Search results for: clinical prediction score

Authors: Elron Fouten

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Recently, debates surrounding the social relevance of psychology in South Africa have focussed on how the growing neoliberal rationality within academia has again resulted in the discipline catering to the needs of powerful social groupings to protect its own economic interests, rather than producing socially relevant knowledge. Consequently, this study aimed to conduct a content analysis of the recent research output of psychology masters students, to establish whether it has produced research that addresses local and national psychosocial issues and as such deemed socially relevant knowledge. The study sampled clinical, counselling, and research psychology masters theses from 16 South African universities submitted between 1998 and 2017. Overall, 2001 theses were sampled, which were analysed using qualitative content analysis predominantly based on the descriptive categories identified in similar studies using published journal articles. Results indicated that empirical qualitative theses, using systems-oriented theory and post-modern frameworks were most prevalent. Further, traditional topics within psychology had relatively more weighting compared to more social topics. Although a significant number of theses recruited participants from working-class or poor backgrounds, there was an overreliance on participants from urban areas located in some of the country’s wealthiest provinces. Despite a strong adult-centric focus, trends regarding participants’ race and gender roughly resembled current population demographics. Overall, the results indicate that psychology in South Africa, at least at university-level, is to some extent trying to engage with national psychosocial concerns. However, there are still several key areas which need to be addressed to ensure the continued social relevance of the discipline.

Keywords: adult-centric, content analysis, relevance, psychosocial

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Authors: Jithin S. Kumar, Ramesh Kannan Kandasami

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Geomaterials are generally porous in nature due to the presence of discrete particles and interconnected voids. The porosity present in these geomaterials play a critical role in many engineering applications such as CO2 sequestration, well bore strengthening, enhanced oil and hydrocarbon recovery, hydraulic fracturing, and subsurface waste storage. These applications involves solid-fluid interactions, which govern the changes in the porosity which in turn affect the permeability and stiffness of the medium. Injecting fluid into the geomaterials results in permeation which exhibits small or negligible deformation of the soil skeleton followed by cavity expansion/ fingering/ fracturing (different forms of instabilities) due to the large deformation especially when the flow rate is greater than the ability of the medium to permeate the fluid. The complexity of this problem increases as the geomaterial behaves like a solid and fluid under certain conditions. Thus it is important to understand this multiphysics problem where in addition to the permeation, the elastic-plastic deformation of the soil skeleton plays a vital role during fluid injection. The phenomenon of permeation and cavity expansion in porous medium has been studied independently through extensive experimental and analytical/ numerical models. The analytical models generally use Darcy's/ diffusion equations to capture the fluid flow during permeation while elastic-plastic (Mohr-Coulomb and Modified Cam-Clay) models were used to predict the solid deformations. Hitherto, the research generally focused on modelling cavity expansion without considering the effect of injected fluid coming into the medium. Very few studies have considered the effect of injected fluid on the deformation of soil skeleton. However, the porosity changes during the fluid injection and coupled elastic-plastic deformation are not clearly understood. In this study, the phenomenon of permeation and instabilities such as cavity and finger/ fracture formation will be quantified extensively by performing experiments using a novel experimental setup in addition to utilizing image processing techniques. This experimental study will describe the fluid flow and soil deformation characteristics under different boundary conditions. Further, a well refined coupled semi-analytical model will be developed to capture the physics involved in quantifying the deformation behaviour of geomaterial during fluid injection.

Keywords: solid-fluid interaction, permeation, poroelasticity, plasticity, continuum model

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Authors: Kidane Workelul, Yohans Tekle, Guesh Negash, Haftay Abraha, Nigus Abebe Shumuye, Yisehak Tsegaye Redda

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Bovine papillomatosis (wart) is one of the economically important bovine skin diseases worldwide, caused by a group of viruses named papillomaviruses (PVs). However, it has often been misdiagnosed as other skin diseases and remained untreated. In order to determine the status of the diseases, twenty-two farms were visited, and fourteen infected cattle with cutaneous papillomatosis were identified from a total of 235. Papilloma biopsies were taken for molecular and histopathological characterization, the therapeutic trial of an autogenous vaccine was evaluated on infected animals. The overall status of bovine papillomatosis in this study was calculated as 5.96% (14/235). The disease was found to be statistically significant in the age groups less than two years (X² = 26.69, P = 0.0001). The more prominent histologically characterized lesions in the sampled tissue were identified as squamous papilloma and fibro-papilloma. The Polymerase Chain Reaction (PCR) based identification revealed that all the clinically and histo-pathologically characterized papillomatosis cases were found to be infected with Bovine Papilloma Virus1(BPV1), indicating that BPV1 was the most common and sole causative agent of the diseases in the study area. In immunizing active bovine papillomatosis, an autogenous vaccine therapeutic trial demonstrated excellent results, with practically full recovery and no recurrence of the infection. Hence, it is concluded that bovine papillomatosis is an economically important disease of young age group cattle as well as a treatable disease. So, the production of marketable autogenous vaccines against bovine papillomatosis should be started and given at an early stage.

Keywords: autogenous vaccine, bovine papillomatosis, bovine papilloma virus1 clinical-pathology, polymerase chine reaction, wart

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Authors: Javier De La Torre Costa, Belen Rubio Ballester, Martina Maier, Paul F. M. J. Verschure

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After a stroke, a great number of patients experience persistent motor impairments such as hemiparesis or weakness in one entire side of the body. As a result, the lack of use of the paretic limb might be one of the main contributors to functional loss after clinical discharge. We aim to reverse this cycle by promoting the use of the paretic limb during activities of daily living (ADLs). To do so, we describe the key components of a system that is composed of a wearable bracelet (i.e., a smartwatch) and a mobile phone, designed to bring a set of neurorehabilitation principles that promote acquisition, retention and generalization of skills to the home of the patient. A fundamental question is whether the loss in motor function derived from learned–non–use may emerge as a consequence of decision–making processes for motor optimization. Our system is based on well-established rehabilitation strategies that aim to reverse this behaviour by increasing the reward associated with action execution as well as implicitly reducing the expected cost associated with the use of the paretic limb, following the notion of the reinforcement–induced movement therapy (RIMT). Here we validate an accelerometer–based measure of arm use, and its capacity to discriminate different activities that require increasing movement of the arm. We also show how the system can act as a personalized assistant by providing specific goals and adjusting them depending on the performance of the patients. The usability and acceptance of the device as a rehabilitation tool is tested using a battery of self–reported and objective measurements obtained from acute/subacute patients and healthy controls. We believe that an extension of these technologies will allow for the deployment of unsupervised rehabilitation paradigms during and beyond the hospitalization time.

Keywords: stroke, wearables, learned non use, hemiparesis, ADLs

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Authors: Gleb Fomin, Kairat Tabynov, Nurkeldy Turebekov, Dinara Turegeldiyeva, Rinat Islamov

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The level of major cytokines in the blood of patients with COVID-19 varies greatly depending on age, gender, duration and severity of infection, and comorbidity. There are two clinically significant cytokines, IL-6 and TNF-α, which increase in levels in patients with severe COVID-19. However, in a model of COVID-19 in hamsters, TNF-α levels are unchanged or reduced, while the expression of other cytokines reflects the profile of cytokines found in patients’ plasma. The aim of our study was to evaluate the relationship between the level of cytokines in the blood, lungs, and lung damage in the model of the Syrian hamster (Mesocricetus auratus) infected with the SARS-CoV-2 strain. The study used outbred female and male Syrian hamsters (n=36, 4 groups) weighing 80-110 g and 5 months old (protocol IACUC, #4, 09/22/2020). Animals were infected intranasally with the hCoV-19/Kazakhstan/KazNAU-NSCEDI-481/2020 strain and euthanized at 3 d.p.i. The level of cytokines IL-6, TNF-α, IFN-α, and IFN-γ was determined by ELISA MyBioSourse (USA) for hamsters. Lung samples were subjected to histological processing. The presence of pathological changes in histological preparations was assessed on a 3-point scale. The work was carried out in the ABSL-3 laboratory. The data were analyzed in GraphPad Prism 6.00 (GraphPad Software, La Jolla, California, USA). The work was supported by the MES RK grant (AP09259865). In the blood, the level of TNF-α increased in males (p=0.0012) and IFN-γ in males and females (p=0.0001). On the contrary, IFN-α production decreased (p=0.0006). Only TNF-α level increased in lung tissues (p=0.0011). Correlation analysis showed a negative relationship between the level of IL-6 in the blood and lung damage in males (r -0.71, p=0.0001) and females (r-0.57, p=0.025). On the contrary, in males, the level of IL-6 in the lungs and score is positively correlated (r 0.80, p=0.01). The level of IFN-γ in the blood (r -0.64, p=0.035) and lungs (r-0.72, p=0.017) in males has a negative correlation with lung damage. No links were found for TNF-α and IFN-α. The study showed a positive association between lung injury and tissue levels of IL-6 in male hamsters. It is known that in humans, high concentrations of IL-6 in the lungs are associated with suppression of cellular immunity and, as a result, with an increase in the severity of COVID-19. TNF-α and IFN-γ play a key role in the pathogenesis of COVID-19 in hamsters. However, the mechanisms of their activity require more detailed study. IFN-α plays a lesser role in direct lung injury in a Syrian hamster model. We have shown the significance of tissue IL-6 and IFN-γ as predictors of the severity of lung damage in COVID-19 in the Syrian hamster model. Changes in the level of cytokines in the blood may not always reflect pathological processes in the lungs with COVID-19.

Keywords: syrian hamster, COVID-19, cytokines, biological model

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Authors: Alok Nahata

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Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.

Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone

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Authors: Abeer Ahmed Abdehameed

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Background: Diabetic sensorimotor polyneuropathy (DSP) is one of the most common micro vascular complications of type 2 diabetes. Loss of sensation is thought to contribute to lake of static and dynamic stability and increased risk of falling. Purpose: The purpose of this study was to compare the effects of low level laser (LLL) and monochromatic near infrared photo energy (MIRE) on pain , cutaneous sensation, static stability and index of lower limb blood flow in diabetic with peripheral neuropathy. Methods: Forty subjects with diabetic peripheral neuropathy were recruited for study. They were divided into two groups: The ( MIRE) group that included (20) patients and (LLL) group included (20) patients. All patients in the study had been subjected to various physical assessment procedures including pain, cutaneous sensation, Doppler flow meter and static stability assessments. The baseline measurements were followed by treatment sessions that conducted twice a week for 6 successive weeks. Results: The statistical analysis of the data had revealed significant improvement of the pain in both groups, with significant improvement in cutaneous sensation and static balance in (MIRE) group compared to (LLL) group; on the other hand results showed no significant differences on lower limb blood flow in both groups. Conclusion: Low level laser and monochromatic near infrared therapy can improve painful symptoms in patients with diabetic neuropathy. On the other hand (MIRE) is useful in improving cutaneous sensation and static stability in patients with diabetic neuropathy.

Keywords: diabetic neuropathy, doppler flow meter, low level laser, monochromatic near infrared photo energy

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Authors: Nathan Reeves

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Aim: The aim of this study was to evaluate if there was an impact on student learning when peer role play was substituted for a professional actor in the role of simulated patient in a simulation-based scenario. Method: Third-year exercise science students enrolled in a field project course in 2015 (n=24), and 2016 (n=20) participated in a simulation-based case scenario designed to develop their client-centred exercise prescription skills. During the simulation, students were provided with feedback from the simulated patients. In 2015, three professional actors played the part of the simulated patient, and in 2016 one of the simulated patients was a student from another exercise science cohort (peer role play). The student learning experience, consistency in case fidelity and feedback provided by the simulated patients was evaluated using a 5-point Likert scale survey and collecting phenomenological data. Results: Improvements to student pre and post confidence remained constant between the 2015 and 2016 cohorts (1.04 and 0.85). The perceived usefulness and enjoyability also remained high across the two cohorts (4.96 and 4.71). The feedback provided by all three simulated patients in 2016 was seen to strongly support student learning experience (4.82), and was of a consistent level (4.47). Significance of the findings to allied health: Simulation-based education is rapidly expanding in the curricula across the allied health professions. The simulated patient methodology continues to receive support as a pedagogy to develop a range of clinical skills including communication, engagement and client-centeredness. Upskilling students to peer role play can be a reasonable alternative to engaging paid actors.

Keywords: exercise science, simulation-based learning, simulated patient, peer role play

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Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

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Authors: Thinakar Mani Balusamy, Ratnakar S. Kini, Bharat Narasimhan, Venkateswaran A. R, Pugazhendi Thangavelu, Mohammed Ali, Prem Kumar K., Kani Sheikh M., Sibi Thooran Karmegam, Radhakrishnan N., Mohammed Noufal

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Introduction: Pancreatic injury remains a complicated condition requiring an individualized case by case approach to management. In this study, we aim to analyze the varied presentations and treatment outcomes of traumatic pancreatic injury in a tertiary care center. Methods: All consecutive patients hospitalized at our center with traumatic pancreatic injury between 2013 and 2017 were included. The American Association for Surgery of Trauma (AAST) classification was used to stratify patients into five grades of severity. Outcome parameters were then analyzed based on the treatment modality employed. Results: Of the 35 patients analyzed, 26 had an underlying blunt trauma with the remaining nine presenting due to penetrating injury. Overall in-hospital mortality was 28%. 19 of these patients underwent exploratory laparotomy with the remaining 16 managed nonoperatively. Nine patients had a severe injury ( > grade 3) – of which four underwent endotherapy, three had stents placed and one underwent an endoscopic pseudocyst drainage. Among those managed nonoperatively, three underwent a radiological drainage procedure. Conclusion: Mortality rates were clearly higher in patients managed operatively. This is likely a result of significantly higher degrees of major associated non-pancreatic injuries and not just a reflection of surgical morbidity. Despite this, surgical management remains the mainstay of therapy, especially in higher grades of pancreatic injury. However we would like to emphasize that endoscopic intervention definitely remains the preferred treatment modality when the clinical setting permits. This is especially applicable in cases of main pancreatic duct injury with ascites as well as pseudocysts.

Keywords: endotherapy, non-operative management, surgery, traumatic pancreatic injury

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Authors: Qiuyue Peng, Vladimir Zachar

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The application of adipose-derived stromal/stem cells (ASCs) in regenerative medicine is gaining more awareness due to their advanced translational potential and abundant source preparations. However, ASC-based translation has been confounded by high subpopulation heterogeneity, causing ambiguity about its precise therapeutic value. Some phenotypes defined by a unique combination of positive and negative surface markers have been found beneficial to the required roles. Therefore, the immunophenotypic repertoires of cultured ASCs and temporal changes of distinct subsets were investigated in this study. ASCs from three donors undergoing cosmetic liposuction were cultured in standard culturing methods, and the co-expression patterns based on the combination of selected markers at passages 1, 4, and 8 were analyzed by multi-chromatic flow cytometry. The results showed that the level of heterogeneity of subpopulations of ASCs became lower by in vitro expansion. After a few passages, most of the CD166⁺/CD274⁺/CD271⁺ based subpopulations converged to CD166 single positive cells. Meanwhile, these CD29⁺CD201⁺ double-positive cells, in combination with CD36/Stro-1 expression or without, feathered only the major epitopes and maintained prevailing throughout the whole process. This study suggested that, upon in vitro expansion, the phenotype repertoire of ASCs redistributed and stabilized in a way that cells co-expressing exclusively the strong markers remained dominant. These preliminary findings provide a general overview of the distribution of heterogeneous subsets residents within human ASCs during expansion in vitro. It is a critical step to fully characterize ASCs before clinical application, although the biological effects of heterogeneous subpopulations still need to be clarified.

Keywords: adipose-derived stromal/stem cells, heterogeneity, immunophenotype, subpopulations

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Authors: Helen K. Buteme, Rebecca Axelsson-Robertson, Moses L. Joloba, Henry W. Boom, Gunilla Kallenius, Markus Maeurer

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Background: The Ugandan population is heavily affected by infectious diseases and Human leukocyte antigen (HLA) diversity plays a crucial role in the host-pathogen interaction and affects the rates of disease acquisition and outcome. The identification of HLA class 1 alleles and determining which alleles are associated with tuberculosis (TB) outcomes would help in screening individuals in TB endemic areas for susceptibility to TB and to predict resistance or progression to TB which would inevitably lead to better clinical management of TB. Aims: To be able to determine the HLA class 1 phenotype distribution in a Ugandan TB cohort and to establish the relationship between these phenotypes and active and latent TB. Methods: Blood samples were drawn from 32 HIV negative individuals with active TB and 45 HIV negative individuals with latent MTB infection. DNA was extracted from the blood samples and the DNA samples HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. Results: HLA-A*02, A*01, A*74, A*30, B*15, B*58, C*07, C*03 and C*04 were the dominant phenotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the individuals with LTBI with only HLA-A*03 allele showing a statistically significant difference (p=0.0136). However, after FDR computation the corresponding q-value is above the expected proportion of false discoveries (q-value 0.2176). Key findings: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results also suggest that there may be a positive association between the HLA-A*03 allele and TB implying that individuals with the HLA-A*03 allele are at a higher risk of developing active TB.

Keywords: HLA, phenotype, tuberculosis, Uganda

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Authors: Angel Champion, Sadia Kanwal, Rafat Siddiqui

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Harnessing phytochemicals from plant sources presents a novel opportunity to prevent or treat malignant diseases, including breast cancer. Chemotherapy lacks precision in targeting cancerous cells while sparing normal cells, but a phytopharmaceutical approach may offer a solution. Dandelion, a common weed plant, is rich in phytochemicals and provides a safer, more cost-effective alternative with lower toxicity than traditional pharmaceuticals for conditions such as breast cancer. In this study, an in-vitro experiment will be conducted using the ethanol extract of Dandelion on triple-negative MDA-231 breast cancer cell lines. The polyphenolic analysis revealed that the Dandelion extract, particularly from the root and leaf (both cut and sifted), had the most potent antioxidant properties and exhibited the most potent antioxidation activity from the powdered leaf extract. The extract exhibits prospective promising effects for inducing cell proliferation and apoptosis in breast cancer cells, highlighting its potential for targeted therapeutic interventions. Standardizing methods for Dandelion use is crucial for future clinical applications in cancer treatment. Combining plant-derived compounds with cancer nanotechnology holds the potential for effective strategies in battling malignant diseases. Utilizing liposomes as carriers for phytoconstituent anti-cancer agents offers improved solubility, bioavailability, immunoregulatory effects, advancing anticancer immune function, and reducing toxicity. This integrated approach of natural products and nanotechnology has significant potential to revolutionize healthcare globally, especially in underserved communities where herbal medicine is prevalent.

Keywords: apoptosis, antioxidant activity, cancer nanotechnology, phytopharmaceutical

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Authors: S. M. Abdul Khader, Anurag Ayachit, Raghuvir Pai, K. A. Ahmed, V. R. K Rao, S. Ganesh Kamath

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The numerical simulation has made tremendous advances in investigating the blood flow phenomenon through elastic arteries. Such study can be useful in demonstrating the disease progression and haemodynamics of cardiovascular diseases such as atherosclerosis. In the present study, patient specific case diagnosed with partially stenosed complete right ICA and normal left carotid bifurcation without any atherosclerotic plaque formation is considered. 3D patient specific carotid bifurcation model is generated based on CT scan data using MIMICS-4.0 and numerical analysis is performed using FSI solver in ANSYS-14.5. The blood flow is assumed to be incompressible, homogenous and Newtonian, while the artery wall is assumed to be linearly elastic. The two-way sequentially-coupled transient FSI analysis is performed using FSI solver for three pulse cycles. The haemodynamic parameters such as flow pattern, Wall Shear Stress, pressure contours and arterial wall deformation are studied at the bifurcation and critical zones such as stenosis. The variation in flow behavior is studied throughout the pulse cycle. Also, the simulation results reveals that there is a considerable increase in the flow behavior in stenosed carotid in contrast to the normal carotid bifurcation system. The investigation also demonstrates the disturbed flow pattern especially at the bifurcation and stenosed zone elevating the haemodynamics, particularly during peak systole and later part of the pulse cycle. The results obtained agree well with the clinical observation and demonstrates the potential of patient specific numerical studies in prognosis of disease progression and plaque rupture.

Keywords: fluid-structure interaction, arterial stenosis, wall shear stress, carotid artery bifurcation

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Authors: Mubarack Ahmed, Gabriele Gradoni, Stephen C. Creagh, Gregor Tanner

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High-frequency cables commonly connect modern devices and sensors. Interestingly, the proportion of electric components is rising fast in an attempt to achieve lighter and greener devices. Modelling the propagation of signals through these cable networks in the presence of parameter uncertainty is a daunting task. In this work, we study the response of high-frequency cable networks using both Transmission Line and Quantum Graph (QG) theories. We have successfully compared the two theories in terms of reflection spectra using measurements on real, lossy cables. We have derived a generalisation of the vertex scattering matrix to include non-uniform networks – networks of cables with different characteristic impedances and propagation constants. The QG model implicitly takes into account the pseudo-chaotic behavior, at the vertices, of the propagating electric signal. We have successfully compared the asymptotic growth of eigenvalues of the Laplacian with the predictions of Weyl law. We investigate the nearest-neighbour level-spacing distribution of the resonances and compare our results with the predictions of Random Matrix Theory (RMT). To achieve this, we will compare our graphs with the generalisation of Wigner distribution for open systems. The problem of scattering from networks of cables can also provide an analogue model for wireless communication in highly reverberant environments. In this context, we provide a preliminary analysis of the statistics of communication capacity for communication across cable networks, whose eventual aim is to enable detailed laboratory testing of information transfer rates using software defined radio. We specialise this analysis in particular for the case of MIMO (Multiple-Input Multiple-Output) protocols. We have successfully validated our QG model with both TL model and laboratory measurements. The growth of Eigenvalues compares well with Weyl’s law and the level-spacing distribution agrees so well RMT predictions. The results we achieved in the MIMO application compares favourably with the prediction of a parallel on-going research (sponsored by NEMF21.)

Keywords: eigenvalues, multiple-input multiple-output, quantum graph, random matrix theory, transmission line

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Authors: Agnieszka A. Malinowska, R. Hejmanowski

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A number of European cities are strongly affected by ground movements caused by anthropogenic activities or post-anthropogenic metamorphosis. Those are mainly water pumping, current mining operation, the collapse of post-mining underground voids or mining-induced earthquakes. These activities lead to large and small-scale ground displacements and a ground ruptures. The ground movements occurring in urban areas could considerably affect stability and safety of structures and infrastructures. The complexity of the ground deformation phenomenon in relation to the structures and infrastructures vulnerability leads to considerable constraints in assessing the threat of those objects. However, the increase of access to the free software and satellite data could pave the way for developing new methods and strategies for environmental risk mitigation and management. Open source geographical information systems (OS GIS), may support data integration, management, and risk analysis. Lately, developed methods based on fuzzy logic and experts methods for buildings and infrastructure damage risk assessment could be integrated into OS GIS. Those methods were verified base on back analysis proving their accuracy. Moreover, those methods could be supported by ground displacement observation. Based on freely available data from European Space Agency and free software, ground deformation could be estimated. The main innovation presented in the paper is the application of open source software (OS GIS) for integration developed models and assessment of the threat of urban areas. Those approaches will be reinforced by analysis of ground movement based on free satellite data. Those data would support the verification of ground movement prediction models. Moreover, satellite data will enable our mapping of ground deformation in urbanized areas. Developed models and methods have been implemented in one of the urban areas hazarded by underground mining activity. Vulnerability maps supported by satellite ground movement observation would mitigate the hazards of land displacements in urban areas close to mines.

Keywords: fuzzy logic, open source geographic information science (OS GIS), risk assessment on urbanized areas, satellite interferometry (InSAR)

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Authors: Asma Omri, Noureddine Benothman, Sofiane Sayahi, Fethi Tlili, Hichem Besbes

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Cycling, a popular mode of transportation, can also be perilous due to cyclists' vulnerability to collisions with vehicles and obstacles. This paper presents an innovative cyclist safety system based on radar technology designed to offer real-time collision risk warnings to cyclists. The system incorporates a low-power radar sensor affixed to the bicycle and connected to a microcontroller. It leverages radar point cloud detections, a clustering algorithm, and a supervised classifier. These algorithms are optimized for efficiency to run on the TI’s AWR 1843 BOOST radar, utilizing a coarse classification approach distinguishing between cars, trucks, two-wheeled vehicles, and other objects. To enhance the performance of clustering techniques, we propose a 2-Level clustering approach. This approach builds on the state-of-the-art Density-based spatial clustering of applications with noise (DBSCAN). The objective is to first cluster objects based on their velocity, then refine the analysis by clustering based on position. The initial level identifies groups of objects with similar velocities and movement patterns. The subsequent level refines the analysis by considering the spatial distribution of these objects. The clusters obtained from the first level serve as input for the second level of clustering. Our proposed technique surpasses the classical DBSCAN algorithm in terms of geometrical metrics, including homogeneity, completeness, and V-score. Relevant cluster features are extracted and utilized to classify objects using an SVM classifier. Potential obstacles are identified based on their velocity and proximity to the cyclist. To optimize the system, we used the View of Delft dataset for hyperparameter selection and SVM classifier training. The system's performance was assessed using our collected dataset of radar point clouds synchronized with a camera on an Nvidia Jetson Nano board. The radar-based cyclist safety system is a practical solution that can be easily installed on any bicycle and connected to smartphones or other devices, offering real-time feedback and navigation assistance to cyclists. We conducted experiments to validate the system's feasibility, achieving an impressive 85% accuracy in the classification task. This system has the potential to significantly reduce the number of accidents involving cyclists and enhance their safety on the road.

Keywords: 2-level clustering, coarse classification, cyclist safety, warning system based on radar technology

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Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

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Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland（MASC）. Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63（a few，+）, CK7（+）, S100（+）, DOG1（-）, Ki67（MIB-1）（+，5%），pan-TRK（+）, PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

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Authors: Wania Mohammad Akram, Swetha Kannan, Urooj Shahid, Aisha Sajjad

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Ovarian ectopic pregnancy, a rare manifestation of ectopic gestation, involves the implantation of a fertilized egg on the ovarian surface. This condition poses diagnostic challenges and is associated with significant maternal morbidity if not promptly managed. This report presents the case of a 33-year-old nulliparous woman with a history of polycystic ovary syndrome (PCOS) undergoing ovulation induction therapy. Following her first conception in October 2021, she presented with symptoms of per vaginal spotting and low back pain, prompting a diagnosis of left adnexal ectopic pregnancy confirmed by transvaginal ultrasound and serum beta-human chorionic gonadotropin (B-HCG) levels. Medical management with methotrexate was initiated successfully. In August 2022, the patient conceived again, with subsequent ultrasound revealing a large pelvic collection suggestive of a complex ectopic pregnancy involving both ovaries. Despite initial stability, she developed abdominal pain necessitating emergency laparoscopy, which revealed an ovarian ectopic pregnancy with hemoperitoneum. Laparotomy was performed due to the complexity of the presentation, and histopathology confirmed viable chorionic villi within ovarian tissue. This case underscores the clinical management challenges posed by ovarian ectopic pregnancies, particularly in patients with previous ectopic pregnancies. The discussion reviews current literature on diagnostic modalities, treatment strategies, and outcomes associated with ovarian ectopic pregnancies, emphasizing the role of surgical intervention in cases refractory to conservative management. Tailored approaches considering individual patient factors are crucial to optimize outcomes and preserve fertility in such complex scenarios.

Keywords: obgyn, ovarian ectopic pregnancy, laproscopy, pcos

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Authors: Anamika A. Sharma, Arezou Ahmadi R. A., Narendra B. Parihar, Manjusha Sajith

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Introduction: Hemodialysis is the most effective therapeutic technique for patient with ESRD second to renal transplantation. However it is a lifelong therapy which requires frequent hospital, or dialysis centers visits mainly twice and thrice weekly, thus considerably changes the normal way of patient’s living. So this study aimed to Assess Health-Related Quality of life in End-Stage Renal Disease (ESRD) Undergoing Twice and Thrice weekly Hemodialysis. Method: A prospective observational, cross-sectional study was carried out from September 2016 to April 2017 in end-stage renal disease patients undergoing hemodialysis. Socio-demographic and clinical details of patients were obtained from the medical records. WHOQOL-BREF questionnaire was used to Access Health-Related Quality Of Life. Quality of Life scores of Twice weekly and Thrice weekly hemodialysis was analyzed by Kruskal Wallis Test. Results: Majority of respondents were male (72.55%), married (89.31%), employed (58.02%), belong to middle class (71.00%) and resides in rural area (58.78%). The mean ages in the patient undergoing twice weekly and thrice weekly hemodialysis were 51.89 ± 15.64 years and 51.33 ± 15.70 years respectively. Average Quality of Life scores observed in twice weekly and thrice weekly hemodialysis was 52.07 ± 13.30 (p=0.0037) and 52.87 ± 13.47 (p=0.0004) respectively. The hemoglobin of thrice weekly dialysis patients (10.28 gm/dL) was high as compared to twice weekly dialysis (9.23 gm/dL). Patients undergoing thrice weekly dialysis had improved serum urea, serum creatinine values (95.85 mg/dL, 8.32 mg/dL) as compared to twice weekly hemodialysis ( 104.94 mg/dL, 8.68 mg/dL). Conclusion: Our study concluded that there was no significant difference between overall Health-Related Quality Of Life in twice weekly and thrice weekly hemodialysis. Frequent hemodialysis was associated with improved control of hypertension, serum urea, serum creatinine levels.

Keywords: end stage renal disease, health related quality of life, twice weekly hemodialysis, thrice weekly hemodialysis

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Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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Authors: Ivana Čavlina Tomašević, Višnjica Vučetić, Maja Telišman Prtenjak, Barbara Malečić

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The Split wildfire on the mid-Adriatic Coast in July 2017 is one of the most severe wildfires in Croatian history, given the size and unexpected fire behavior, and it is used in this research as a case study to run the Weather Research and Forecasting Spread Fire (WRF SFIRE) model. This coupled fire-atmosphere model was successfully run for the first time ever for one Croatian wildfire case. Verification of coupled simulations was possible by using the detailed reconstruction of the Split wildfire. Specifically, precise information on ignition time and location, together with mapped fire progressions and spotting within the first 30 hours of the wildfire, was used for both – to initialize simulations and to evaluate the model’s ability to simulate fire’s propagation and final fire scar. The preliminary simulations were obtained using high-resolution vegetation and topography data for the fire area, additionally interpolated to fire grid spacing at 33.3 m. The results demonstrated that the WRF SFIRE model has the ability to work with real data from Croatia and produce adequate results for forecasting fire spread. As the model in its setup has the ability to include and exclude the energy fluxes between the fire and the atmosphere, this was used to investigate possible fire-atmosphere interactions during the Split wildfire. Finally, successfully coupled simulations provided the first numerical evidence that a wildfire from the Adriatic coast region can modify the dynamical structure of the surrounding atmosphere, which agrees with observations from fire grounds. This study has demonstrated that the WRF SFIRE model has the potential for operational application in Croatia with more accurate fire predictions in the future, which could be accomplished by inserting the higher-resolution input data into the model without interpolation. Possible uses for fire management in Croatia include prediction of fire spread and intensity that may vary under changing weather conditions, available fuels and topography, planning effective and safe deployment of ground and aerial firefighting forces, preventing wildland-urban interface fires, effective planning of evacuation routes etc. In addition, the WRF SFIRE model results from this research demonstrated that the model is important for fire weather research and education purposes in order to better understand this hazardous phenomenon that occurs in Croatia.

Keywords: meteorology, agrometeorology, fire weather, wildfires, couple fire-atmosphere model

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Authors: Hany Elsaid Fawaz Abdallah

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This study presents a new artificial neural network(ANN) model to predict the Nusselt Number and pressure drop for the turbulent flow in a triangular corrugated plate heat exchanger for forced air and turbulent water flow. An experimental investigation was performed to create a new dataset for the Nusselt Number and pressure drop values in the following range of dimensionless parameters: The plate corrugation angles (from 0° to 60°), the Reynolds number (from 10000 to 40000), pitch to height ratio (from 1 to 4), and Prandtl number (from 0.7 to 200). Based on the ANN performance graph, the three-layer structure with {12-8-6} hidden neurons has been chosen. The training procedure includes back-propagation with the biases and weight adjustment, the evaluation of the loss function for the training and validation dataset and feed-forward propagation of the input parameters. The linear function was used at the output layer as the activation function, while for the hidden layers, the rectified linear unit activation function was utilized. In order to accelerate the ANN training, the loss function minimization may be achieved by the adaptive moment estimation algorithm (ADAM). The ‘‘MinMax’’ normalization approach was utilized to avoid the increase in the training time due to drastic differences in the loss function gradients with respect to the values of weights. Since the test dataset is not being used for the ANN training, a cross-validation technique is applied to the ANN network using the new data. Such procedure was repeated until loss function convergence was achieved or for 4000 epochs with a batch size of 200 points. The program code was written in Python 3.0 using open-source ANN libraries such as Scikit learn, TensorFlow and Keras libraries. The mean average percent error values of 9.4% for the Nusselt number and 8.2% for pressure drop for the ANN model have been achieved. Therefore, higher accuracy compared to the generalized correlations was achieved. The performance validation of the obtained model was based on a comparison of predicted data with the experimental results yielding excellent accuracy.

Keywords: artificial neural networks, corrugated channel, heat transfer enhancement, Nusselt number, pressure drop, generalized correlations

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Authors: Francesca Favero, Despina Learmonth

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Carbohydrate addiction is said to be the sustained dependence on hyperpalatable foods rich in carbohydrates and sugar. This addiction manifests in increased consumption of carbohydrates through binging: a behaviour typically associated with eating disorders. There is a lack of consensus amongst relevant experts as to whether carbohydrates are physiologically or psychologically addictive. With an increased focus on carbohydrate addiction, an outpatient treatment programme, HELP, has been established in Cape Town, South Africa, to specifically address this issue. This research aimed to explore, pre-and post-intervention, the possible presence of, and subsequent shifts in, the maintaining mechanisms identified in the transdiagnostic model for eating disorders. However, the potential for the emergence of other perpetuating factors was not discounted and the nature of the analysis allowed for this possibility. Eight women between the ages of twenty-two and fifty, who had completed the outpatient treatment programme in the last six months, were interviewed. They were asked to speak retrospectively about their personal difficulties, eating and food, and their experience of the treatment. Thematic analysis was employed to identify themes arising from the data. Five themes congruent with the transdiagnostic model’s factors emerged: over-evaluation of weight and shape, core low self-esteem, interpersonal difficulties, clinical perfectionism and mood intolerance. A variety of sub-themes, elaborating upon the various ways in which the disordered eating was maintained, also emerged from the data. Shifts in these maintaining mechanisms were identified. Although not necessarily indicative of recovery, the results suggest that the outpatient HELP programme had a positive overall influence on the participants; and that the transdiagnostic model may be useful in understanding and guiding the treatment of clients who engage in this type of treatment programme.

Keywords: eating disorders, binge eating disorder, carbohydrate addiction, transdiagnostic model, maintaining mechanisms, thematic analysis, outpatient treatment

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Authors: Leslie M. Gutman

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Conduct problems (CP) represent a major dilemma, with wide-ranging and long-lasting individual and societal impacts. Children experience heterogeneous patterns of conduct problems; based on the age of onset, developmental course and related risk factors from around age 3. Early childhood represents a potential window for intervention efforts aimed at changing the trajectory of early starting conduct problems. Using the UK Millennium Cohort Study (n = 17,206 children), this study (a) identifies trajectories of conduct problems from ages 3 to 14 years and (b) assesses the cumulative and interactive effects of individual, family and socioeconomic risk factors from ages 9 months to 14 years. The same factors according to three domains were assessed, including child (i.e., low verbal ability, hyperactivity/inattention, peer problems, emotional problems), family (i.e., single families, parental poor physical and mental health, large family size) and socioeconomic (i.e., low family income, low parental education, unemployment, social housing). A cumulative risk score for the child, family, and socioeconomic domains at each age was calculated. It was then examined how the cumulative risk scores explain variation in the trajectories of conduct problems. Lastly, interactive effects among the different domains of cumulative risk were tested. Using group-based trajectory modeling, four distinct trajectories were found including a ‘low’ problem group and three groups showing childhood-onset conduct problems: ‘school-age onset’; ‘early-onset, desisting’; and ‘early-onset, persisting’. The ‘low’ group (57% of the sample) showed a low probability of conducts problems, close to zero, from 3 to 14 years. The ‘early-onset, desisting’ group (23% of the sample) demonstrated a moderate probability of CP in early childhood, with a decline from 3 to 5 years and a low probability thereafter. The ‘early-onset, persistent’ group (8%) followed a high probability of conduct problems, which declined from 11 years but was close to 70% at 14 years. In the ‘school-age onset’ group, 12% of the sample showed a moderate probability of conduct problems from 3 and 5 years, with a sharp increase by 7 years, increasing to 50% at 14 years. In terms of individual risk, all factors increased the likelihood of being in the childhood-onset groups compared to the ‘low’ group. For cumulative risk, the socioeconomic domain at 9 months and 3 years, the family domain at all ages except 14 years and child domain at all ages were found to differentiate childhood-onset groups from the ‘low’ group. Cumulative risk at 9 months and 3 years did not differentiate between the ‘school-onset’ group and ‘low’ group. Significant interactions were found between the domains for the ‘early-onset, desisting group’ suggesting that low levels of risk in one domain may buffer the effects of high risk in another domain. The implications of these findings for preventive interventions will be highlighted.

Keywords: conduct problems, cumulative risk, developmental trajectories, early childhood, adolescence

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Amira ben Hassine, A. Valverde, V. Serafín, C. Muñoz-San Martín, M. Garranzo-Asensio, M. Gamella, R. Barderas, M. Pedrero, N. Raouafi, S. Campuzano, P. Yáñez-Sedeño, J. M. Pingarrón

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This work describes the development of a dual electrochemical immunosensing platform for accurate determination of two target proteins, IL-13 Receptor α2 (IL-13Rα2) and E-cadherin (E-cad). The proposed methodology is based on the use of sandwich immunosensing approaches (involving horseradish peroxidase-labeled detector antibodies) implemented onto magnetic microbeads (MBs) and amperometric transduction at screen-printed dual carbon electrodes (SPdCEs). The magnetic bioconjugates were captured onto SPdCEs and the amperometric transduction was performed using the H2O2/hydroquinone (HQ) system. Under optimal experimental conditions, the developed bio platform demonstrates linear concentration ranges of 1.0–25 and 5.0-100 ng mL-1, detection limits of 0.28 and 1.04 ng mL-1 for E-cad and IL-13Rα2, respectively, and excellent selectivity against other non-target proteins. The developed immuno-platform also offers a good reproducibility among amperometric responses provided by nine different sensors constructed in the same manner (Relative Standard Deviation values of 3.1% for E-cad and 4.3% for IL-13Rα2). Moreover, obtained results confirm the practical applicability of this bio-platform for the accurate determination of the endogenous levels of both extracellular receptors in colon cancer cells (both intact and lysed) with different metastatic potential and serum and tissues from patients diagnosed with colorectal cancer at different grades. Interesting features in terms of, simplicity, speed, portability and sample amount required to provide quantitative results, make this immuno-platform more compatible than conventional methodologies with the clinical diagnosis and prognosis at the point of care.

Keywords: electrochemistry, mmunosensors, biosensors, E-cadherin, IL-13 receptor α2, cancer colorectal

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Athicha Cherdpunt, Patompong Satapornpong

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The medical cannabis is made up of components also known as cannabinoids, which consists of two ingredients which are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Interestingly, the Cannabinoid can be used for many treatments such as chemotherapy, including nausea and vomiting, cachexia, anorexia nervosa, spinal cord injury and disease, epilepsy, pain, and many others. However, the adverse drug reactions (ADRs) of THC can cause sedation, anxiety, dizziness, appetite stimulation and impairments in driving and cognitive function. Furthermore, genetic polymorphisms of CYP2C9, CYP2C19 and CYP3A4 influenced the THC metabolism and might be a cause of ADRs. Particularly, CYP2C19*17 allele increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (UM). The aim of this study, is to investigate the frequency of CYP2C19*17 alleles in Thai patients who have been treated with medical cannabis. We prospectively enrolled 60 Thai patients who were treated with medical cannabis and clinical data from College of Pharmacy, Rangsit University. DNA of each patient was isolated from EDTA blood, using the Genomic DNA Mini Kit. CYP2C19*17 genotyping was conducted using the real time-PCR ViiA7 (ABI, Foster City, CA, USA). 30 patients with medical cannabis-induced ADRs group, 20 (67%) were female, and 10 (33%) were male, with an age range of 30-69 years. On the other hand, 30 patients without medical cannabis-induced ADRs (control group) consist of 17 (57%) female and 13 (43%) male. The most ADRs for medical cannabis treatment in the case group were dry mouth and dry throat (77%), tachycardia (70%), nausea (30%) and arrhythmia(10%). Accordingly, the case group carried CYP2C19*1/*1 (normal metabolizer) approximately 93%, while 7% patients carrying CYP2C19*1/*17 (ultra rapid metabolizers) exhibited in this group. Meanwhile, we found 90% of CYP2C19*1/*1 and 10% of CYP2C19*1/*17 in control group. In this study, we identified the frequency of CYP2C19*17 allele in Thai population which will support the pharmacogenetics biomarkers for screening and avoid ADRs of medical cannabis treatment.

Keywords: CYP2C19, allele frequency, ultra rapid metabolizer, medical cannabis

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Authors: Li Yin, Xiaoqin Wang

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Background and purpose: Cancer diagnosis is part of a complex stochastic process, in which patients' personal and social characteristics influence the choice of diagnosing methods, diagnosing methods, in turn, influence the initial assessment of cancer stage, the initial assessment, in turn, influences the choice of treating methods, and treating methods in turn influence cancer outcomes such as cancer survival. To evaluate diagnosing methods, one needs to estimate and test the causal effect of a regime of cancer diagnosis and treatments. Recently, Wang and Yin (Annals of statistics, 2020) derived a new general formula, which expresses these causal effects in terms of the point effects of treatments in single-point causal inference. As a result, it is possible to estimate and test these causal effects via point effects. The purpose of the work is to estimate and test causal effects under various regimes of cancer diagnosis and treatments via point effects. Challenges and solutions: The cancer stage has influences from earlier diagnosis as well as on subsequent treatments. As a consequence, it is highly difficult to estimate and test the causal effects via standard parameters, that is, the conditional survival given all stationary covariates, diagnosing methods, cancer stage and prognosis factors, treating methods. Instead of standard parameters, we use the point effects of cancer diagnosis and treatments to estimate and test causal effects under various regimes of cancer diagnosis and treatments. We are able to use familiar methods in the framework of single-point causal inference to accomplish the task. Achievements: we have applied this method to stomach cancer survival from a clinical study in Sweden. We have studied causal effects under various regimes, including the optimal regime of diagnosis and treatments and the effect moderation of the causal effect by age and gender.

Keywords: cancer diagnosis, causal effect, point effect, G-formula, sequential causal effect

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