Search results for: disease cluster

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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Authors: Orathai Srithongtham, Ploypailin Mekathepakorn, Tossaphong Buraman, Pontida Moonpradap, Rungrueng Kitpati, Chulapon Kratet, Worayuth Nak-ai, Suwaree Charoenmukkayanan, Peeranuch Keawkanya

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The COVID-19 pandemic was effect to the health security of the Thai people. The PHEM principle was essential to the surveillance, prevention, and control of COVID-19. This study aimed to present the process of prevention and control of COVID-19 from February 29, 2021- April 30, 2022, and the factors and conditions influent the successful outcome. The study areas were three provinces. The target group was 37 people, composed of public health personnel. The data was collected in-depth, and group interviews followed the non-structure interview guide and were analyzed by content analysis. The components of COVID-19 prevention and control were found in the process of PHEM as follows; 1) Emergency Operation Center (EOC) with an incidence command system (ICS) from the district to provincial level and to propose the provincial measure, 2) Provincial Communicable Disease Committee (PCDC) to decide the provincial measure 3) The measure for surveillance, prevention, control, and treatment of COVID-19, and 4) outcomes and best practices for surveillance and control of COVID-19. The success factors of 4S and EC were as follows; Space: prepare the quarantine (HQ, LQ), Cohort Ward (CW), field hospital, and community isolation and home isolation to face with the patient and risky group, Staff network from various organization and group cover the community leader and Health Volunteer (HV), Stuff the management and sharing of the medical and non-medical equipment, System of Covid-19 respond were EOC, ICS, Joint Investigation Team (JIT) and Communicable Disease Control Unit (CDCU) for monitoring the real-time of surveillance and control of COVID-19 output, Environment management in hospital and the community with Infections Control (IC) principle, and Culture in term of social capital on “the relationship of Isan people” supported the patient provide the good care and support. The structure of PHEM, Isan’s Culture, and good preparation was a significant factor in the three provinces.

Keywords: public health, emergency management, covid-19, pandemic

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Authors: Mohammed Al-Zubaidi, Katherine Ong, Pravin Viswambaram, Steve McCombie, Oliver Oey, Jeremy Ong, Richard Gauci, Ronny Low, Dickon Hayne

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Objective: Lymph node involvement along with distant metastasis in a patient with invasive bladder cancer determines the disease survival, therefeor, it is an essential determinant of the therapeutic management and outcome. This retrospective study aims to determine the accuracy of FDG PET scan in detecting lymphatic involvement and distant metastatic urothelial cancer compared to conventional CT staging. Method: A retrospective review of 76 patients with UC or BC who underwent surgery or confirmatory biopsy that was staged with both CT and 18F-FDG-PET (up to 8 weeks apart) between 2015 and 2020. Fifty-sevenpatients (75%) had formal pelvic LN dissection or biopsy of suspicious metastasis. 18F-FDG-PET reports for positive sites were qualitative depending on SUV Max. On the other hand, enlarged LN by RECIST criteria 1.1 (>10 mm) and other qualitative findings suggesting metastasis were considered positive in CT scan. Histopathological findings from surgical specimens or image-guided biopsies were considered the gold standard in comparison to imaging reports. 18F-FDG-avid or enlarged pelvic LNs with surgically proven nodal metastasis were considered true positives. Performance characteristics of 18F-FDG-PET and CT, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (PPV), were calculated. Results: Pelvic LN involvement was confirmed histologically in 10/57 (17.5%) patients. Sensitivity, specificity, PPV and NPV of CT for detecting pelvic LN metastases were 41.17% (95% CI:18-67%), 100% (95% CI:90-100%) 100% (95% CI:59-100%) and 78.26% (95% CI:64-89%) respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG-PET for detecting pelvic LN metastases were 62.5% (95% CI:35-85%), 83.78% (95% CI:68-94%), 62.5% (95% CI:35-85%), and 83.78% (95% CI:68-94%) respectively. Pre-operative staging with 18F-FDG-PET identified the distant metastatic disease in 9/76 (11.8%) patients who were occult on CT. This retrospective study suggested that 18F-FDG-PET may be more sensitive than CT for detecting pelvic LN metastases. 7/76 (9.2%) patients avoided cystectomy due to 18F-FDG-PET diagnosed metastases that were not reported on CT. Conclusion: 18F-FDG-PET is more sensitive than CT for pelvic LN metastases, which can be used as the standard modality of bladder cancer staging, as it may change the treatment by detecting lymph node metastasis that was occult in CT. Further research involving randomised controlled trials comparing the diagnostic yield of 18F-FDG-PET and CT in detecting nodal and distant metastasis in UC or BC is warranted to confirm our findings.

Keywords: FDG PET, CT scan, urothelial cancer, bladder cancer

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Authors: Peter K. Galenko, Stefanie Koch, Markus Rettenmayr, Robert Wonneberger, Evgeny V. Kharanzhevskiy, Maria Zamoryanskaya, Vladimir Ankudinov

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We analyze the structure of undercooled melts, crystal growth kinetics and amorphous/crystalline microstructure of rapidly solidifying glass-forming Pd-based and CuZr-based alloys. A dendrite growth model is developed using a combination of the kinetic phase-field model and mesoscopic sharp interface model. The model predicts features of crystallization kinetics in alloys from thermodynamically controlled growth (governed by the Gibbs free energy change on solidification) to the kinetically limited regime (governed by atomic attachment-detachment processes at the solid/liquid interface). Comparing critical undercoolings observed in the crystallization kinetics with experimental data on melt viscosity, atomistic simulation's data on liquid microstructure and theoretically predicted dendrite growth velocity allows us to conclude that the dendrite growth kinetics strongly depends on the cluster structure changes of the melt. The obtained data of theoretical and experimental investigations are used for interpretation of microstructure of samples processed in electro-magnetic levitator on board International Space Station in the frame of the project "MULTIPHAS" (European Space Agency and German Aerospace Center, 50WM1941) and "KINETIKA" (ROSKOSMOS).

Keywords: dendrite, kinetics, model, solidification

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Authors: Patarapan Odton

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This study investigates demographic and socio-economic factors of breastfeeding practice, including exclusively breastfeeding among children in Thailand using the Multiple Indicator Cluster Survey (MICS3 and MICS4). Logistic regression models were used to examine the determinants of initial breastfeeding, exclusively breastfeeding, and predominant breastfeeding, using data from women and children section of the survey. For initial breastfeeding, women live in rural area were more likely to start breastfeeding within one day of birth rather than who live in urban area in both round of the surveys. In year 2012, there were significantly higher probabilities of women in rural area started breastfeeding within one hour of birth compare to urban area. Women in southern Thailand have higher probabilities of start breastfeeding within one hour and one day than women in Bangkok and central region. During the year 2005-2006, children aged less than 5 years old lived in rural area have been breastfed higher than children in urban area. Children live in the northeast region were more likely to have been breastfed than the other regions. Only the second wealth quintile group was significant higher probability of ever been breastfed than the poorest group. The findings in the second round of the survey are different from the year 2005-06. In 2012, there was no difference in probability of ever been breastfed among children live in urban and rural area, children in Bangkok and central region were less probability of ever been breastfed than the others.

Keywords: Breastfeeding, Exclusive Breastfeeding, Predominant Breastfeeding, Urban-Rural Difference

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Authors: Poonam Goswami

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Background: The diagnosis of a serious illness like cancer can have an impact on a patient’s emotional well-being and may result in psychological symptoms, anxiety, depression, and loss of control. Advance care planning discussions ensure patients’ values and goals of care, including patients’ freedom to choose their place of death, are respected. Unfortunately, these discussions are often delayed and are not initiated early in patients’ cancer trajectory. As a result, patients’ wishes often remains unknown until the last phase of their life. Evidence suggests that many patients inappropriately receive aggressive treatment near the end of life, which does lead to higher resource utilization, decreased quality of life, and increased cost. Additionally, the novel coronavirus disease 2019 (COVID-19) pandemic challenged the health care systems worldwide and raised important ethical issues, especially regarding the potential need for rationing health care in the context of scarce resources and crisis capacity. The importance of goal concordant care is now even substantially important and is heightened in the context of this pandemic. Problem: Although there is growing evidence on the effects of the ACP on the completion of advanced directives, improved patient and family concordance for preferences for medical care, and receipt of care, there is still a lack of standardized ACP conversation strategies for patients with cancer. Methods: The Key concepts of ACP include (1) assessing patient and family readiness, (2) identifying a surrogate decision maker ( medical power of attorney), (3) exploring patient and family understanding of the disease and treatment options,(4) discussing the values and goals of care, and options for end-of-life care, (5) documenting patient preferences in the medical record, and (6) revisiting the discussions at every change in the treatment plan and /or change in clinical status, including at every hospitalization. Conclusion/Implication for practice: Advance Care Planning (ACP) and end-of-life (EOL) discussions are important for patients, families, and health care providers. Adopting the verbal and nonverbal communication strategies can help overcome the barriers to effective communication on these difficult discussions. ACP with goals of care discussions should not be delayed until the patient is hospitalized.

Keywords: advance care planning, end of life, cancer, global, pandemic

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Authors: Yuguang Gao, Mingtao Deng

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The integration of independently operating hospitals into a unified healthcare service system has become a strategic imperative in the pursuit of hospitals’ high-quality development. Central to the concept of group governance over such transformation, exemplified by a collaborative medical alliance, is the delineation of shared value, vision, and goals. Given the inherent disparity in capabilities among hospitals within the alliance, particularly in the treatment of different diseases characterized by Disease Related Groups (DRG) in terms of effectiveness, efficiency and resource utilization, this study aims to address the centralized decision-making of intra-hospital patient referral within the medical alliance to enhance the overall production and quality of service provided. We first introduce the notion of production utility, where a higher production utility for a hospital implies better performance in treating patients diagnosed with that specific DRG group of diseases. Then, a Discrete-Event Simulation (DES) framework is established for patient referral among hospitals, where patient flow modeling incorporates a queueing system with fixed capacities for each hospital. The simulation study begins with a two-member alliance. The pivotal strategy examined is a "whether-to-refer" decision triggered when the bed usage rate surpasses a predefined threshold for either hospital. Then, the decision encompasses referring patients to the other hospital based on DRG groups’ production utility differentials as well as bed availability. The objective is to maximize the total production utility of the alliance while minimizing patients’ average length of stay and turnover rate. Thus the parameter under scrutiny is the bed usage rate threshold, influencing the efficacy of the referral strategy. Extending the study to a three-member alliance, which could readily be generalized to multi-member alliances, we maintain the core setup while introducing an additional “which-to-refer" decision that involves referring patients with specific DRG groups to the member hospital according to their respective production utility rankings. The overarching goal remains consistent, for which the bed usage rate threshold is once again a focal point for analysis. For the two-member alliance scenario, our simulation results indicate that the optimal bed usage rate threshold hinges on the discrepancy in the number of beds between member hospitals, the distribution of DRG groups among incoming patients, and variations in production utilities across hospitals. Transitioning to the three-member alliance, we observe similar dependencies on these parameters. Additionally, it becomes evident that an imbalanced distribution of DRG diagnoses and further disparity in production utilities among member hospitals may lead to an increase in the turnover rate. In general, it was found that the intra-hospital referral mechanism enhances the overall production utility of the medical alliance compared to individual hospitals without partnership. Patients’ average length of stay is also reduced, showcasing the positive impact of the collaborative approach. However, the turnover rate exhibits variability based on parameter setups, particularly when patients are redirected within the alliance. In conclusion, the re-structuring of diagnostic disease groups within the medical alliance proves instrumental in improving overall healthcare service outcomes, providing a compelling rationale for the government's promotion of patient referrals within collaborative medical alliances.

Keywords: collaborative medical alliance, disease related group, patient referral, simulation

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Authors: Md. Abu Sufian, Robiqul Islam, Imam Hossain Shajid, Mahesh Hanumanthu, Jarasree Varadarajan, Md. Sipon Miah, Mingbo Niu

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Coronary Heart Disease (CHD) remains a principal cause of global morbidity and mortality, characterized by atherosclerosis—the build-up of fatty deposits inside the arteries. The study introduces an innovative methodology that leverages cloud-based platforms like AWS Live Streaming and Artificial Intelligence (AI) to early detect and prevent CHD symptoms in web applications. By employing novel simulation processes and AI algorithms, this research aims to significantly mitigate the health and societal impacts of CHD. Methodology: This study introduces a novel simulation process alongside a multi-phased model development strategy. Initially, health-related data, including heart rate variability, blood pressure, lipid profiles, and ECG readings, were collected through user interactions with web-based applications as well as API Integration. The novel simulation process involved creating synthetic datasets that mimic early-stage CHD symptoms, allowing for the refinement and training of AI algorithms under controlled conditions without compromising patient privacy. AWS Live Streaming was utilized to capture real-time health data, which was then processed and analysed using advanced AI techniques. The novel aspect of our methodology lies in the simulation of CHD symptom progression, which provides a dynamic training environment for our AI models enhancing their predictive accuracy and robustness. Model Development: it developed a machine learning model trained on both real and simulated datasets. Incorporating a variety of algorithms including neural networks and ensemble learning model to identify early signs of CHD. The model's continuous learning mechanism allows it to evolve adapting to new data inputs and improving its predictive performance over time. Results and Findings: The deployment of our model yielded promising results. In the validation phase, it achieved an accuracy of 92% in predicting early CHD symptoms surpassing existing models. The precision and recall metrics stood at 89% and 91% respectively, indicating a high level of reliability in identifying at-risk individuals. These results underscore the effectiveness of combining live data streaming with AI in the early detection of CHD. Societal Implications: The implementation of cloud-based AI for CHD symptom detection represents a significant step forward in preventive healthcare. By facilitating early intervention, this approach has the potential to reduce the incidence of CHD-related complications, decrease healthcare costs, and improve patient outcomes. Moreover, the accessibility and scalability of cloud-based solutions democratize advanced health monitoring, making it available to a broader population. This study illustrates the transformative potential of integrating technology and healthcare, setting a new standard for the early detection and management of chronic diseases.

Keywords: coronary heart disease, cloud-based ai, machine learning, novel simulation techniques, early detection, preventive healthcare

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Authors: Zekang Lan, Yan Xu, Yingkun Huang, Dian Huang, Shengzhong Feng

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Jobs on high-performance computing (HPC) clusters can suffer significant performance degradation due to inter-job network interference. Topology-aware job allocation problem (TJAP) is such a problem that decides how to dedicate nodes to specific applications to mitigate inter-job network interference. In this paper, we study the window-based TJAP on a fat-tree network aiming at minimizing the cost of communication hop, a defined inter-job interference metric. The window-based approach for scheduling repeats periodically, taking the jobs in the queue and solving an assignment problem that maps jobs to the available nodes. Two special allocation strategies are considered, i.e., static continuity assignment strategy (SCAS) and dynamic continuity assignment strategy (DCAS). For the SCAS, a 0-1 integer programming is developed. For the DCAS, an approach called neural simulated algorithm (NSA), which is an extension to simulated algorithm (SA) that learns a repair operator and employs them in a guided heuristic search, is proposed. The efficacy of NSA is demonstrated with a computational study against SA and SCIP. The results of numerical experiments indicate that both the model and algorithm proposed in this paper are effective.

Keywords: high-performance computing, job allocation, neural simulated annealing, topology-aware

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Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

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Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 191

Authors: Atlal El-Assaad

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Viruses change with time through mutations and result in new variants that may persist or disappear. A Mutation refers to an actual change in the virus genetic sequence, and a variant is a viral genome that may contain one or more mutations. Critical mutations may cause the virus to be more transmissible, with high disease severity, and more vulnerable to diagnostics, therapeutics, and vaccines. Thus, variants carrying such mutations may increase the risk to human health and are considered variants of concern (VOC). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the contagious in humans, positive-sense single-stranded RNA virus that caused coronavirus disease 2019 (COVID-19) - has been studied thoroughly, and several variants were revealed across the world with their corresponding mutations. SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins, but prior study and vaccines development focused on genetic mutations in the S protein due to its vital role in allowing the virus to attach and fuse with the membrane of a host cell. Specifically, subunit S1 catalyzes attachment, whereas subunit S2 mediates fusion. In this perspective, we studied all charged amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 in a crystal structure and assessed the effect of different mutations. We generated all missense mutants of SARS-CoV-2 protein amino acids (AAs) within the SARS-CoV-2:CC12.1 complex model. To generate the family of mutants in each complex, we mutated every charged amino acid with all other charged amino acids (Lysine (K), Arginine (R), Glutamic Acid (E), and Aspartic Acid (D)) and studied the new binding of the complex after each mutation. We applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations to determine the effect of each mutation on binding. After analyzing our data, we identified charged amino acids keys for binding. Furthermore, we validated those findings against published experimental genetic data. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants found worldwide.

Keywords: SARS-CoV-2, variant, ionic amino acid, protein-protein interactions, missense mutation, AESOP

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Authors: Joanna Marie A. Paulino-Morente, Vaneza Valentina L. Penolio, Grace Sabado

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Ovarian cancer is extremely hard to diagnose in its early stages, and those afflicted at the time of diagnosis are typically asymptomatic and in the late stages of the disease, with metastasis to other organs. Ovarian cancers often occur sporadically, with only 5% associated with hereditary mutations. Mutations in the BRCA1 and BRCA2 tumor suppressor genes have been found to be responsible for the majority of hereditary ovarian cancers. One type of ovarian tumor is Malignant Mixed Mullerian Tumor (MMMT), which is a very rare and aggressive type, accounting for only 1% of all ovarian cancers. Reported is a case of a 43-year-old G3P3 (3003), who came into our institution due to a 2-month history of difficulty of breathing. Family history reveals that her eldest and younger sisters both died of ovarian malignancy, with her younger sister having a histopathology report of endometrioid ovarian carcinoma, left ovary stage IIIb. She still has 2 asymptomatic sisters. Physical examination pointed to pleural effusion of right lung, and presence of bilateral ovarian new growth, which had a Sassone score of 13. Admitting Diagnosis was G3P3 (3003), Ovarian New Growth, bilateral, Malignant; Pleural effusion secondary to malignancy. BRCA was requested to establish a hereditary mutation; however, the patient had no funds. Once the patient was stabilized, TAHBSO with surgical staging was performed. Intraoperatively, the pelvic cavity was occupied by firm, irregularly shaped ovaries, with a colorectal metastasis. Microscopic sections from both ovaries and the colorectal metastasis had pleomorphic tumor cells lined by cuboidal to columnar epithelium exhibiting glandular complexity, displaying nuclear atypia and increased nuclear-cytoplasmic ratio, which are infiltrating the stroma, consistent with the features of Malignant Mixed Mullerian Tumor, since MMMT is composed histologically of malignant epithelial and sarcomatous elements. In conclusion, discussed is the clinic-pathological feature of a patient with primary ovarian Malignant Mixed Mullerian Tumor, a rare malignancy comprising only 1% of all ovarian neoplasms. Also, by understanding the hereditary ovarian cancer syndromes and its relation to this patient, it cannot be overemphasized that a comprehensive family history is really fundamental for early diagnosis. The familial association of the disease, given that the patient has two sisters who were diagnosed with an advanced stage of ovarian cancer and succumbed to the disease at a much earlier age than what is reported in the general population, points to a possible hereditary syndrome which occurs in only 5% of ovarian neoplasms. In a low-resource setting, being in a third world country, the following will be recommended for monitoring and/or screening women who are at high risk for developing ovarian cancer, such as the remaining sisters of the patient: 1) Physical examination focusing on the breast, abdomen, and rectal area every 6 months. 2) Transvaginal sonography every 6 months. 3) Mammography annually. 4) CA125 for postmenopausal women. 5) Genetic testing for BRCA1 and BRCA2 will be reserved for those who are financially capable.

Keywords: BRCA, hereditary breast-ovarian cancer syndrome, malignant mixed mullerian tumor, ovarian cancer

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Authors: Zoltan Horvath, Dora Nagy

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In this research, it was examined whether individual COVID variants cause differences in the lactate curve of cyclists. After all, the virus variants attacked different organs in our body during the infections. During our tests, we used a traditional lactate step test, the results of which were compared with the values before the infection. In the tests, it has been proven that different virus variants show unique lactate curves. In this way, based on the lactate curve, it is possible to identify which variant caused the disease. Thanks to this, it has been shorten the return time, because we can apply the best return protocol after infection to the competitors.

Keywords: COVID-Sars19, lactate, virus mutation, lactate profile

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Authors: Seemab Safdar, Shazia Fatima, Ahmad Qureshy, M. Adnan Saeed, M. Faheem

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Background: Thyroid cancer has 586,000 cases per year worldwide, and this translates to 3% of all tumor diagnoses. 90% of the cases fall under differentiated thyroid carcinoma (DTC), which includes follicular thyroid cancer (FTC) and papillary thyroid cancer (PTC). During their illness, 10% of patients develop distant metastases, and two-thirds of them develop resistance to radioactive iodine (RAI) treatment. It has been shown that in some circumstances, like DTC with high TG levels and negative 131I whole-body scintigraphy (TENIS), [18F] FDG-PET-CT is an effective imaging technique. This study determines the role of [18F] FDG-PET-CT in the treatment of TENIS patients. Methods: 16 patients (n = 12 female; 4 males, age 45 ± 15 years) with histologically proven thyroid cancer (Differentiated and poorly differentiated) and high TG with negative iodine scans were included in this prospective study from January 2024 to June 2024. They underwent scanning in state-of-the-art (GE Discovery MI) [18F] FDG-PET-CT for re-staging or diagnostics of recurrent disease using a standardized protocol. All DTC subtypes and PDTC were included. The referring physicians completed standardized questionnaires both before and after PET-CT to prospectively determine the examination's effect on clinical decision-making. Patient outcomes were measured by analysis of medical records. Moreover, after PET-CT, a change in the pre-PET-CT planned therapies was documented in 32% of cases and additional invasive diagnostic procedures could be waived in 37.5 % of cases. TG levels under TSH stimulation were significantly higher in patients showing PET-CT metastases compared to patients without such findings (68.75%). Results: Without PET-CT, physicians referring to the doctors had not established a complete treatment plan for 45% of patients with thyroid carcinoma. 12/16 patients showed FDG avidity in cervical lymph nodes that were not Iodine avid previously, 2 patients had FDG avid disease in the lungs. In the process, PET-CT helped plan patient management and created a clear plan for treatment in 68.75% of patients. Conclusions: This study confirms that [18F] FDG-PET-CT used in a routine clinical setting has a very important impact on the management of patients with thyroid cancer when TG levels are persistently high in the presence of negative Iodine Scans by initiating treatments and replacing additional imaging and invasive tests.

Keywords: PET-CT, TENIS, role, FDG

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Authors: Ghebremedhin Tsegay, Weldu Tesfagaber, Yuanmao Zhu, Xijun He, Wan Wang, Zhenjiang Zhang, Encheng Sun, Jinya Zhang, Yuntao Guan, Fang Li, Renqiang Liu, Zhigao Bu, Dongming Zhao*

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African swine fever (ASF) is a highly infectious viral disease of pigs, resulting in significant economic loss worldwide. As there is no approved vaccines and treatments, the control of ASF entirely depends on early diagnosis and culling of infected pigs. Thus, highly specific and sensitive diagnostic assays are required for accurate and early diagnosis of ASF virus (ASFV). Currently, only a few recombinant proteins have been tested and validated for use as reagents in ASF diagnostic assays. The most promising ones for ASFV antibody detection were p72, p30, p54, and pp62. So far, three ELISA kits based on these recombinant proteins have been commercialized. Due to the complex nature of the virus and variety forms of the disease, robust serodiagnostic assays are still required. ASFV p22 protein, encoded by KP177R gene, is located in the inner membrane of viral particle and appeared transiently in the plasma membrane early after virus infection. The p22 protein interacts with numerous cellular proteins, involved in processes of phagocytosis and endocytosis through different cellular pathways. However, p22 does not seem to be involved in virus replication or swine pathogenicity. In this study, E.coli expressed recombinant p22 protein was used to generate a monoclonal antibody (mAb), and its potential use for the development of blocking ELISA (bELISA) was evaluated. A total of 806 pig serum samples were tested to evaluate the bELISA. Acording the ROC (Reciever operating chracteristic) analysis, 100% sensitivity and 98.10% of specificity was recorded when the PI cut-off value was set at 47%. The novel assay was able to detect the antibodies as early as 9 days post infection. Finaly, a highly sensitive, specific and rapid novel p22-mAb based bELISA assay was developed, and optimized for detection of antibodies against genotype I and II ASFVs. It is a promising candidate for an early and acurate detection of the antibodies and is highly expected to have a valuable role in the containment and prevention of ASF.

Keywords: ASFV, blocking ELISA, diagnosis, monoclonal antibodies, sensitivity, specificity

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Authors: Elmeliani M’Hammed

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The work is carried out for the synthesis of antifungal effective against the fungus Fusarium oxysporum, Albedinis (Foa), the causative agent of bayoud, dates palm disease, through the use of raw clay as a green catalyst. The Aza-Michael reaction of amine addition to α, β-unsaturated alkene was carried out using the crude clay as a green catalyst to synthesize the antifungal agent bayoud. The reaction was carried out under favorable conditions, ambient temperature, without solvent, and a green catalyst "loves the environment" that the product that was synthesized gave us a high yield and excellent chemo selectivity.

Keywords: raw clay, amines, alkenes, environment, antifungal, bayoud, date palms

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Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

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Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: Africa Makasi

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The research explored factors influencing the adoption of disruptive technologies in the mobile telecommunications industry in Zimbabwe. Data was gathered from the second biggest competitor in the industry with over 3 million subscribers as the main case of study. The survey was conducted by purposively selecting 70 respondents from a population of 3,000,000 (three million) active subscribers from the company’s database. A skip interval of 42,857 was used to randomly select the sample. Customer representatives were selected from the company’s five regional offices using a two-stage cluster sampling technique. Employee participants were purposively selected from the company’s head office. Self-administered questionnaires were used in the research. A pilot test was conducted and the assessment of the reliability of the research instruments used in the research performed. Results of the pilot study were analyzed to test for reliability using SPSS. The results confirmed that the style of leadership and its thrust may help speed up or reduce the adoption of disruptive technologies. This was reflected by a p–value of 0.01 which is less than 0.05. The null hypothesis was thus rejected and the strong relationship between leadership and adoption of disruptive technology is confirmed. Similar results were also obtained with respect to staff competence, availability of funding and the type of infrastructure available Future research should look at organizational ambidexterity as well as exploitation and exploration paradigms in organizations in the telecommunications industry and their impact on the adoption of disruptive technologies.

Keywords: disruptive innovation, adoption, mobile telecommunication industry, exploration and exploitation

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Authors: R. Pardo, P. Menendez, MA Gil-Olarte, S. Sanchez, E. García, R. Quintana, J. Martín

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Introduction : Within oncoplastic breast techniques there is increased interest in immediate partial breast reconstruction. The volume resected is greater than that of conventional conservative techniques. Central tumours of the breast have classically been treated with a mastectomy with regard to oncological safety and cosmetic secondary effects after wide central resection of the nipple and breast tissue beneath. Oncological results for central quadrantectomy have a recurrence level, disease- free period and survival identical to mastectomy. Grissoti flap is an oncoplastic surgical technique that allows the surgeon to perform a safe central quadrantectomy with excellent cosmetic results. Material and methods: The Grissoti flap is a glandular cutaneous advancement rotation flap that can fill the defect in the central portion of the excised breast. If the inferior border is affected by tumour and further surgery is decided upon at the Multidisciplinary Team Meeting, it will be necessary to perform a mastectomy. All patients with a Grisotti flap undergoing surgery since 2009 were reviewed obtaining the following data: age, hystopathological diagnosis, size, operating time, volume of tissue resected, postoperative admission time, re-excisions due to positive margins affected by tumour, wound dehiscence, complications and recurrence. Analysis and results of sentinel node biopsy were also obtained. Results: 12 patients underwent surgery between 2009-2015. The mean age was 54 years (34-67) . All had a preoperative diagnosis of ductal infiltrative carcinoma of less than 2 cm,. Diagnosis was made with Ultrasound, Mamography or both . Magnetic resonance was used in 5 cases. No patients had preoperative positive axilla after ultrasound exploration. Mean operating time was 104 minutes (84-130). Postoperative stay was 24 hours. Mean volume resected was 159 cc (70-286). In one patient the surgical border was affected by tumour and a further procedure with resection of the affected border was performed as ambulatory surgery. The sentinel node biopsy was positive for micrometastasis in only two cases. In one case lymphadenectomy was performed in 2009. In the other, treated in 2015, no lymphadenectomy was performed as the patient had a favourable histopathological prognosis and the multidisciplinary team meeting agreed that lymphadenectomy was not required. No recurrence has been diagnosed in any of the patients who underwent surgery and they are all disease free at present. Conclusions: Conservative surgery for retroareolar central tumours of the breast results in good local control of the disease with free surgical borders, including resection of the nipple areola complex and pectoral major muscle fascia. Reconstructive surgery with the inferior Grissoti flap adequately fills the defect after central quadrantectomy with creation of a new cutaneous disc where a new nipple areola complex is reconstructed with a local flap or micropigmentation. This avoids the need for contralateral symmetrization. Sentinel Node biopsy can be performed without added morbidity. When feasible, the Grissoti flap will avoid skin-sparing mastectomy for central breast tumours that will require the use of an expander, prosthesis or myocutaneous flap, with all the complications of a more complex operation.

Keywords: Grisotti flap, oncoplastic surgery, central tumours, breast

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Authors: Ji-Chan Jang

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Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.

Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis

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Authors: Sergey Kopysov, Nikita Nedozhogin, Leonid Tonkov

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The article presents a parallel iterative solver for large sparse linear systems which can be used on a heterogeneous platform. Traditionally, the problem of solving linear systems does not scale well on multi-CPU/multi-GPUs clusters. For example, most of the attempts to implement the classical conjugate gradient method were at best counted in the same amount of time as the problem was enlarged. The paper proposes the pipelined variant of the conjugate gradient method (PCG), a formulation that is potentially better suited for hybrid CPU/GPU computing since it requires only one synchronization point per one iteration instead of two for standard CG. The standard and pipelined CG methods need the vector entries generated by the current GPU and other GPUs for matrix-vector products. So the communication between GPUs becomes a major performance bottleneck on multi GPU cluster. The article presents an approach to minimize the communications between parallel parts of algorithms. Additionally, computation and communication can be overlapped to reduce the impact of data exchange. Using the pipelined version of the CG method with one synchronization point, the possibility of asynchronous calculations and communications, load balancing between the CPU and GPU for solving the large linear systems allows for scalability. The algorithm is implemented with the combined use of technologies: MPI, OpenMP, and CUDA. We show that almost optimum speed up on 8-CPU/2GPU may be reached (relatively to a one GPU execution). The parallelized solver achieves a speedup of up to 5.49 times on 16 NVIDIA Tesla GPUs, as compared to one GPU.

Keywords: conjugate gradient, GPU, parallel programming, pipelined algorithm

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Authors: Shlomit Paz, Meir Broza

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Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period and produces an enterotoxin that causes copious, painless, watery diarrhoea that can quickly lead to severe dehydration and death if treatment is not promptly given. In an epidemic, the source of the contamination is usually the feces of an infected person. The disease can spread rapidly in areas with poor treatment of sewage and drinking water. Cholera remains a global threat and is one of the key indicators of social development. An estimated 3-5 million cases and over 100,000 deaths occur each year around the world. The relevance of climatic events as causative factors for cholera epidemics is well known. However, the examination of the involvement of winds in intra-continental disease distribution is new. The study explore the hypothesis that the spreading of cholera epidemics may be related to the dominant wind direction over land by presenting the influence of the wind direction on windborn dissemination by flying insects, which may serve as vectors. Chironomids ("non-biting midges“) exist in the majority of freshwater aquatic habitats, especially in estuarine and organic-rich water bodies typical to Vibrio cholerae. Chironomid adults emerge into the air for mating and dispersion. They are highly mobile, huge in number and found frequently in the air at various elevations. The huge number of chironomid egg masses attached to hard substrate on the water surface, serve as a reservoir for the free-living Vibrio bacteria. Both male and female, while emerging from the water, may carry the cholera bacteria. In experimental simulation, it was demonstrated that the cholera-bearing adult midges are carried by the wind, and transmit the bacteria from one body of water to another. In our previous study, the geographic diffusions of three cholera outbreaks were examined through their linkage with the wind direction: a) the progress of Vibrio cholerae O1 biotype El Tor in Africa during 1970–1971 and b) again in 2005–2006; and c) the rapid spread of Vibrio cholerae O139 over India during 1992–1993. Using data and map of cholera dissemination (WHO database) and mean monthly SLP and geopotential data (NOAA NCEP-NCAR database), analysis of air pressure data at sea level and at several altitudes over Africa, India and Bangladesh show a correspondence between the dominant wind direction and the intra-continental spread of cholera. The results support the hypothesis that aeroplankton (the tiny life forms that float in the air and that may be caught and carried upward by the wind, landing far from their origin) carry the cholera bacteria from one body of water to an adjacent one. In addition to these findings, the current follow-up study will present new results regarding the possible involvement of winds in the spreading of cholera in recent outbreaks (2010-2013). The findings may improve the understanding of how climatic factors are involved in the rapid distribution of new strains throughout a vast continental area. Awareness of the aerial transfer of Vibrio cholerae may assist health authorities by improving the prediction of the disease’s geographic dissemination.

Keywords: cholera, Vibrio cholerae, wind direction, Vibrio cholerae dissemination

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Authors: Eti Dwi Wiraningsih, Folashade Agusto, Lina Aryati, Syamsuddin Toaha, Suzanne Lenhart, Widodo, Willy Govaerts

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This paper considers a deterministic model for the transmission dynamics of rabies virus in the wild dogs-domestic dogs-human zoonotic cycle. The effect of vaccination and culling in dogs is considered on the model, then the stability was analysed to get basic reproduction number. We use the next generation matrix method and Routh-Hurwitz test to analyze the stability of the Disease-Free Equilibrium and Endemic Equilibrium of this model.

Keywords: stability analysis, rabies model, vaccination effect, culling in dogs

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Authors: Strahinja Kovačević, Sanja Podunavac-Kuzmanović, Lidija Jevrić, Milica Karadžić

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The present study is based on the quantitative structure-activity relationship (QSAR) analysis of eighteen compounds with anti-prion activity. The structures and anti-prion activities (expressed in response units, RU%) of the analyzed compounds are taken from CHEMBL database. In the first step of analysis 85 molecular descriptors were calculated and based on them the hierarchical cluster analysis (HCA) and principal component analysis (PCA) were carried out in order to detect potential significant similarities or dissimilarities among the studied compounds. The calculated molecular descriptors were physicochemical, lipophilicity and ADMET (absorption, distribution, metabolism, excretion and toxicity) descriptors. The first stage of the QSAR analysis was simple linear regression modeling. It resulted in one acceptable model that correlates Henry's law constant with RU% units. The obtained 2D-QSAR model was validated by cross-validation as an internal validation method. The validation procedure confirmed the model’s quality and therefore it can be used for prediction of anti-prion activity. The next stage of the analysis of anti-prion activity will include 3D-QSAR and molecular docking approaches in order to select the most promising compounds in treatment of prion diseases. These results are the part of the project No. 114-451-268/2016-02 financially supported by the Provincial Secretariat for Science and Technological Development of AP Vojvodina.

Keywords: anti-prion activity, chemometrics, molecular modeling, QSAR

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Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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Authors: Mostafa Mohammadpour, Christoph Kapeller, Christy Li, Josef Scharinger, Christoph Guger

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Interictal spikes provide valuable information on electrocorticography (ECoG), which aids in surgical planning for patients who suffer from refractory epilepsy. However, the shape and temporal dynamics of these spikes remain unclear. The purpose of this work was to analyze the shape of interictal spikes and measure their distance to the seizure onset zone (SOZ) to use in epilepsy surgery. Thirteen patients' data from the iEEG portal were retrospectively studied. For analysis, half an hour of ECoG data was used from each patient, with the data being truncated before the onset of a seizure. Spikes were first detected and grouped in a sequence, then clustered into interictal epileptiform discharges (IEDs) and non-IED groups using two-step clustering. The distance of the spikes from IED and non-IED groups to SOZ was quantified and compared using the Wilcoxon rank-sum test. Spikes in the IED group tended to be in SOZ or close to it, while spikes in the non-IED group were in distance of SOZ or non-SOZ area. At the group level, the distribution for sharp wave, positive baseline shift, slow wave, and slow wave to sharp wave ratio was significantly different for IED and non-IED groups. The distance of the IED cluster was 10.00mm and significantly closer to the SOZ than the 17.65mm for non-IEDs. These findings provide insights into the shape and spatiotemporal dynamics of spikes that could influence the network mechanisms underlying refractory epilepsy.

Keywords: spike propagation, spike pattern, clustering, SOZ

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Authors: Abu S. Mustafa, Mohammad W. Khan, Faraz Shaheed Khan, Nazima Habibi

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Brucellosis is a zoonotic disease of worldwide prevalence. There are at least four species and several strains of Brucella that cause human disease. Brucella genomes have very limited variation across strains, which hinder strain identification using classical molecular techniques, including PCR and 16 S rDNA sequencing. The aim of this study was to perform whole genome sequencing of clinical isolates of Brucella and perform bioinformatics and comparative genomics analyses to determine the existence of genetic differences across the isolates of a single Brucella species and strain. The draft sequence data were generated from 15 clinical isolates of Brucella melitensis (biovar 2 strain 63/9) using MiSeq next generation sequencing platform. The generated reads were used for further assembly and analysis. All the analysis was performed using Bioinformatics work station (8 core i7 processor, 8GB RAM with Bio-Linux operating system). FastQC was used to determine the quality of reads and low quality reads were trimmed or eliminated using Fastx_trimmer. Assembly was done by using Velvet and ABySS softwares. The ordering of assembled contigs was performed by Mauve. An online server RAST was employed to annotate the contigs assembly. Annotated genomes were compared using Mauve and ACT tools. The QC score for DNA sequence data, generated by MiSeq, was higher than 30 for 80% of reads with more than 100x coverage, which suggested that data could be utilized for further analysis. However when analyzed by FastQC, quality of four reads was not good enough for creating a complete genome draft so remaining 11 samples were used for further analysis. The comparative genome analyses showed that despite sharing same gene sets, single nucleotide polymorphisms and insertions/deletions existed across different genomes, which provided a variable extent of diversity to these bacteria. In conclusion, the next generation sequencing, bioinformatics, and comparative genome analysis can be utilized to find variations (point mutations, insertions and deletions) across different genomes of Brucella within a single strain. This information could be useful in surveillance and epidemiological studies supported by Kuwait University Research Sector grants MI04/15 and SRUL02/13.

Keywords: brucella, bioinformatics, comparative genomics, whole genome sequencing

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Authors: Farideh Doostan, Sahar Mohseni Taklloo, Mohammad Nosrati

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Chronic diseases are non-communicable and largely preventable by lifestyle changes including healthy diet consumption. They are the most common cause of death in the world and projected to increase by 15% globally between 2010 and 2020.The hazardous effects of behavioral and dietary risk factors on chronic disease have been established in prospective cohort studies and randomized trials. Because of some changes occur in college students’ lifestyle, assessment of dietary risk factors is important in these populations. Objective: This research was the first study that conducted to evaluate dietary intakes of Kermanian college students with WHO/FAO nutritional objectives. Material and Methods: In this descriptive cross-sectional study, 229 healthy college students of health faculty in Kerman University of Medical Sciences that do not intake any medical drugs were recruited using multistage sampling in 2013.Usual dietary intake was collected using a valid Food Frequency Questionnaire (FFQ) and diet quality was calculated based on WHO nutrient goals. To analysis of data between two groups, independent sample t. test and man whitney were applied. Results: Two hundred and twenty-nine college students; 151 females (65.9%) and 78 males (34.1%), the mean age of 21.9 years were studied. The mean of the Body Mass Index (Kg/m2) and Waist Circumference (cm) in males were 22.34 ±3.52 and 80.76±11.16 and in females were 21.19±2.62 and 73.67±7.65 respectively. Mean of daily cholesterol intake in males was significantly more than females (305±101 VS 268±98; P=0.008) and more than WHO/FAO recommendation (less than 300 mg/day). The mean of daily sodium intake in men and women were 10.4±1 and 10.9±5.3 respectively. These amounts were more than WHO/FAO recommendation (less than 2g/day). In addition, women were consumed fruit and vegetables more than men (839±336 VS 638±281; p ‹ 0.001) and these amounts were more than WHO/FAO recommendation (more than 400g/day) in both groups. Other intake indices were in the range of WHO/FAO recommendations, So that Percent of calories intake from total fat, saturated fatty acids, polyunsaturated fatty acids and added sugar were in compliance with WHO/FAO recommendations. Conclusion: Cholesterol intake in men and sodium intake in all participants were more than WHO/FAO recommendation. These dietary components are the most important causes of cardiovascular disease (one of the main causes of death in our population). These results indicated that proper nutritional education and interventions are needed in this population.

Keywords: college students, food intake, WHO /FAO nutrient intake goals, Kerman

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Authors: A. Mirzaei, S. Zolghadri, M. Athari-Allaf, H. Yousefnia, A. R. Jalilian

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Rheumatoid arthritis is the most common autoimmune disease, leading to the destruction of the joints. The aim of this study was the preparation of 90Y-chitosan complex as a novel agent for radiosynovectomy. The complex was prepared in the diluted acetic acid solution. At the optimized condition, the radiochemical purity of higher than 99% was obtained by ITLC method on Whatman No. 1 and by using a mixture of methanol/water/acetic acid (4:4:2) as the mobile phase. The complex was stable in acidic media (pH=3) and its radiochemical purity was above 98% even after 48 hours. The biodistribution data in rats showed that there was no significant leakage of the injected activity even after 48 h. Considering all of the excellent features of the complex, 90Y-chitosan can be used to manipulate synovial inflammation effectively.

Keywords: chitosan, Y-90, radiosynovectomy, biodistribution

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