,and CNTNAP3 genes with high expression and DMKN and SBSN genes with low were selected. All of these genes were observed in the survival curve, with a survival of fewer than 10 percent over around 15 months. hsa-mir-192-5p, hsa-mir-129-5p, hsa-mir-215-5p, hsa-mir-335-5p, and hsa-mir-340-5p played key function in glioblastoma cancer stem cells microenviroments. We introduced critical genes through integrated and regular bioinformatics studies by assessing the amount of gene expression profile data that can play an important role in targeting genes involved in the energy and microenvironment of glioblastoma cancer stem cells. Have. This study indicated that hsa-mir-192-5p, and hsa-mir-129-5p are appropriate candidates for this.

Keywords: Glioblastoma, Cancer Stem Cells, Biomarker Discovery, Gene Expression Profiles, Bioinformatics Analysis, Tumor Microenvironment

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Authors: Ammaarah Gamieldien

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Depression is a very common and serious mental illness that has a significant impact on both the social and economic aspects of sufferers worldwide. This study aimed to investigate the association between body mass index (BMI), blood pressure, and lipid profiles with mental health symptoms in university students. Secondary objectives included the associations between the variables (BMI, blood pressure, and lipids) with themselves, as they are key factors in cardiometabolic disease. Sixty-three (63) students participated in the study. Thirty-two (32) were assigned to the control group (minimal-mild depressive symptoms), while 31 were assigned to the depressive group (moderate to severe depressive symptoms). Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) were used to assess depressive scores. Anthropometric measurements such as weight (kg), height (m), waist circumference (WC), and hip circumference were measured. Body mass index (BMI) and ratios such as waist-to-hip ratio (WHR) and waist-to-height ratio (WtHR) were also calculated. Blood pressure was measured using an automated AfriMedics blood pressure machine, while lipids were measured using a CardioChek plus analyzer machine. Statistics were analyzed via the SPSS statistics program. There were no significant associations between anthropometric measurements and depressive scores (p > 0.05). There were no significant correlations between lipid profiles and depression when running a Spearman’s rho correlation (P > 0.05). However, total cholesterol and LDL-C were negatively associated with depression, and triglycerides were positively associated with depression after running a point-biserial correlation (P < 0.05). Overall, there were no significant associations between blood pressure measurements and depression (P > 0.05). However, there was a significant moderate positive correlation between systolic blood pressure and MADRS scores in males (P < 0.05). Depressive scores positively and strongly correlated to how long it takes participants to fall asleep. There were also significant associations with regard to the secondary objectives. This study indicates the importance of determining the prevalence of depression among university students in South Africa. If the prevalence and factors associated with depression are addressed, depressive symptoms in university students may be improved.

Keywords: depression, blood pressure, body mass index, lipid profiles, mental health symptoms

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Authors: Hae-Yeoun Lee

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Quantification of cardiac function is performed by calculating blood volume and ejection fraction in routine clinical practice. However, these works have been performed by manual contouring,which requires computational costs and varies on the observer. In this paper, an automatic left ventricle segmentation algorithm on cardiac magnetic resonance images (MRI) is presented. Using knowledge on cardiac MRI, a K-mean clustering technique is applied to segment blood region on a coil-sensitivity corrected image. Then, a graph searching technique is used to correct segmentation errors from coil distortion and noises. Finally, blood volume and ejection fraction are calculated. Using cardiac MRI from 15 subjects, the presented algorithm is tested and compared with manual contouring by experts to show outstanding performance.

Keywords: cardiac MRI, graph searching, left ventricle segmentation, K-means clustering

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Authors: Elshymaa A. Abdelnaby, Amal M. Abo El-Maaty

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This study aimed to investigate dynamics of dominant and subordinate follicles change in dimensions, vascularity and angiogenic hormones after completing deviation till ovulation. Five cyclic mares were subjected to daily blood sampling and rectal Doppler ultrasonographic examination along two estrous cycles. Using electronic calipers, three diameters were recorded for each follicle to estimate area and volume. Leptin, Insulin-like growth factor-I (IGF-1), nitric oxide (NO) and estradiol (E2) were measured. Area of color- and power- Doppler modes with area and circumference of the first (preovulatory) and subordinate follicles were measured in pixels. Follicles were classified into F1O (preovulatory), F2O (subordinate), F3O (third ovulatory) on the dominant ovary and F1C (first contra) and F2C (second contra) on the contralateral ovary. Days before ovulation significantly (P < 0.0001) affected diameter, circumference, area, volume, area/pixel and antrum area of the preovulatory follicle. With the increase of diameter, area, volume area/pixel, antrum area/pixel and circumference of F1O, those of all subordinates were decreasing. The blue blood flow area, power and power minus red blood flow area of F1O increased from day -6 till day of ovulation (day 0), but red blood flow area significantly decreased. F1O had the lowest percent of colored pixels and percent of the colored pixels without antrum. Estradiol and leptin increased from day -6 till day 0 but IGF-1 decreased till day -1 but NO achieved a peak on day -3 then decreased till day 0. In conclusion, antrum growth, blood flow and angiogenic hormones play a role in maturation and ovulation of the dominant follicle in mares.

Keywords: angiogenic hormones, blood flow, mare, preovulatory follicle

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Authors: A. Dean, M. Pitcher, L. Storer, K. Shanahan, I. Rio, B. Mann

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Purpose: Breast cancer survivors are at risk of specific physical and psycho-social issues, such as arm swelling, fatigue, and depression. Firstly, we investigate symptoms reported by Australia breast cancer survivors upon completion of definitive treatment. Secondly, we evaluate the appropriateness and effectiveness of a multi-centre pilot program nurse-led clinic to identify these issues and make timely referrals to available services. Methods: Patients post-definitive treatment (excluding ongoing hormonal therapy) for early breast cancer or ductal carcinoma in situ were invited to participate. An hour long appointment with a breast care nurse (BCN) was scheduled. In preparation, patients completed validated quality-of-life surveys (FACT-B, Menopause Rating Scale, Distress Thermometer). During the appointment, issues identified in the surveys were addressed and referrals to appropriate services arranged. Results: 183 of 274 (67%) eligible patients attended a nurse-led clinic. Mean age 56.8 years (range 29-87 years), 181/183 women, 105/183 post-menopausal. 96 (55%) participants reported significant level of distress; 31 (18%) participants reported extreme distress or depression. Distress stemmed from a lack of energy (56/175); poor quality of sleep (50/176); inability to work or participate in household activities (35/172) and problems with sex life (28/89). 166 referrals were offered; 94% of patients accepted the referrals. 65% responded to a follow-up survey: the majority of women either strongly agreed or agreed that the BCN was overwhelmingly supportive, helpful in making referrals, and compassionate towards them. 39% reported making lifestyle changes as a result of the BCN. Conclusion: Breast cancer survivors experience a unique set of challenges, including low mood, difficulty sleeping, problems with sex life and fear of disease recurrence. The nurse-led clinic model is an appropriate and effective method to ensure physical and psycho-social issues are identified and managed in a timely manner. This model empowers breast cancer survivors with information about their diagnosis and available services.

Keywords: early breast cancer, survivorship, breast care nursing, oncology nursing and cancer care

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Authors: Prabhavathi Sundaram, Heidi Abrahamse

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In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

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Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid

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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.

Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk

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Authors: Ching-Yi Yiu, Hui-Chen Hsu

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Objectives: Head and neck cancer (HNC) is a big global health problem in the world. Despite the development of diagnosis and treatment, the overall survival of HNC is still low. The well recognition of the interaction of the host immune system and cancer cells has led to realizing the processes of tumor initiation, progression and metastasis. Many systemic inflammatory responses have been shown to play a crucial role in cancer progression. The pre and post-treatment nutritional and immunological status of HNC patients is a reliable prognostic indicator of tumor outcomes and survivors. Methods: Between July 2020 to June 2022, We have enrolled 60 HNC patients, including 59 males and 1 female, in Chi Mei Medical Center, Liouying, Taiwan. The age distribution was from 37 to 81 years old (y/o), with a mean age of 57.6 y/o. We evaluated the pre-and post-treatment nutritional and immunological status of these HNC patients with body weight, body weight loss, body mass index (BMI), whole blood count including hemoglobin (Hb), lymphocyte, neutrophil and platelet counts, biochemistry including prealbumin, albumin, c-reactive protein (CRP), with the time period of before treatment, post-treatment 3 and 6 months. We calculated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) to assess how these biomarkers influence the outcomes of HNC patients. Results: We have carcinoma of the hypopharynx in 21 cases with 35％, carcinoma of the larynx in 9 cases, carcinoma of the tonsil and tongue every 6 cases, carcinoma soft palate and tongue base every 5 cases, carcinoma of buccal mucosa, retromolar trigone and mouth floor every 2 cases, carcinoma of the hard palate and low lip each 1 case. There were stage I 15 cases, stage II 13 cases, stage III 6 cases, stage IVA 10 cases, and stage IVB 16 cases. All patients have received surgery, chemoradiation therapy or combined therapy. We have wound infection in 6 cases, 2 cases of pharyngocutaneous fistula, flap necrosis in 2 cases, and mortality in 6 cases. In the wound infection group, the average BMI is 20.4 kg/m2; the average Hb is 12.9 g/dL, the average albumin is 3.5 g/dL, the average NLR is 6.78, and the average PLR is 243.5. In the PC fistula and flap necrosis group, the average BMI is 21.65 kg/m2; the average Hb is 11.7 g/dL, the average albumin is 3.15 g/dL, average NLR is 13.28, average PLR is 418.84. In the mortality group, the average BMI is 22.3 kg/m2; the average Hb is 13.58 g/dL, the average albumin is 3.77 g/dL, the average NLR is 6.06, and the average PLR is 275.5. Conclusion: HNC is a big challenging public health problem worldwide, especially in the high prevalence of betel nut consumption area Taiwan. Besides the definite risk factors of smoking, drinking and betel nut related, the other biomarkers may play significant prognosticators in the HNC outcomes. We concluded that the average BMI is less than 22 kg/m2, the average Hb is low than 12.0 g/dL, the average albumin is low than 3.3 g/dL, the average NLR is low than 3, and the average PLR is more than 170, the surgical complications and mortality will be increased, and the prognosis is poor in HNC patients.

Keywords: nutritional, immunological, neutrophil-to-lymphocyte ratio, paltelet-to-lymphocyte ratio.

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Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

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Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: Khadija Al-Hosni, Moon Fai Chan, Mohammed Al-Azri

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Background: Several studies suggest that most school-age adolescents are poorly informed on cancer warning signs and risk factors. Providing adolescents with sufficient knowledge would increase their awareness in adulthood and improve seeking behaviors later. Significant: The results will provide a clear vision in assisting key decision-makers in formulating policies on the students' awareness programs towards cancer. So, the likelihood of avoiding cancer in the future will be increased or even promote early diagnosis. Objectives: to evaluate the effectiveness of an education program designed to increase awareness of cancer signs and symptoms risk factors, improve the behavior of seeking help among school students in Oman, and address the barriers to obtaining medical help. Methods: A randomized controlled trial with two groups was conducted in Oman. A total of 1716 students (n=886/control, n= 830/education), aged 15-17 years, at 10th and 11th grade from 12 governmental schools 3 in governorates from 20-February-2022 to 12-May-2022. Basic demographic data were collected, and the Cancer Awareness Measure (CAM) was used as the primary outcome. Data were collected at baseline (T0) and 4 weeks after (T1). The intervention group received an education program about cancer's cause and its signs and symptoms. In contrast, the control group did not receive any education related to this issue during the study period. Non-parametric tests were used to compare the outcomes between groups. Results: At T0, the lamp was the most recognized cancer warning sign in the control (55.0%) and intervention (55.2%) groups. However, there were no significant changes at T1 for all signs in the control group. In contrast, all sign outcomes were improved significantly (p<0.001) in the intervention group, and the highest response was unexplained pain (93.3%). Smoking was the most recognized risk factor in both groups: (82.8% for control; 84.1% for intervention) at T0. However, there was no significant change in T1 for the control group, but there was for the intervention group (p<0.001), the highest identification was smoking cigarettes (96.5%). Too scared was the largest barrier to seeking medical help by students in the control group at T0 (63.0%) and T1 (62.8%). However, there were no significant changes in all barriers in this group. Otherwise, being too embarrassed (60.2%) was the largest barrier to seeking medical help for students in the intervention group at T0 and too scared (58.6%) at T1. Although there were reductions in all barriers, significant differences were found in six of ten only (p<0.001). Conclusion: The intervention was effective in improving students' awareness of cancer symptoms, warning signs (p<0.001), and risk factors (p<0.001 reduced the most addressed barriers to seeking medical help (p<0.001) in comparison to the control group. The Ministry of Education in Oman could integrate awareness of cancer within the curriculum, and more interventions are needed on the sociological part to overcome the barriers that interfere with seeking medical help.

Keywords: adolescents, awareness, cancer, education, intervention, student

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Authors: Xi Gu, Guan Heng Yeoh, Victoria Timchenko

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In the current work, a three-dimensional geometry of a 75% stenosed blood vessel is analysed. Large eddy simulation (LES) with the help of a dynamic subgrid scale Smagorinsky model is applied to model the turbulent pulsatile flow. The geometry, the transmural pressure and the properties of the blood and the elastic boundary were based on clinical measurement data. For the flexible wall model, a thin solid region is constructed around the 75% stenosed blood vessel. The deformation of this solid region was modelled as a deforming boundary to reduce the computational cost of the solid model. Fluid-structure interaction is realised via a two-way coupling between the blood flow modelled via LES and the deforming vessel. The information of the flow pressure and the wall motion was exchanged continually during the cycle by an arbitrary lagrangian-eulerian method. The boundary condition of current time step depended on previous solutions. The fluctuation of the velocity in the post-stenotic region was analysed in the study. The axial velocity at normalised position Z=0.5 shows a negative value near the vessel wall. The displacement of the elastic boundary was concerned in this study. In particular, the wall displacement at the systole and the diastole were compared. The negative displacement at the stenosis indicates a collapse at the maximum velocity and the deceleration phase.

Keywords: Large Eddy Simulation, Fluid Structural Interaction, constricted artery, Computational Fluid Dynamics

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Authors: Chien-Lin Wang, Cha-Ling Ko, Tainsong Chen

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Pulse Blood pressure (BP) is one of the vital signs, and is an index that helps determining the stability of life. In this respect, some spinal cord injury patients need to take the tilt table test. While doing the test, the posture changes abruptly, and may cause a patient’s BP to change abnormally. This may cause patients to feel discomfort, and even feel as though their life is threatened. Therefore, if a continuous non-invasive BP assessment system were built, it could help to alert health care professionals in the process of rehabilitation when the BP value is out of range. In our research, BP assessed by the pulse transit time technique was developed. In the system, we use a self-made photoplethysmograph (PPG) sensor and filter circuit to detect two PPG signals and to calculate the time difference. The BP can immediately be assessed by the trend line. According to the results of this study, the relationship between the systolic BP and PTT has a highly negative linear correlation (R2=0.8). Further, we used the trend line to assess the value of the BP and compared it to a commercial sphygmomanometer (Omron MX3); the error rate of the system was found to be in the range of ±10%, which is within the permissible error range of a commercial sphygmomanometer. The continue blood pressure measurement from pulse transit time technique may have potential to become a convenience method for clinical rehabilitation.

Keywords: continous blood pressure measurement, PPG, time transit time, transit velocity

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Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

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Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma

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Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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Authors: Arina V. Tankanag, Gennady V. Krasnikov, Nikolai K. Chemeris

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The development of respiration-dependent oscillations in the peripheral blood flow may occur by at least two mechanisms. The first mechanism is related to the change of venous pressure due to mechanical activity of lungs. This phenomenon is known as ‘respiratory pump’ and is one of the mechanisms of venous return of blood from the peripheral vessels to the heart. The second mechanism is related to the vasomotor reflexes controlled by the respiratory modulation of the activity of centers of the vegetative nervous system. Early high phase synchronization of respiration-dependent blood flow oscillations of left and right forearm skin in healthy volunteers at rest was shown. The aim of the work was to study the effect of deep controlled breathing on the phase synchronization of skin blood flow oscillations. 29 normotensive non-smoking young women (18-25 years old) of the normal constitution without diagnosed pathologies of skin, cardiovascular and respiratory systems participated in the study. For each of the participants six recording sessions were carried out: first, at the spontaneous breathing rate; and the next five, in the regimes of controlled breathing with fixed breathing depth and different rates of enforced breathing regime. The following rates of controlled breathing regime were used: 0.25, 0.16, 0.10, 0.07 and 0.05 Hz. The breathing depth amounted to 40% of the maximal chest excursion. Blood perfusion was registered by laser flowmeter LAKK-02 (LAZMA, Russia) with two identical channels (wavelength 0.63 µm; emission power, 0.5 mW). The first probe was fastened to the palmar surface of the distal phalanx of left forefinger; the second probe was attached to the external surface of the left forearm near the wrist joint. These skin zones were chosen as zones with different dominant mechanisms of vascular tonus regulation. The degree of phase synchronization of the registered signals was estimated from the value of the wavelet phase coherence. The duration of all recording was 5 min. The sampling frequency of the signals was 16 Hz. The increasing of synchronization of the respiratory-dependent skin blood flow oscillations for all controlled breathing regimes was obtained. Since the formation of respiration-dependent oscillations in the peripheral blood flow is mainly caused by the respiratory modulation of system blood pressure, the observed effects are most likely dependent on the breathing depth. It should be noted that with spontaneous breathing depth does not exceed 15% of the maximal chest excursion, while in the present study the breathing depth was 40%. Therefore it has been suggested that the observed significant increase of the phase synchronization of blood flow oscillations in our conditions is primarily due to an increase of breathing depth. This is due to the enhancement of both potential mechanisms of respiratory oscillation generation: venous pressure and sympathetic modulation of vascular tone.

Keywords: deep controlled breathing, peripheral blood flow oscillations, phase synchronization, wavelet phase coherence

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Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

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Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

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Authors: Mashitoh Abd Rahman, Najihah Mohd Hashim, Faiqah Ramli, Syam Mohan, Noraziah Nordin, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Ovarian cancer is the most lethal gynecological malignancies. HME5, a prenylflavanoid has been isolated from local medicinal plant. This compound has been reported to possess a broad spectrum of biological activities including anticancer property. However, the potential of HME5 as an antiproliferative and cytotoxic agent on an ovarian cancer cells has not yet been investigated. In this present study, we examined the antiproliferative and cytotoxic effect of HME5 on Caov-3 (Human Ovarian Adenocarcinoma) cell line by using 3-[4,5-dimethylthizol-2-y]-2,5-diphenyltetrazolium bromide (MTT) assay, Acridine orange and propidium Iodide (AOPi) and cell cycle analysis study. HME5 has shown to inhibit Caov-3 in a time-dependent manner with the IC50 values of 5µg/ml, 2µg/ml and 1µg/ml after 24h, 48h and 72h treatment, respectively. Morphological study from AOPi analysis showed that HME5 induced apoptosis after 24 and 48h post-treatment. Nevertheless, HME5 exhibited cell cycle arrest at G1 phase as indicated in flow cytometry cell cycle profiling. In conclusion, HME5 inhibited proliferation of Caov-3 through induction of apoptosis and cell cycle arrest at G1 phase.

Keywords: apoptosis, prenylflavanoid, ovarian cancer, HME5

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Authors: Linda P. M. Pluymen, Mariska M. G. Leeflang, I. Stegeman, Henock G. Yebyo, Anne E. M. Brabers, Patrick M. Bossuyt, E. Dekker, Anke J. Woudstra, Mirjam P. Fransen

Abstract:

Weighing the benefits and harms of colorectal cancer screening can be difficult for individuals. An existing online decision aid was expanded with a benefit-harm analysis to help people make an informed decision about participating in colorectal cancer screening. In a randomized controlled trial, we investigated whether those in the intervention group who used the decision aid with benefit-harm analysis were more certain about their decision than those in the control group who used the decision aid without benefit-harm analysis. Participants were 623 (39% of those invited) men and women aged 45 until 75 years old. Analyses were performed in those 386 participants (62%) who reported to have completed the entire decision aid. No statistically significant differences were observed between intervention and control group in decisional conflict score (mean difference 2.4, 95% CI -0.9, 5.6), clarity of values (mean difference 1.0, 95% CI -4.4, 6.6), deliberation score (mean difference 0.5, 95% CI -0.6, 1.7), anxiety score (mean difference 0.0, 95% CI -0.3, 0.3) and risk perception score (mean difference 0.1, -0.1, 0.3). Adding a benefit-harm analysis to an online decision aid did not improve informed decision making about participating in colorectal cancer screening.

Keywords: benefit-harm analysis, decision aid, informed decision making, personalized decision making

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Authors: R. Tudugala, B. M. A. I. Balasooriya, W. M. Ediri Arachchi, R. W. M. W. K. Rathnayake, T. D. Premaratna

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Brachytherapy involves placing a source of radiation near the cancer site which gives promising prognosis for cervical cancer treatments. The purpose of this study was to evaluate the effect of random variation of treated volumes in between fractions in the 2D image based fractionated high dose rate brachytherapy for cervical cancer at National Cancer Institute Maharagama, Sri Lanka. Dose plans were analyzed for 150 cervical cancer patients with orthogonal radiographs (2D) based brachytherapy. ICRU treated volumes was modeled by translating the applicators with the help of “Multisource HDR plus software”. The difference of treated volumes with respect to the applicator geometry was analyzed by using SPSS 18 software; to derived patient population based estimates of delivered treated volumes relative to ideally treated volumes. Packing was evaluated according to bladder dose, rectum dose and geometry of the dose distribution by three consultant radiation oncologist. The difference of treated volumes depends on types of the applicators, which was used in fractionated brachytherapy. The means of the “Difference of Treated Volume” (DTV) for “Evenly activated tandem (ET)” length” group was ((X_1)) -0.48 cm3 and ((X_2)) 11.85 cm3 for “Unevenly activated tandem length (UET) group. The range of the DTV for ET group was 35.80 cm3 whereas UET group 104.80 cm3. One sample T test was performed to compare the DTV with “Ideal treatment volume difference (0.00cm3)”. It is evident that P value was 0.732 for ET group and for UET it was 0.00 moreover independent two sample T test was performed to compare ET and UET groups and calculated P value was 0.005. Packing was evaluated under three categories 59.38% used “Convenient Packing Technique”, 33.33% used “Fairly Packing Technique” and 7.29% used “Not Convenient Packing” in their fractionated brachytherapy treatments. Random variation of treated volume in ET group is much lower than UET group and there is a significant difference (p<0.05) in between ET and UET groups which affects the dose distribution of the treatment. Furthermore, it can be concluded nearly 92.71% patient’s packing were used acceptable packing technique at NCIM, Sri Lanka.

Keywords: brachytherapy, cervical cancer, high dose rate, tandem, treated volumes

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Authors: Rahy Farooq, Maria Ahmad Khan, Ayesha Isani Majeed

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Objective: The main aim of this research is to assess the knowledge, attitude and practices of female nursing staff and nursing students regarding breast cancer, to provide a baseline for monitoring trends of breast cancer awareness in them. Background: Healthcare professionals are a direct source of information for the patients and the general public as a whole. It is, therefore, essential that the information they convey be accurate and helps in building additional awareness. However, clinical experience does not influence the knowledge, attitude and practices regarding breast cancer. Nurses, being the prime part of the healthcare professionals, play a significant role and hence, their awareness regarding this pressing issue is pertinent. Lack of awareness regarding common presenting symptoms or breast cancer risk factors translates to poor breast cancer screening practices and late diagnosis. Methodology: A cross-sectional study of 280 female nurses was conducted at a tertiary care hospital in Islamabad, Pakistan. A pre-tested structured questionnaire with additional variables like cultural barriers to seeking medical help was used. The scores for outcome variables including knowledge, attitude and practices were pre-defined. Data was analyzed using SPSSv23. Results: Of the 280 participants with a mean age of 28.99±9.98 years, 142 (50.7%) were married, and 138 (49.3%) were unmarried. Mean scores were computed to be 6.14±2.93 (out of 12), 0.30±0.7 (out of 3) and 9.53±1.92 (out of 16) for knowledge, attitude and practice respectively. Using independent sample T-test, a statistically significant correlation was found when means for the score of Attitude was compared with age. With a p-value of 0.018, 117 nurses of age more than 30 years, faced more practical, financial, emotional and service barriers as compared to 163 women younger than 30 years of age. Knowledge of age-related lifetime risks was also significantly poor more in single women; with a p-value of 0.006 for identification of correct age as a risk factor and a p-value of 0.005 for correct identification of risk for development of breast cancer in the lifetime of women. By application of Chi-square test, there was a significant correlation between marital status and cultural barriers to seeking medical help, showing that single women (58.7%) shy away from talking about breast cancer considering it a taboo (p-value 0.028) whereas, more married nurses (59.2%) were apprehensive that they might be considered at fault by the society, as compared to 40.8% of single nurses. (p-value 0.038). Conclusion: Owing to the scarcity of awareness among nurses, this study recognizes the need for delivering effective information to the female nurses regarding breast cancer. Educating patients is likely to be effective if the female nurses play their part and have correct attitudes towards breast cancer practices. A better understanding of the knowledge and practices regarding breast cancer among the nursing population will enable high-risk patients to be recognized early. Therefore, we recommend arrangement of special courses and seminars for all healthcare professionals including the nursing staff.

Keywords: breast cancer, cultural barriers, kap, nurses

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Authors: Liane J. Ioannou, Jonathan Serpell, Joanne Dean, Cino Bendinelli, Jenny Gough, Dean Lisewski, Julie Miller, Win Meyer-Rochow, Stan Sidhu, Duncan Topliss, David Walters, John Zalcberg, Susannah Ahern

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Background: The occurrence of thyroid cancer is increasing throughout the developed world, including Australia and New Zealand, and since the 1990s has become the fastest increasing malignancy. Following the success of a number of institutional databases that monitor outcomes after thyroid surgery, the Australian and New Zealand Endocrine Surgeons (ANZES) agreed to auspice the development of a bi-national thyroid cancer registry. Objectives: To establish a bi-national population-based clinical quality registry with the aim of monitoring and improving the quality of care provided to patients diagnosed with thyroid cancer in Australia and New Zealand. Patients and Methods: The Australian and New Zealand Thyroid Cancer Registry (ANZTCR) captures clinical data for all patients, over the age of 18 years, diagnosed with thyroid cancer, confirmed by histopathology report, that have been diagnosed, assessed or treated at a contributing hospital. Data is collected by endocrine surgeons using a web-based interface, REDCap, primarily via direct data entry. Results: A multi-disciplinary Steering Committee was formed, and with operational support from Monash University the ANZTCR was established in early 2017. The pilot phase of the registry is currently operating in Victoria, New South Wales, Queensland, Western Australia and South Australia, with over 30 sites expected to come on board across Australia and New Zealand in 2018. A modified-Delphi process was undertaken to determine the key quality indicators to be reported by the registry, and a minimum dataset was developed comprising information regarding thyroid cancer diagnosis, pathology, surgery, and 30-day follow up. Conclusion: There are very few established thyroid cancer registries internationally, yet clinical quality registries have shown valuable outcomes and patient benefits in other cancers. The establishment of the ANZTCR provides the opportunity for Australia and New Zealand to further understand the current practice in the treatment of thyroid cancer and reasons for variation in outcomes. The engagement of endocrine surgeons in supporting this initiative is crucial. While the pilot registry has a focus on early clinical outcomes, it is anticipated that future collection of longer-term outcome data particularly for patients with the poor prognostic disease will add significant further value to the registry.

Keywords: thyroid cancer, clinical registry, population health, quality improvement

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Authors: Olukayode Bamgbose, Feyisola Agboola, Adewale M. Taiwo, Olanrewaju Olujimi Oluwole Terebo, Azeez Soyingbe, Akeem Bamgbade

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The present study evaluated the contents and health risk assessment of metals determined in milk and milk product samples collected from the Abeokuta market. Forty-five milk and milk product (yoghurt) samples were digested and analysed for selected metals using Atomic Absorption Spectrophotometric method. Health risk assessment was evaluated for hazard quotient (HQ), hazard index (HI), and cancer risk (CR). Data were subjected to descriptive and inferential statistics. The concentrations of Zn, which ranged from 3.24±0.59 to 4.35±0.59 mg/kg, were the highest in the samples. Cr and Cd were measured below the detection limit of the analytical instrument, while the Pb level was higher than the Codex Alimentarius Commission value of 0.02 mg/kg, indicating unsafe for consumption. However, the HQ of Pb and other metals in milk and milk product samples was less than 1.0, thereby establishing no adverse health effects for Pb and other metals. The distribution pattern of metals in milk and milk product samples followed the decreasing order of Zn > Fe > Ni > Co > Cu > Mn > Pb > Cd/Cr. The CR levels of meals were also less than the permissible limit of 1.0 x 10-4, establishing no possible development of cancer. Keywords: adverse effects, cancer, metals, milk, milk product, the permissible limit.

Keywords: adverse effects, cancer, metals, milk, milk product, permissible limit

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Authors: Aileen F. Wang

Abstract:

Mammography has been one of the most reliable methods for early detection and diagnosis of breast cancer. However, mammography misses about 17% and up to 30% of breast cancers due to the subtle and unstable appearances of breast cancer in their early stages. Recent computer-aided diagnosis (CADx) technology using Zernike moments has improved detection accuracy. However, it has several drawbacks: it uses manual segmentation, Zernike moments are not robust, and it still has a relatively high false negative rate (FNR)–17.6%. This project will focus on the development of a novel breast cancer detection algorithm to automatically segment the breast mass and further reduce FNR. The algorithm consists of automatic segmentation of a single breast mass using Point Region Growing Segmentation, reconstruction of the segmented breast mass using Pseudo-Zernike moments, and classification of the breast mass using the root mean square (RMS). A comparative study among the various algorithms on the segmentation and reconstruction of breast masses was performed on randomly selected mammographic images. The results demonstrated that the newly developed algorithm is the best in terms of accuracy and cost effectiveness. More importantly, the new classifier RMS has the lowest FNR–6%.

Keywords: computer aided diagnosis, mammography, point region growing segmentation, pseudo-zernike moments, root mean square

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Authors: Nura Lawal, Lawal Suleiman Bilbis, Rabiu Aliyu Umar, Anas A. Sabir

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Metabolic syndrome (MS) a high-risk condition involving obesity, dyslipidemia, hypertension, and diabetes mellitus is prevalent in Nigeria. The study aims to formulate an antioxidant-rich nutraceutical from locally available foodstuff (onion, garlic, ginger, tomato, lemon, palm oil, watermelon seeds) and investigate their effects on blood pressure, body weight, serum glucose, lipid profile, insulin and oxidative stress markers in salt-induced rats. The rats were placed on 8% salt diet for 6 weeks and then supplementation and treatment with nutraceutical and nifedipine in the presence of salt diet for additional 4 weeks. Feeding rats with salt diet for 6 weeks increased blood pressure and body weight of the salt-loaded rats relative to control. Significant (P < 0.001) increase in serum blood glucose and lipid profile, and the decrease in high-density lipoprotein-cholesterol (HDL-C) was observed in salt-loaded rats as compared with control. Both supplementation and treatment (nifedipine) lowered the blood pressure but the only supplementation lowered the body weight. Supplementation with nutraceutical resulted in significant (P < 0.001) decrease in the serum blood glucose, lipid profile, malonyldialdehyde (MDA), insulin levels, insulin resistance, and increased HDL-C and antioxidant indices. The percentage protection against atherogenesis was 76.5±2.13%. There is strong positive correlation between blood pressure, body weight and serum blood glucose, lipid profile, markers of oxidative stress and strong negative correlation with HDL-C and antioxidant status. The results suggest that the nutraceuticals are useful in reversing most of the component of metabolic syndrome and might be beneficial in the treatment of patients with metabolic syndrome.

Keywords: metabolic syndrome, hypertension, diabetes mallitus, obesity

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Authors: Mehdi Behbahani, Sebastian Rible, Charles Moulinec, Yvan Fournier, Mike Nicolai, Paolo Crosetto

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Computational Fluid Dynamics blood-flow simulations are increasingly used to develop and validate blood-contacting medical devices. This study shows that numerical simulations can provide additional and accurate estimates of relevant hemodynamic indicators (e.g., recirculation zones or wall shear stresses), which may be difficult and expensive to obtain from in-vivo or in-vitro experiments. The most recent FDA (Food and Drug Administration) benchmark consisted of a simplified centrifugal blood pump model that contains fluid flow features as they are commonly found in these devices with a clear focus on highly turbulent phenomena. The FDA centrifugal blood pump study is composed of six test cases with different volumetric flow rates ranging from 2.5 to 7.0 liters per minute, pump speeds, and Reynolds numbers ranging from 210,000 to 293,000. Within the frame of this study different turbulence models were tested including RANS models, e.g. k-omega, k-epsilon and a Reynolds Stress Model (RSM) and, LES. The partitioners Hilbert, METIS, ParMETIS and SCOTCH were used to create an unstructured mesh of 76 million elements and compared in their efficiency. Computations were performed on the JUQUEEN BG/Q architecture applying the highly parallel flow solver Code SATURNE and typically using 32768 or more processors in parallel. Visualisations were performed by means of PARAVIEW. Different turbulence models including all six flow situations could be successfully analysed and validated against analytical considerations and from comparison to other data-bases. It showed that an RSM represents an appropriate choice with respect to modeling high-Reynolds number flow cases. Especially, the Rij-SSG (Speziale, Sarkar, Gatzki) variant turned out to be a good approach. Visualisation of complex flow features could be obtained and the flow situation inside the pump could be characterized.

Keywords: blood flow, centrifugal blood pump, high performance computing, scalability, turbulence

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Authors: Fahimeh Palizban, Farshad Noravesh, Amir Hossein Saeidian, Mahya Mehrmohamadi

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In the recent decade, the emergence of liquid biopsy has significantly improved cancer monitoring and detection. Dying cells, including those originating from tumors, shed their DNA into the blood and contribute to a pool of circulating fragments called cell-free DNA. Accordingly, identifying the tissue origin of these DNA fragments from the plasma can result in more accurate and fast disease diagnosis and precise treatment protocols. Open chromatin regions are important epigenetic features of DNA that reflect cell types of origin. Profiling these features by DNase-seq, ATAC-seq, and histone ChIP-seq provides insights into tissue-specific and disease-specific regulatory mechanisms. There have been several studies in the area of cancer liquid biopsy that integrate distinct genomic and epigenomic features for early cancer detection along with tissue of origin detection. However, multimodal analysis requires several types of experiments to cover the genomic and epigenomic aspects of a single sample, which will lead to a huge amount of cost and time. To overcome these limitations, the idea of predicting OCRs from WGS is of particular importance. In this regard, we proposed a computational approach to target the prediction of open chromatin regions as an important epigenetic feature from cell-free DNA whole genome sequence data. To fulfill this objective, local sequencing depth will be fed to our proposed algorithm and the prediction of the most probable open chromatin regions from whole genome sequencing data can be carried out. Our method integrates the signal processing method with sequencing depth data and includes count normalization, Discrete Fourie Transform conversion, graph construction, graph cut optimization by linear programming, and clustering. To validate the proposed method, we compared the output of the clustering (open chromatin region+, open chromatin region-) with previously validated open chromatin regions related to human blood samples of the ATAC-DB database. The percentage of overlap between predicted open chromatin regions and the experimentally validated regions obtained by ATAC-seq in ATAC-DB is greater than 67%, which indicates meaningful prediction. As it is evident, OCRs are mostly located in the transcription start sites (TSS) of the genes. In this regard, we compared the concordance between the predicted OCRs and the human genes TSS regions obtained from refTSS and it showed proper accordance around 52.04% and ~78% with all and the housekeeping genes, respectively. Accurately detecting open chromatin regions from plasma cell-free DNA-seq data is a very challenging computational problem due to the existence of several confounding factors, such as technical and biological variations. Although this approach is in its infancy, there has already been an attempt to apply it, which leads to a tool named OCRDetector with some restrictions like the need for highly depth cfDNA WGS data, prior information about OCRs distribution, and considering multiple features. However, we implemented a graph signal clustering based on a single depth feature in an unsupervised learning manner that resulted in faster performance and decent accuracy. Overall, we tried to investigate the epigenomic pattern of a cell-free DNA sample from a new computational perspective that can be used along with other tools to investigate genetic and epigenetic aspects of a single whole genome sequencing data for efficient liquid biopsy-related analysis.

Keywords: open chromatin regions, cancer, cell-free DNA, epigenomics, graph signal processing, correlation clustering

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Authors: Nougrara Zineb

Abstract:

The unique structure of the blood vessels in the retina has been used for biometric identification. The retina blood vessel pattern is a unique pattern in each individual and it is almost impossible to forge that pattern in a false individual. The retina biometrics’ advantages include high distinctiveness, universality, and stability overtime of the blood vessel pattern. Once the creases have been extracted from the images, a registration stage is necessary, since the position of the retinal vessel structure could change between acquisitions due to the movements of the eye. Image registration consists of following steps: Feature detection, feature matching, transform model estimation and image resembling and transformation. In this paper, we present an algorithm of registration; it is based on the characterization of retinal feature points. For experiments, retinal images from the DRIVE database have been tested. The proposed methodology achieves good results for registration in general.

Keywords: fovea, optic disc, registration, retinal images

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Authors: Imene Soufli, Abdelkrim Hablal, Manel Amri, Moussa Labsi, Rania Sihem Boussa, Nassim Sid Idris, Chafia Touil-Boukoffa

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Crohn’s Disease (CD) is a relapsing–remitting inflammatory bowel disease with a progressive course. The aim of our study was to evaluate the relationship between the immunomarkers: Nitric Oxide (NO), pro-inflammatory cytokines, and blood count-based ratios and the outcome of corticosteroid or anti-TNF-α therapy in patients with complicated Crohn’s Disease. In this context, we evaluated the NLR as the ratio of neutrophil count to lymphocyte count, PLR as the ratio of platelet counts to lymphocyte count, and MLR as the ratio of monocyte count to lymphocyte count in patients and controls. Furthermore, we assessed NO production by the Griess method in plasma along with iNOS and NF-κB expression by immunofluorescence method in intestinal tissues of patients and controls. In the same way, we evaluated plasma TNF-α, IL-17A, and IL-10 levels using ELISA. Our results indicate that blood count-based ratios NLR, PLR, and MLR were significantly higher in patients compared to controls. In addition, increased systemic levels of NO, TNF-α, and IL-17A and colonic expression of iNOS and NF-κB were observed in the same patients. Interestingly, the high ratio of NLR and MLR, as well as NO production, was significantly decreased in treated patients. Collectively, our findings suggest that Nitric Oxide, as well as the blood count-based ratios (NLR, PLR, MLR), could constitute useful immuno-markers in complicated Crohn’s Disease, predicting the response to treatment

Keywords: complicated crohn’s disease, nitric oxide, blood count-based ratios, treatments, pro-inflammatory cytokines

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Authors: Mushtaq Ahmad, Bashir Rahman, Taqweem-ul-Haq, Fazal Jalil, Aftab Ali Shah

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Single nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 G/C polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC-cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated, and the association between genotypes and the risk of BC was calculated by odds ratios (OR) and confidence intervals (95%). A significant difference in genotypic frequencies (χ2=63.10; p ≤ 0.0001) and allelic frequencies (OR=0.3955 (0.3132-0.4993); p ≤ 0.0001) was observed between cases and controls. Furthermore, we also found that miR-146 rs2910164 CC homozygote increased the risk of breast cancer in the dominant (OR=0.2397 (0.1629-0.3526); p=0.0001; GG vs GC+CC) and recessive (OR=2.803 (1.865- 4.213); P ≤ 0.0001; CC vs GC+GG) inheritance models. In summary, miR-146a rs2910164 G/C is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G > C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm these findings.

Keywords: breast cancer, MIR146A, microRNA, SNP

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