20 results on '"Ali H. Alghamdi"'
Search Results
2. Advancing brain tumor detection: harnessing the Swin Transformer’s power for accurate classification and performance analysis
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Abdullah A. Asiri, Ahmad Shaf, Tariq Ali, Muhammad Ahmad Pasha, Aiza Khan, Muhammad Irfan, Saeed Alqahtani, Ahmad Alghamdi, Ali H. Alghamdi, Abdullah Fahad A. Alshamrani, Magbool Alelyani, and Sultan Alamri
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Brain ,Tumor ,Medical image analysis ,Computational intelligence ,Transformer ,Swin transformer ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
The accurate detection of brain tumors through medical imaging is paramount for precise diagnoses and effective treatment strategies. In this study, we introduce an innovative and robust methodology that capitalizes on the transformative potential of the Swin Transformer architecture for meticulous brain tumor image classification. Our approach handles the classification of brain tumors across four distinct categories: glioma, meningioma, non-tumor, and pituitary, leveraging a dataset comprising 2,870 images. Employing the Swin Transformer architecture, our method intricately integrates a multifaceted pipeline encompassing sophisticated preprocessing, intricate feature extraction mechanisms, and a highly nuanced classification framework. Utilizing 21 matrices for performance evaluation across all four classes, these matrices provide a detailed insight into the model’s behavior throughout the learning process, furthermore showcasing a graphical representation of confusion matrix, training and validation loss and accuracy. The standout performance parameter, accuracy, stands at an impressive 97%. This achievement outperforms established models like CNN, DCNN, ViT, and their variants in brain tumor classification. Our methodology’s robustness and exceptional accuracy showcase its potential as a pioneering model in this domain, promising substantial advancements in accurate tumor identification and classification, thereby contributing significantly to the landscape of medical image analysis.
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- 2024
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3. Enhancing Brain Tumor Diagnosis: Transitioning From Convolutional Neural Network to Involutional Neural Network
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Abdullah A. Asiri, Ahmad Shaf, Tariq Ali, Maryam Zafar, Muhammad Ahmad Pasha, Muhammad Irfan, Saeed Alqahtani, Ahmad Joman Alghamdi, Ali H. Alghamdi, Abdullah Fahad A. Alshamrani, Maqbool Aleylyani, and Sultan Alamri
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Involutional ,convolutional ,parameters ,brain ,tumor ,image classification ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
] Accurate classification of brain tumors is essential for effective medical diagnosis and treatment planning. Traditional approaches rely on convolutional neural networks (CNNs) for tumor detection, but they often suffer from high computational demands due to the large number of parameters. In this paper, we propose a novel approach for brain tumor classification using involutional neural networks (InvNets), which are designed to mitigate the parameter-intensive nature of CNNs. Unlike the spatial-agnostic and channel-specific convolution kernel, the involution kernel is location-specific and channel-agnostic. This location-specific operation allows the network to adapt to various visual patterns with respect to different spatial locations, enhancing its ability to capture intricate features within the medical images. Our study focuses on a four-class brain tumor classification problem, aiming to differentiate between different tumor types based on medical imaging data. In a comparative analysis, we demonstrate that conventional CNNs require over 4 million parameters, whereas our proposed InvNets require less than 0.2 million parameters, making them more efficient and resource-friendly. The evaluation of both CNNs and InvNets is carried out using standard performance matrices: accuracy, precision, recall, F1 score, and AUC-ROC values. Our findings reveal that the InvNets consistently outperform traditional CNNs. The InvNet architecture achieves an impressive 92% accuracy rate, showcasing its potential for accurate brain tumor classification. This improved accuracy, combined with the reduced parameter count, highlights the effectiveness of InvNets for medical image analysis tasks, especially in scenarios with limited computational resources.
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- 2023
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4. Next-Gen brain tumor classification: pioneering with deep learning and fine-tuned conditional generative adversarial networks
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Abdullah A. Asiri, Muhammad Aamir, Tariq Ali, Ahmad Shaf, Muhammad Irfan, Khlood M. Mehdar, Samar M. Alqhtani, Ali H. Alghamdi, Abdullah Fahad A. Alshamrani, and Osama M. Alshehri
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Brain tumor ,Conditional generative adversarial network ,Discriminator model ,Generator model ,Tumor classification ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Brain tumor has become one of the fatal causes of death worldwide in recent years, affecting many individuals annually and resulting in loss of lives. Brain tumors are characterized by the abnormal or irregular growth of brain tissues that can spread to nearby tissues and eventually throughout the brain. Although several traditional machine learning and deep learning techniques have been developed for detecting and classifying brain tumors, they do not always provide an accurate and timely diagnosis. This study proposes a conditional generative adversarial network (CGAN) that leverages the fine-tuning of a convolutional neural network (CNN) to achieve more precise detection of brain tumors. The CGAN comprises two parts, a generator and a discriminator, whose outputs are used as inputs for fine-tuning the CNN model. The publicly available dataset of brain tumor MRI images on Kaggle was used to conduct experiments for Datasets 1 and 2. Statistical values such as precision, specificity, sensitivity, F1-score, and accuracy were used to evaluate the results. Compared to existing techniques, our proposed CGAN model achieved an accuracy value of 0.93 for Dataset 1 and 0.97 for Dataset 2.
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- 2023
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5. Multi-target potential of Indian phytochemicals against SARS-CoV-2: A docking, molecular dynamics and MM-GBSA approach extended to Omicron B.1.1.529.
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Jency Roshni, R. Vaishali, KS Ganesh, N. Dharani, Khalid J. Alzahrani, Hamsa Jameel Banjer, Ali H. Alghamdi, Abdulrahman Theyab, Shiek SSJ Ahmed, and Shankargouda Patil
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Phytochemicals ,Drug-likeness ,SARS-CoV-2 ,COVID-19 ,Arbidol ,Favipiravir ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Background: SARS-CoV-2, an emerged strain of corona virus family became almost serious health concern worldwide. Despite vaccines availability, reports suggest the occurrence of SARS-CoV-2 infection even in a vaccinated population. With frequent evolution and expected multiple COVID-19 waves, improved preventive, diagnostic, and treatment measures are required. In recent times, phytochemicals have gained attention due to their therapeutic characteristics and are suggested as alternative and complementary treatments for infectious diseases. This present study aimed to identify potential inhibitors against reported protein targets of SARS-CoV-2. Methodology: We computationally investigated potential SARS-CoV-2 protein targets from the literature and collected druggable phytochemicals from Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Further, we implemented a systematic workflow of molecular docking, dynamic simulations and generalized born surface area free-energy calculations (MM-GBSA). Results: Extensive literature search and assessment of 1508 articles identifies 13 potential SARS-CoV-2 protein targets. We screened 501 druggable phytochemicals with proven biological activities. Analysis of 6513(501 *13) docked phytochemicals complex, 26 were efficient against SARS-CoV-2. Amongst, 4,8-dihydroxysesamin and arboreal from Gmelina arborea were ranked potential against most of the targets with binding energy ranging between − 10.7 to − 8.2 kcal/mol. Additionally, comparative docking with known drugs such as arbidol (−6.6 to −5.1 kcal/mol), favipiravir (−5.5 to −4.5 kcal/mol), hydroxychloroquine (−6.5 to −5.1 kcal/mol), and remedesivir (−8.0 to −5.3 kcal/mol) revealed equal/less affinity than 4,8-dihydroxysesamin and arboreal. Interestingly, the nucleocapsid target was found commonly inhibited by 4,8-dihydroxysesamin and arboreal. Molecular dynamic simulation and Molecular mechanics generalized born surface area (MM-GBSA)calculations reflect that both the compounds possess high inhibiting potential against SARS-CoV-2 including the recently emerged Omicron variant (B.1.1.529). Conclusion: Overall our study imparts the usage of phytochemicals as antiviral agents for SARS-CoV-2 infection. Additional in vitro and in vivo testing of these phytochemicals is required to confirm their potency.
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- 2022
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6. Advancing Brain Tumor Classification through Fine-Tuned Vision Transformers: A Comparative Study of Pre-Trained Models
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Abdullah A. Asiri, Ahmad Shaf, Tariq Ali, Muhammad Ahmad Pasha, Muhammad Aamir, Muhammad Irfan, Saeed Alqahtani, Ahmad Joman Alghamdi, Ali H. Alghamdi, Abdullah Fahad A. Alshamrani, Magbool Alelyani, and Sultan Alamri
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brain tumor classification ,pre-trained ViT ,fine-tuning ,medical image analysis ,cutting-edge models ,Chemical technology ,TP1-1185 - Abstract
This paper presents a comprehensive study on the classification of brain tumor images using five pre-trained vision transformer (ViT) models, namely R50-ViT-l16, ViT-l16, ViT-l32, ViT-b16, and ViT-b32, employing a fine-tuning approach. The objective of this study is to advance the state-of-the-art in brain tumor classification by harnessing the power of these advanced models. The dataset utilized for experimentation consists of a total of 4855 images in the training set and 857 images in the testing set, encompassing four distinct tumor classes. The performance evaluation of each model is conducted through an extensive analysis encompassing precision, recall, F1-score, accuracy, and confusion matrix metrics. Among the models assessed, ViT-b32 demonstrates exceptional performance, achieving a high accuracy of 98.24% in accurately classifying brain tumor images. Notably, the obtained results outperform existing methodologies, showcasing the efficacy of the proposed approach. The contributions of this research extend beyond conventional methods, as it not only employs cutting-edge ViT models but also surpasses the performance of existing approaches for brain tumor image classification. This study not only demonstrates the potential of ViT models in medical image analysis but also provides a benchmark for future research in the field of brain tumor classification.
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- 2023
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7. Modulatory effect of dietary probiotic and prebiotic supplementation on growth, immuno-biochemical alterations, DNA damage, and pathological changes in E. coli-infected broiler chicks
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Mohamed A. Hashem, Azza E. A. Hassan, Hala M. M. Abou-Elnaga, Walied Abdo, Naief Dahran, Ali H. Alghamdi, and Ehab Kotb Elmahallawy
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modulatory ,probiotic ,prebiotic ,immuno-biochemical alteration ,DNA ,histopathological ,Veterinary medicine ,SF600-1100 - Abstract
Avian pathogenic Escherichia coli is one of the principal causes of heavy economic losses to the poultry industry. Little is known about the underlying mechanisms, particularly the potential role of immunoglobulin A and the DNA damage, involving the beneficial effects of dietary supplementation of probiotics and prebiotics in avian colibacillosis. The current study investigated the potential effects of probiotic and prebiotic dietary supplementation on E. coli-infected broiler chicks. A total of 120 1-day-old unsexed Hubbard chicks were divided into six groups: Group 1 was considered as a negative control; Group 2 was supplemented with 1 g/kg feed of Lactobacillus plantarum; Group 3 was supplemented with amylase enzyme; Group 4 served as a positive control infected orally by E. coli O78; Group 5 was supplemented with L. plantarum from 1-day-old chicken and then infected orally with E. coli O78; and Group 6 was supplemented with amylase enzyme from 1-day old chicken and then infected orally with E. coli O78. For all examined groups, the experimental period lasted for 42 days. The E. coli-infected group revealed a decrease in body performance parameters with a significant increase in the liver enzymes and renal function tests. The same group recorded a significant decrease in serum total proteins, albumins, and globulins, and the alteration of immunological parameters, antioxidant enzymes, oxidative stress parameters, and comet assay revealed highly damaged DNA in the liver and the intestine. By histopathological examination, a series of histopathological changes in the liver, the kidney, and the intestine were observed. The infected chick pretreated with probiotics or prebiotics demonstrated an improvement in body performance parameters besides a significant decrease in the hepatic enzymes and renal function tests. We noticed that, in treated groups, there was a significant increase in serum total proteins in the serum albumin and globulin levels, immunological parameters, and antioxidant enzymes. Furthermore, DNA damage and histopathological changes within hepatic, renal, and intestinal tissues were markedly diminished in the treated groups compared with the infected group. We concluded that the adverse effects of E. coli could be modulated through the chemopreventive administration of probiotics and prebiotics.
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- 2022
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8. Exploring the Power of Deep Learning: Fine-Tuned Vision Transformer for Accurate and Efficient Brain Tumor Detection in MRI Scans
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Abdullah A. Asiri, Ahmad Shaf, Tariq Ali, Unza Shakeel, Muhammad Irfan, Khlood M. Mehdar, Hanan Talal Halawani, Ali H. Alghamdi, Abdullah Fahad A. Alshamrani, and Samar M. Alqhtani
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brain tumor ,vision transformer ,healthcare ,diagnosis ,Medicine (General) ,R5-920 - Abstract
A brain tumor is a significant health concern that directly or indirectly affects thousands of people worldwide. The early and accurate detection of brain tumors is vital to the successful treatment of brain tumors and the improved quality of life of the patient. There are several imaging techniques used for brain tumor detection. Among these techniques, the most common are MRI and CT scans. To overcome the limitations associated with these traditional techniques, computer-aided analysis of brain images has gained attention in recent years as a promising approach for accurate and reliable brain tumor detection. In this study, we proposed a fine-tuned vision transformer model that uses advanced image processing and deep learning techniques to accurately identify the presence of brain tumors in the input data images. The proposed model FT-ViT involves several stages, including the processing of data, patch processing, concatenation, feature selection and learning, and fine tuning. Upon training the model on the CE-MRI dataset containing 5712 brain tumor images, the model could accurately identify the tumors. The FT-Vit model achieved an accuracy of 98.13%. The proposed method offers high accuracy and can significantly reduce the workload of radiologists, making it a practical approach in medical science. However, further research can be conducted to diagnose more complex and rare types of tumors with more accuracy and reliability.
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- 2023
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9. Brain Tumor Detection and Classification Using Fine-Tuned CNN with ResNet50 and U-Net Model: A Study on TCGA-LGG and TCIA Dataset for MRI Applications
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Abdullah A. Asiri, Ahmad Shaf, Tariq Ali, Muhammad Aamir, Muhammad Irfan, Saeed Alqahtani, Khlood M. Mehdar, Hanan Talal Halawani, Ali H. Alghamdi, Abdullah Fahad A. Alshamrani, and Samar M. Alqhtani
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brain tumor ,U-Net ,ResNet50 ,CNN ,segmentation ,Science - Abstract
Nowadays, brain tumors have become a leading cause of mortality worldwide. The brain cells in the tumor grow abnormally and badly affect the surrounding brain cells. These cells could be either cancerous or non-cancerous types, and their symptoms can vary depending on their location, size, and type. Due to its complex and varying structure, detecting and classifying the brain tumor accurately at the initial stages to avoid maximum death loss is challenging. This research proposes an improved fine-tuned model based on CNN with ResNet50 and U-Net to solve this problem. This model works on the publicly available dataset known as TCGA-LGG and TCIA. The dataset consists of 120 patients. The proposed CNN and fine-tuned ResNet50 model are used to detect and classify the tumor or no-tumor images. Furthermore, the U-Net model is integrated for the segmentation of the tumor regions correctly. The model performance evaluation metrics are accuracy, intersection over union, dice similarity coefficient, and similarity index. The results from fine-tuned ResNet50 model are IoU: 0.91, DSC: 0.95, SI: 0.95. In contrast, U-Net with ResNet50 outperforms all other models and correctly classified and segmented the tumor region.
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- 2023
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10. Tamoxifen Increased Parasite Burden and Induced a Series of Histopathological and Immunohistochemical Changes During Chronic Toxoplasmosis in Experimentally Infected Mice
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Ashraf Mohamed Barakat, Hassan Ali Mohamed El Fadaly, Rabab Fawzy Selem, Abd El-Nasser A. Madboli, Khaled A. Abd El-Razik, Ehssan Ahmed Hassan, Ali H. Alghamdi, and Ehab Kotb Elmahallawy
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chronic toxoplasmosis ,tamoxifen ,histopathology ,immunohistochemistry ,real-time PCR ,Microbiology ,QR1-502 - Abstract
The global distribution of breast cancer and the opportunistic nature of the parasite have resulted in many patients with breast cancer becoming infected with toxoplasmosis. However, very limited information is available about the potential effects of tamoxifen on chronic toxoplasmosis and its contribution to the reactivation of the latent infection. The present study investigated the potential effects of tamoxifen on chronic toxoplasmosis in animal models (Swiss albino mice). Following induction of chronic toxoplasmosis and treatment with the drug for 14 and 28 days, the anti-parasitic effects of tamoxifen were evaluated by parasitological assessment and counting of Toxoplasma cysts. In addition, the effects of the drug on the parasite load were evaluated and quantitated using TaqMan real-time quantitative PCR followed by investigation of the major histopathological changes and immunohistochemical findings. Interestingly, tamoxifen increased the parasite burden on animals treated with the drug during 14 and 28 days as compared with the control group. The quantification of the DNA concentrations of Toxoplasma P29 gene after the treatment with the drug revealed a higher parasite load in both treated groups vs. control groups. Furthermore, treatment with tamoxifen induced a series of histopathological and immunohistochemical changes in the kidney, liver, brain, and uterus, revealing the exacerbating effect of tamoxifen against chronic toxoplasmosis. These changes were represented by the presence of multiple T. gondii tissue cysts in the lumen of proximal convoluted tubules associated with complete necrosis in their lining epithelium of the kidney section. Meanwhile, liver tissue revealed multiple T. gondii tissue cysts in hepatic parenchyma which altered the structure of hepatocytes. Moreover, clusters of intracellular tachyzoites were observed in the lining epithelium of endometrium associated with severe endometrial necrosis and appeared as diffuse nuclear pyknosis combined with sever mononuclear cellular infiltration. Brain tissues experienced the presence of hemorrhages in pia mater and multiple T. gondii tissue cysts in brain tissue. The severity of the lesions was maximized by increasing the duration of treatment. Collectively, the study concluded novel findings in relation to the potential role of tamoxifen during chronic toxoplasmosis. These findings are very important for combating the disease, particularly in immunocompromised patients which could be life-threatening.
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- 2022
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11. Antitrypanosomal and Antileishmanial Activity of Chalcones and Flavanones from Polygonum salicifolium
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Ahmed M. Zheoat, Samya Alenezi, Ehab Kotb Elmahallawy, Marzuq A. Ungogo, Ali H. Alghamdi, David G. Watson, John O. Igoli, Alexander I. Gray, Harry P. de Koning, and Valerie A. Ferro
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Polygonum salicifolium ,chalcone ,flavanone ,Leishmania mexicana ,Trypanosoma brucei brucei ,Trypanosoma congolense ,Medicine - Abstract
Trypanosomiasis and leishmaniasis are a group of neglected parasitic diseases caused by several species of parasites belonging to the family Trypansomatida. The present study investigated the antitrypanosomal and antileishmanial activity of chalcones and flavanones from Polygonum salicifolium, which grows in the wetlands of Iraq. The phytochemical evaluation of the plant yielded two chalcones, 2′,4′-dimethoxy-6′-hydroxychalcone and 2′,5′-dimethoxy-4′,6′-dihydroxychalcone, and two flavanones, 5,7-dimethoxyflavanone and 5,8-dimethoxy-7-hydroxyflavanone. The chalcones showed a good antitrypanosomal and antileishmanial activity while the flavanones were inactive. The EC50 values for 2′,4′-dimethoxy-6′-hydroxychalcone against Trypanosoma brucei brucei (0.5 μg/mL), T. congolense (2.5 μg/mL), and Leishmania mexicana (5.2 μg/mL) indicated it was the most active of the compounds. None of the compounds displayed any toxicity against a human cell line, even at 100 µg/mL, or cross-resistance with first line clinical trypanocides, such as diamidines and melaminophenyl arsenicals. Taken together, our study provides significant data in relation to the activity of chalcones and flavanones from P. salicifolium against both parasites in vitro. Further future research is suggested in order to investigate the mode of action of the extracted chalcones against the parasites.
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- 2021
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12. Cloning and functional complementation of ten Schistosoma mansoni phosphodiesterases expressed in the mammalian host stages.
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Jane C Munday, Stefan Kunz, Titilola D Kalejaiye, Marco Siderius, Susanne Schroeder, Daniel Paape, Ali H Alghamdi, Zainab Abbasi, Sheng Xiang Huang, Anne-Marie Donachie, Samia William, Abdel Nasser Sabra, Geert Jan Sterk, Sanaa S Botros, David G Brown, Charles S Hoffman, Rob Leurs, and Harry P de Koning
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Only a single drug against schistosomiasis is currently available and new drug development is urgently required but very few drug targets have been validated and characterised. However, regulatory systems including cyclic nucleotide metabolism are emerging as primary candidates for drug discovery. Here, we report the cloning of ten cyclic nucleotide phosphodiesterase (PDE) genes of S. mansoni, out of a total of 11 identified in its genome. We classify these PDEs by homology to human PDEs. Male worms displayed higher expression levels for all PDEs, in mature and juvenile worms, and schistosomula. Several functional complementation approaches were used to characterise these genes. We constructed a Trypanosoma brucei cell line in which expression of a cAMP-degrading PDE complements the deletion of TbrPDEB1/B2. Inhibitor screens of these cells expressing only either SmPDE4A, TbrPDEB1 or TbrPDEB2, identified highly potent inhibitors of the S. mansoni enzyme that elevated the cellular cAMP concentration. We further expressed most of the cloned SmPDEs in two pde1Δ/pde2Δ strains of Saccharomyces cerevisiae and some also in a specialised strain of Schizosacharomyces pombe. Five PDEs, SmPDE1, SmPDE4A, SmPDE8, SmPDE9A and SmPDE11 successfully complemented the S. cerevisiae strains, and SmPDE7var also complemented to a lesser degree, in liquid culture. SmPDE4A, SmPDE8 and SmPDE11 were further assessed in S. pombe for hydrolysis of cAMP and cGMP; SmPDE11 displayed considerable preferrence for cGMP over cAMP. These results and tools enable the pursuit of a rigorous drug discovery program based on inhibitors of S. mansoni PDEs.
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- 2020
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13. Incidence and Risk Factors of Infections Among Diffuse Large B-cell Lymphoma and Classical Hodgkin’s Lymphoma Patients in a Tertiary Care Center in Saudi Arabia: A Retrospective Cohort Study
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Rakan H Alelyani, Ali H Alghamdi, Thamer A Almughamisi, Abdulrahman M Alshareef, Abdulaziz N Kadasa, Amir M Alrajhi, Abdullah K Alburayk, Ahmed S Barefah, Osman O Radhwi, Abdullah T Almohammadi, Salem M Bahashawan, and Hatem M AlAhwal
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General Engineering - Published
- 2023
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14. Prevalence of Mask-Associated Dry Eye (Made) Among the General Population of Al-Baha Area, Saudi Arabia
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Ali H Alghamdi, Mahadi A Bashir, Saleha K Alatawi, Hani A Alghamdi, and Ahmed M Alzahrani
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Background:During the coronavirus disease 2019 (COVID-19) pandemic, the utilization of face masks was made mandatory as a protective tool. However, prolonged use of face masks increases the risk of dry eye, which affects people's visual-based activities. The Al-Baha area is a high-altitude area located in the west of the Kingdom of Saudi Arabia in the Hejaz region. As a result, residents of this region are more likely to suffer from dry eyes because of the extreme environmental conditions. Subsequently, the aim of this study is to determine the prevalence of mask-associated dry eye (MADE) and its associated risk factors among the general population of the Al-Baha area, Saudi Arabia. Materials and Methods:This is a cross-sectional study conducted using an anonymous online questionnaire composed of 56 questions. Data were collected from 480 participants in the Al-Baha area. Results:Theprevalence of MADE among the general population of Al-Baha, Saudi Arabia, was 39.2%, which is higher than the global prevalence. The risk factors for MADE include exposure to dry weather, wind, blepharitis, and ectropion. Moreover, it was determined that females were more likely to develop MADE than males; likewise, people in the age group of 16 to 25 were more likely to have MADE. Conclusion:The study shows that the prevalence of MADE in Al-Baha is comparatively higher than the worldwide prevalence, which is best explained by this area being at a high altitude. Based on the study's findings, some recommendations to guard against MADE are made to patients, the general public, and ophthalmologists. 
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- 2023
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15. Differences in Transporters Rather than Drug Targets Are the Principal Determinants of the Different Innate Sensitivities of
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Marzuq A, Ungogo, Gustavo D, Campagnaro, Ali H, Alghamdi, Manal J, Natto, and Harry P, de Koning
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Trypanosoma ,Trypanosoma congolense ,Animals ,Membrane Transport Proteins ,Suramin ,Trypanocidal Agents ,Arsenicals ,Pentamidine - Abstract
The animal trypanosomiases are infections in a wide range of (domesticated) animals with any species of African trypanosome, such as
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- 2022
16. Impact of COVID-19 Pandemic Lockdown on the Prognosis, Morbidity, and Mortality of Patients Undergoing Elective and Emergency Abdominal Surgery: A Retrospective Cohort Study in a Tertiary Center, Saudi Arabia
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Rakan H. Alelyani, Ali H. Alghamdi, Saad M. Mahrous, Bader M. Alamri, Mudhawi H. Alhiniah, Maisa S. Abduh, and Saleh M. Aldaqal
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SARS-CoV-2 ,Health, Toxicology and Mutagenesis ,Communicable Disease Control ,Public Health, Environmental and Occupational Health ,Humans ,COVID-19 ,abdominal surgery ,Saudi Arabia ,Pandemics ,Retrospective Studies - Abstract
The SARS-CoV-2 pandemic’s main concerns are limiting the spread of infectious diseases and upgrading the delivery of health services, infrastructure, and therapeutic provision. The goal of this retrospective cohort study was to evaluate the emergency experience and delay of elective abdominal surgical intervention at King Abdul-Aziz University Hospital from October 2019 to October 2020, with a focus on post-operative morbidity and mortality before and during the COVID-19 pandemic. This study compares two groups of patients with emergent and elective abdominal surgical procedures between two different periods; the population was divided into two groups: the control group, which included 403 surgical patients, and the lockdown group, which included 253 surgical patients. During the lockdown, surgical activity was reduced by 37.2% (p = 0.014), and patients were more likely to require reoperations and blood transfusions during or after surgery (p= 0.002, 0.021, and 0.018, respectively). During the lockdown period, the average length of stay increased from 3.43 to 5.83 days (p = 0.002), and the patients who developed complications (53.9%) were more than those in the control period (46.1%) (p = 0.001). Our tertiary teaching hospital observed a significant decline in the overall number of surgeries performed during the COVID-19 pandemic and lockdown period. During the lockdown, abdominal surgery was performed only on four patients; they were positive for COVID-19. Three of them underwent exploratory laparotomy; two of the three developed shock post-operative; one patient had colon cancer (ASA score 3), one had colon disease (ASA score 2), and two had perforated bowels (ASA scores 2 and 4, respectively). Two out of four deaths occurred after surgery. Our results showed the impact of the COVID-19 lockdown on surgical care as both 30-day mortality and total morbidity have risen considerably.
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- 2022
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17. Author response: Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei
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Anna Dimitriou, Daniel Paape, Christopher M Woodley, Ulrich Zachariae, Anthonius A. Eze, Simone Weyand, Ibrahim A. Teka, Ali H. Alghamdi, Richard R. Tidwell, Arvind Kumar, Jane C. Munday, Juan F. Quintana, Mark Carrington, Mohammed I. Al-Salabi, Paul M. O'Neill, Laura F Anderson, Maria Esther Martin Abril, Harry P. de Koning, Teresa Sprenger, Hasan M. S. Ibrahim, Fredrik Svensson, Simon Gudin, Fabian Hulpia, Patrik Milic, Chinyere E Okpara, Gustavo D. Campagnaro, Dominik Gurvic, Graeme Smart, David W. Boykin, Christophe Dardonville, Luca Settimo, Siu Pui Ying Kelly, Laura Watson, Joanna Wielinska, and Mark C. Field
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Biochemistry ,biology ,Chemistry ,medicine ,Trypanosoma brucei ,biology.organism_classification ,Pentamidine ,medicine.drug - Published
- 2020
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18. Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei
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Harry P. de Koning, Ibrahim A. Teka, Hasan M. S. Ibrahim, Christopher M Woodley, Simon Gudin, Patrik Mili, Arvind Kumar, Daniel Paape, Fredrik Svensson, Fabian Hulpia, Jane C. Munday, Mark Carrington, Mohammed I. Al-Salabi, Dominik Gurvic, Laura F Anderson, Christophe Dardonville, David W. Boykin, Chinyere E Okpara, Ali H. Alghamdi, Luca Settimo, Laura Watson, Maria Esther Martin Abril, Joanna Wielinska, Gustavo D. Campagnaro, Graeme Smart, Ulrich Zachariae, Anthonius A. Eze, Richard R. Tidwell, Anna Dimitriou, Siu Pui Ying Kelly, and Paul M. O'Neill
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Membrane potential ,chemistry.chemical_classification ,biology ,Chemistry ,Aquaporin ,Melarsoprol ,Trypanosoma brucei ,Permeation ,biology.organism_classification ,Amino acid ,Aquaporin 2 ,medicine ,Biophysics ,medicine.drug ,Pentamidine - Abstract
Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2’s unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant but exclude most other diamidine drugs. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family.
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- 2020
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19. Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei
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Paul M. O'Neill, Harry P. de Koning, Anna Dimitriou, Ulrich Zachariae, Joanna Wielinska, Arvind Kumar, Anthonius A. Eze, Mark C. Field, Chinyere E Okpara, Juan F. Quintana, Richard R. Tidwell, Simone Weyand, Luca Settimo, Siu Pui Ying Kelly, Christopher M Woodley, Dominik Gurvic, Ibrahim A. Teka, Mohammed I. Al-Salabi, Fredrik Svensson, Fabian Hulpia, Ali H. Alghamdi, Patrik Milic, Teresa Sprenger, Hasan M. S. Ibrahim, David W. Boykin, Laura Watson, Laura F Anderson, Daniel Paape, Mark Carrington, Maria Esther Martin Abril, Simon Gudin, Gustavo D. Campagnaro, Graeme Smart, Jane C. Munday, Christophe Dardonville, Campagnaro, Gustavo Daniel [0000-0001-6542-0485], Hulpia, Fabian [0000-0002-7470-3484], Eze, Anthonius A [0000-0002-4821-1689], Carrington, Mark [0000-0002-6435-7266], De Koning, Harry P [0000-0002-9963-1827], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,melarsoprol ,Melarsoprol ,CROSS-RESISTANCE ,DIAMIDINE DRUGS ,DIMINAZENE ACETURATE ,SUBSTRATE RECOGNITION MOTIFS ,ADENOSINE TRANSPORTER ,AQUAGLYCEROPORIN 2 ,Medicine and Health Sciences ,BLOOD-STREAM FORMS ,Trypanosoma brucei ,Biology (General) ,NUCLEOSIDE TRANSPORTER ,chemistry.chemical_classification ,Microbiology and Infectious Disease ,biology ,Chemistry ,General Neuroscience ,General Medicine ,Permeation ,Trypanocidal Agents ,3. Good health ,Amino acid ,Aquaporin 2 ,Medicine ,medicine.drug ,Research Article ,drug transport ,QH301-705.5 ,Science ,infectious disease ,030106 microbiology ,Trypanosoma brucei brucei ,Chemical biology ,Aquaporin ,chemical biology ,Genetics and Molecular Biology ,Aquaporins ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Biochemistry and Chemical Biology ,pentamidine ,parasitic diseases ,medicine ,biochemistry ,Animals ,DRUG-RESISTANCE ,drug resistance ,General Immunology and Microbiology ,microbiology ,biology.organism_classification ,HIGH-AFFINITY TRANSPORTER ,aquaporin ,030104 developmental biology ,Trypanosomiasis, African ,Mutation ,General Biochemistry ,Biophysics ,Other ,Pentamidine - Abstract
Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2's unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant although most other diamidine drugs are excluded. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family. African sleeping sickness is a potentially deadly illness caused by the parasite Trypanosoma brucei. The disease is treatable, but many of the current treatments are old and are becoming increasingly ineffective. For instance, resistance is growing against pentamidine, a drug used in the early stages in the disease, as well as against melarsoprol, which is deployed when the infection has progressed to the brain. Usually, cases resistant to pentamidine are also resistant to melarsoprol, but it is still unclear why, as the drugs are chemically unrelated. Studies have shown that changes in a water channel called aquaglyceroporin 2 (TbAQP2) contribute to drug resistance in African sleeping sickness; this suggests that it plays a role in allowing drugs to kill the parasite. This molecular 'drain pipe' extends through the surface of T. brucei, and should allow only water and a molecule called glycerol in and out of the cell. In particular, the channel should be too narrow to allow pentamidine or melarsoprol to pass through. One possibility is that, in T. brucei, the TbAQP2 channel is abnormally wide compared to other members of its family. Alternatively, pentamidine and melarsoprol may only bind to TbAQP2, and then 'hitch a ride' when the protein is taken into the parasite as part of the natural cycle of surface protein replacement. Alghamdi et al. aimed to tease out these hypotheses. Computer models of the structure of the protein were paired with engineered changes in the key areas of the channel to show that, in T. brucei, TbAQP2 provides a much broader gateway into the cell than observed for similar proteins. In addition, genetic analysis showed that this version of TbAQP2 has been actively selected for during the evolution process of T. brucei. This suggests that the parasite somehow benefits from this wider aquaglyceroporin variant. This is a new resistance mechanism, and it is possible that aquaglyceroporins are also larger than expected in other infectious microbes. The work by Alghamdi et al. therefore provides insight into how other germs may become resistant to drugs., This work was supported by the UK Medical Research Council (MRC) [grant G0701258 to HPdK] andby the US National Institutes of Health (NIH) [Grant No. GM111749 to DWB]. DC was supported byan MRC iCASE award [MR/R015791/1]. UZ acknowledges funding from the Scottish UniversitiesPhysics Alliance. AHA is funded through a PhD studentship from Albaha University, Saudi Arabia.GDC was funded by a PhD Studentship from Science Without Borders [206385/2014–5, CNPq,Brazil]. TS was funded via a Doctoral Training Programme of the MRC and the Cambridge Trust andSW was funded by a Sir Henry Dale fellowship of the Wellcome Trust and Royal Society. The authorsthank Dr Tansy Hammarton for the use of the CRK2 RNAi cell line and Prof David Horn for the use ofthe aqp1-3 null cell line. This work was supported by a grant from the Wellcome Trust (204697/Z/16/Z to MCF. The authors are grateful to Professor George Diallinas, University of Athens, Greece, forhis exceptionally insightful reviewer comments and have adopted several of his arguments inrevision.
- Published
- 2020
20. Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei
- Author
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Ali H Alghamdi, Jane C Munday, Gustavo Daniel Campagnaro, Dominik Gurvic, Fredrik Svensson, Chinyere E Okpara, Arvind Kumar, Juan Quintana, Maria Esther Martin Abril, Patrik Milić, Laura Watson, Daniel Paape, Luca Settimo, Anna Dimitriou, Joanna Wielinska, Graeme Smart, Laura F Anderson, Christopher M Woodley, Siu Pui Ying Kelly, Hasan MS Ibrahim, Fabian Hulpia, Mohammed I Al-Salabi, Anthonius A Eze, Teresa Sprenger, Ibrahim A Teka, Simon Gudin, Simone Weyand, Mark Field, Christophe Dardonville, Richard R Tidwell, Mark Carrington, Paul O'Neill, David W Boykin, Ulrich Zachariae, and Harry P De Koning
- Subjects
Trypanosoma brucei ,aquaporin ,drug transport ,pentamidine ,drug resistance ,melarsoprol ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2’s unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant although most other diamidine drugs are excluded. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family.
- Published
- 2020
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