158 results on '"Ahmed SU"'
Search Results
2. Inflammatory Status As a Predictor of Perioperative Risk in Patients Undergoing Non-Cardiac Vascular Surgery.
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Ahmed SU, Fisher M, and Ahmed MS
- Abstract
Introduction: Patients scheduled to undergo vascular surgery represent a significant population at risk of major adverse cardiac events (MACE's) post operation. This is due to a number of inflammatory mechanisms, designed to aid in post surgical recovery. A number of screening tools have been designed such as the EAGLE risk score or the Goldman and Detsky scores, to aid in identification of at-risk individuals. Recently inflammatory biomarkers have been suggested as a tool to aid in this assessment. The role of interleukins such as IL-1 and Il-6 have particularly been of interest to current research. Our hypothesis aims to test whether there is any benefit to measuring inflammatory biomarkers post operation as a tool to identify individuals at risk of MACEs., Method: We identified 75 eligible patients scheduled to undergo vascular surgery (bypass, EVAR or open AAA repair or endarterectomy) and measured four inflammatory biomarkers (IL-1, IL-6, ICAM-1 & CRP) pre and post operatively on days 1-4 to identify correlations and identify differences in individuals who had a MACE vs those that didn't. A MACE was defined by a rise in T troponin of 0.06 or greater or ECG changes agreed upon by two clinicians or a stroke RESULTS: Of the 75 patients, 13 were identified to have a MACE. The result showed that both IL-1 and ICAM show a significantly positive correlation between pre and post operative levels with ICAM-1 significantly positive on all 4 days and IL-1 significantly positive on days 1, 3 & 4. When comparing the significant difference in change in inflammatory biomarkers between the MACE group and non-MACE group, a significant difference was only noted in the ICAM biomarker. ICAM was significantly different between the two groups on day 1 and day 2 (t test value 0.0455 and 0.0492 respectively) but was non-significant on days 3 and 4. All other biomarkers showed no significant difference pre and post op., Discussion: Overall, it is suggestable that measuring inflammatory biomarkers in vascular surgery patients is a valuable aid to clinicians in potentially identifying at-risk groups and should be used as an adjunct to already existing mechanisms available to the clinician., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)
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- 2024
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3. Evaluation of Primary and Recurrent Breast Cancer after Giving Adjuvant Therapy in Correlation with the Receptor Status.
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Azad SA, Rahman MS, Bhuiyan AKM, Islam MJ, Ahmed SU, and Hossain AFM
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- Humans, Female, Middle Aged, Adult, Chemotherapy, Adjuvant, Aged, Breast Neoplasms pathology, Breast Neoplasms therapy, Breast Neoplasms metabolism, Breast Neoplasms drug therapy, Neoplasm Recurrence, Local, Receptors, Progesterone metabolism, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism
- Abstract
Breast cancer is the most common type of cancer among women. The molecular subtypes of breast cancer, depending on the Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status, usually play a vital role for the adjuvant treatment. Interestingly, there is a good possibility of change of receptor status in the recurrence of same primary tumor. The study is designed April 2018 to March 2019 to see the concordance in triple-receptor expression (ER, PR, and HER-2) between the primary and the locally recurrent breast cancer patient and the results can be able to influence the management and prognosis of the breast cancer patients. This observational study was carried out in the department of surgical oncology, NICRH where total 48 patients were studied who were subjected to core biopsy of recurrent lesion for ER, PR and HER-2 status. A structured case record form was used to interview and collect data. Data analysis was done using SPSS version 26.0 to see concordance and discordance in triple-receptor expression between the primary and the locally recurrent breast cancer patient. Among 48 cases, 12(25.0%), 10(20.83%) and 2(4.16%) patients showed Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (Her-2) discordance that are statistically significant in every receptor status. Majority discordance of ER, PR and Her-2 were associated with invasive duct cell carcinoma (IDC); ER & Her-2 discordance was equally associated with histological grade 2 and 3 whereas PR discordance had significant association with grade 3. Staging of disease showed that all ER, PR and Her-2 discordance were associated with stage (p<0.05). Besides, majority discordance was mostly associated with lumpectomy except Her-2 discordance. Besides, among the adjuvant treatment regimen chemotherapy along with radiotherapy was mostly associated with discordance of all receptors (p<0.05). Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status of primary breast cancer showed 25.0%, 20.83% and 4.16% discordant in recurrent episodes in this study. Invasive duct cell carcinoma, histological grade 2 and 3, stage II, stage III, MRM and CT along with RT are major attributable factors in this study.
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- 2024
4. Pattern of ENT Diseases in Children: A Peripheral Military Hospital Based Study.
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Sumon MAK, Ahmed SU, Afsana SD, Hasan MS, Islam MS, and Rahman MM
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- Humans, Child, Male, Female, Adolescent, Child, Preschool, Infant, Bangladesh epidemiology, Prevalence, Infant, Newborn, Tonsillitis epidemiology, Hospitals, Military statistics & numerical data, Otorhinolaryngologic Diseases epidemiology
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This study was aimed to find out the hospital based prevalence of paediatric ENT disorders in an ENT OPD of a peripheral military hospital of Bangladesh Armed Forces. This observational study was carried out at ENT out patient department of CMH Momenshahi, from 1st April 2017 to 31st March 2020. Irrespective of age and sex a total of 4612 children, between the ages of 0-14 years were included in this study. All types of ENT disorders were taken in to account. Data were obtained after ENT examination and necessary investigations. Total 4612 cases were studied. Male children (52.2%) were affected more and most of the children belongs the 6-10 years age group (44.4%).Throat related disorder (40.7%) were predominant followed by ear (34.8%). The most common ENT disorders were Chronic Tonsillitis (21.8%) followed by acute otitis media (16.1%) and pharyngitis (9.8%). Rate of Chronic otitis media (COM) was only 46(1%). ENT diseases are one of the major health problems among children. In addition to improved health education, socioeconomic status and better access to health care facilities; provision of early ENT specialist consultation may significantly reduce chronic or recurring symptoms and long term morbidities of common ENT disorders in children.
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- 2024
5. Vitamin B6 Pathway Maintains Glioblastoma Cell Survival in 3D Spheroid Cultures.
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Moosa NY, Azeem SA, Lodge JK, Cheung W, and Ahmed SU
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- Humans, Cell Line, Tumor, Signal Transduction, Cell Culture Techniques methods, Tumor Microenvironment, Metabolomics methods, Glioblastoma metabolism, Glioblastoma pathology, Vitamin B 6 metabolism, Vitamin B 6 pharmacology, Spheroids, Cellular metabolism, Spheroids, Cellular pathology, Spheroids, Cellular drug effects, Cell Survival drug effects, Brain Neoplasms metabolism, Brain Neoplasms pathology
- Abstract
Glioblastoma (GBM) is a deadly brain cancer. The prognosis of GBM patients has marginally improved over the last three decades. The response of GBMs to initial treatment is inevitably followed by relapse. Thus, there is an urgent need to identify and develop new therapeutics to target this cancer and improve both patient outcomes and long-term survival. Metabolic reprogramming is considered one of the hallmarks of cancers. However, cell-based studies fail to accurately recapitulate the in vivo tumour microenvironment that influences metabolic signalling and rewiring. Against this backdrop, we conducted global, untargeted metabolomics analysis of the G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical cell culture conditions. Our studies revealed that the levels of multiple metabolites associated with the vitamin B6 pathway were significantly altered in 3D spheroids compared to the 2D monolayer cultures. Importantly, we show that pharmacological intervention with hydralazine, a small molecule that reduces vitamin B6 levels, resulted in the cell death of 3D GBM spheroid cultures. Thus, our study shows that inhibition of the vitamin B6 pathway is a novel therapeutic strategy for the development of targeted therapies in GBMs.
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- 2024
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6. Embolization techniques of spontaneous direct carotid-cavernous fistulae: a single-center experience.
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Lindgren A, Ahmed SU, Bodani V, Chung E, Agid R, Barazarte HA, Nicholson PJ, Schaafsma JD, Radovanovic I, Terbrugge K, Mosimann PR, Krings T, and Hendriks EJ
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- Humans, Female, Male, Aged, Retrospective Studies, Middle Aged, Adult, Angiography, Digital Subtraction, Treatment Outcome, Aged, 80 and over, Cerebral Angiography, Magnetic Resonance Imaging, Carotid-Cavernous Sinus Fistula therapy, Carotid-Cavernous Sinus Fistula diagnostic imaging, Embolization, Therapeutic methods
- Abstract
Purpose: Spontaneous direct carotid-cavernous fistula (CCF) are usually caused by a ruptured carotid cavernous aneurysm. We studied treatment of spontaneous direct CCFs in a single-center cohort of a high-volume tertiary referral center, reporting anatomical details, technical approaches of treatment, and outcomes., Methods: Adult patients with a spontaneous direct CCF treated between 2010-2022 with follow-up MRI and/or DSA imaging available were retrospectively analyzed. We studied age, sex, clinical presentation, angiographic findings, treatment techniques, outcomes, and complications., Results: Out of 80 patients with CCFs, twelve patients were treated for a non-traumatic direct CCF (15%) in 13 sessions. Median age was 65 years. Two patients had an underlying connective tissue disorder. In 10 cases, the direct CCF was caused by a ruptured cavernous carotid aneurysm. The direct CCFs were treated by endovascular transarterial embolization (10 cases), transvenous embolization (1 case), or surgery (1 case). Selective closure of the shunt was possible in 10 patients. Two patients were treated with parent vessel occlusion (PVO; one endovascular; one surgical, with bypass). Complications occurred in 2 / 12 patients (17%), with permanent morbidity in two patients (17%): trigeminal neuralgia after PVO and new infarct after surgical PVO and bypass. Selective closure of CCF resulted in no morbidity. There was no mortality in our series., Conclusion: Spontaneous direct CCFs are caused by rupture of a cavernous carotid aneurysm in most cases. Selective closure of the shunt, usually feasible transarterially with coils, achieves good results. Reconstructive endovascular techniques are preferred to minimize treatment related neurological complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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7. EEG workload estimation and classification: a systematic review.
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Hassan J, Reza MS, Ahmed SU, Anik NH, and Khan MO
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Objective: Electroencephalography (EEG) has evolved into an indispensable instrument for estimating cognitive workload in various domains. ML and DL techniques have been increasingly employed to develop accurate workload estimation and classification models based on EEG data. The goal of this systematic review is to compile the body of research on EEG workload estimation and classification using ML and DL approaches., Methods: The PRISMA procedures were followed in conducting the review, searches were conducted through databases at SpringerLink, ACM Digital Library, IEEE Explore, PUBMED, and Science Direct from the beginning to the end of February 16, 2024. Studies were selected based on predefined inclusion criteria. Data were extracted to capture study design, participant demographics, EEG features, ML/DL algorithms, and reported performance metrics., Results: Out of the 125 items that emerged, 33 scientific papers were fully evaluated. The study designs, participant demographics, and EEG workload measurement and categorization techniques used in the investigations differed. SVM, CNN, and hybrid networks are examples of ML and DL approaches that were often used. Analyzing the accuracy scores achieved by different ML/DL models. Furthermore, a relationship was noted between sample frequency and model accuracy, with higher sample frequencies generally leading to improved performance. The percentage distribution of ML/DL methods revealed that SVMs, CNNs, and RNNs were the most commonly utilized techniques, reflecting their robustness in handling EEG data., Significance: The comprehensive review emphasizes how ML may be used to identify mental workload across a variety of disciplines using EEG data. Optimizing practical applications requires multimodal data integration, standardization efforts, and real-world validation studies. These systems will also be further improved by addressing ethical issues and investigating new EEG properties, which will improve human-computer interaction and performance assessment., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)
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- 2024
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8. Dataset of cattle biometrics through muzzle images.
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Ahmed SU, Frnda J, Waqas M, and Khan MH
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The Cattle Biometrics Dataset is the result of a rigorous process of data collecting, encompassing a wide range of cattle photographs obtained from publicly accessible cattle markets and farms. The dataset provided contains a comprehensive collection of more than 8,000 annotated samples derived from several cow breeds. This dataset represents a valuable asset for conducting research in the field of biometric recognition. The diversity of cattle in this context includes a range of ages, genders, breeds, and environmental conditions. Every photograph is taken from different quality cameras is thoroughly annotated, with special attention given to the muzzle of the cattle, which is considered an excellent biometric characteristic. In addition to its obvious practical benefits, this dataset possesses significant potential for extensive reuse. Within the domain of computer vision, it serves as a catalyst for algorithmic advancements, whereas in the agricultural sector, it augments practises related to cattle management. Machine learning aficionados highly value the use of machine learning for the construction and experimentation of models, especially in the context of transfer learning. Interdisciplinary collaboration is actively encouraged, facilitating the advancement of knowledge at the intersections of agriculture, computer science, and data science. The Cattle Biometrics Dataset represents a valuable resource that has the potential to stimulate significant advancements in various academic disciplines, fostering ground breaking research and innovation., (© 2024 The Author(s).)
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- 2024
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9. Knowledge and attitudes of patient safety attendants in managing hospitalized older adults with delirium and dementia.
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Ahmed SU, Cayea D, Tackett S, Bellantoni M, Massare J, Ward H, Schoenborn N, and Oh ES
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- Humans, Aged, Patient Safety, Allied Health Personnel, Delirium therapy, Dementia therapy
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- 2024
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10. Transarterial Embolization of Dural Arteriovenous Fistulas: Conventional, Pressure Cooker, and Microballoon Catheter Embolization Techniques.
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Lindgren A, Ahmed SU, Bodani V, Andrade Barazarte H, Agid R, Kee TP, Nicholson P, Hendriks EJ, and Krings T
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Background and Objectives: Dural fistulas are abnormal connections between dural arteries and intracranial veins treated mainly endovascularly in most settings. The aim was to examine a single-institution experience of microballoon catheter transarterial embolization (TAE) of dural arteriovenous fistulas (dAVFs) and compare it with other TAE techniques., Methods: We retrospectively identified all dAVFs treated at our institution between 2017 and 2022 with microballoon, conventional, and pressure cooker TAE. We studied occlusion and retreatment rates, treatment-related complications, and radiation doses., Results: During the study period, 66 patients underwent 75 TAE procedures to treat 68 dAVFs: 47 conventional TAE, 14 pressure cooker TAE, and 14 microballoon TAE. Median age of the study population was 63 years with 32% females. The most common dAVF location was the transverse sinus and 20% of dAVFs presented with hemorrhage. At 3-month follow-up, stable complete occlusion of the dAVF was seen in 72% (n = 34) after conventional TAE, 79% (n = 11) after pressure cooker TAE, and 86% (n = 12) after microballoon TAE. Retreatment was required in 19% (n = 9) after conventional TAE, 7% (n = 1) after pressure cooker TAE, and 7% (n = 1) after microballoon TAE. Treatment-related complications occurred in 17% (n =) after conventional TAE, 29% (n = 4) after pressure cooker TAE, and 7% (n = 1) after microballoon TAE., Conclusion: In our experience, microballoon TAE of dAVFs resulted in better initial and 3-month angiographic outcomes and required less retreatment than conventional TAE. Microballoon TAE also resulted in fewer treatment-related complications than other techniques. In our experience, microballoon TAE is a reliable and safe endovascular technique to treat dAVFs., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)
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- 2024
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11. A novel and innovative cancer classification framework through a consecutive utilization of hybrid feature selection.
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Mahto R, Ahmed SU, Rahman RU, Aziz RM, Roy P, Mallik S, Li A, and Shah MA
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- Humans, Microarray Analysis, Genetic Techniques, Machine Learning, Algorithms, Neoplasms genetics
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Cancer prediction in the early stage is a topic of major interest in medicine since it allows accurate and efficient actions for successful medical treatments of cancer. Mostly cancer datasets contain various gene expression levels as features with less samples, so firstly there is a need to eliminate similar features to permit faster convergence rate of classification algorithms. These features (genes) enable us to identify cancer disease, choose the best prescription to prevent cancer and discover deviations amid different techniques. To resolve this problem, we proposed a hybrid novel technique CSSMO-based gene selection for cancer classification. First, we made alteration of the fitness of spider monkey optimization (SMO) with cuckoo search algorithm (CSA) algorithm viz., CSSMO for feature selection, which helps to combine the benefit of both metaheuristic algorithms to discover a subset of genes which helps to predict a cancer disease in early stage. Further, to enhance the accuracy of the CSSMO algorithm, we choose a cleaning process, minimum redundancy maximum relevance (mRMR) to lessen the gene expression of cancer datasets. Next, these subsets of genes are classified using deep learning (DL) to identify different groups or classes related to a particular cancer disease. Eight different benchmark microarray gene expression datasets of cancer have been utilized to analyze the performance of the proposed approach with different evaluation matrix such as recall, precision, F1-score, and confusion matrix. The proposed gene selection method with DL achieves much better classification accuracy than other existing DL and machine learning classification models with all large gene expression dataset of cancer., (© 2023. The Author(s).)
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- 2023
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12. Intraoperative intraarterial indocyanine green video-angiography for disconnection of a perimedullary arteriovenous fistula: illustrative case.
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Jung Y, Lindgren A, Ahmed SU, Radovanovic I, Krings T, and Andrade-Barazarte H
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Background: Intraarterial (IA) indocyanine green (ICG) angiography is an intraoperative imaging technique offering special and temporal characterization of vascular lesions with very fast dye clearance. The authors' aim is to demonstrate the use of IA ICG angiography to aid in the surgical treatment of a perimedullary thoracic arteriovenous fistula (AVF) in a hybrid operating room (OR)., Observations: A 31-year-old woman with a known history of spinal AVF presented with 6 weeks of lower-extremity weakness, gait imbalance, and bowel/bladder dysfunction. Magnetic resonance imaging revealed an extensive series of flow voids across the thoracic spine, most notably at T11-12. After partial embolization, she was taken for surgical disconnection in a hybrid OR. Intraoperative spinal digital subtraction angiography was performed to identify feeding vessels. When the target arteries were catheterized, 0.05 mg of ICG in 2 mL of saline was injected, and the ICG flow in each artery was recorded using the microscope. With an improved surgical understanding of the contributing feeding arteries, the authors achieved complete in situ disconnection of the AVF., Lessons: IA ICG angiography can be used in hybrid OR settings to illustrate the vascular anatomy of multifeeder perimedullary AVFs and confirm its postoperative disconnection with a fast dye clearance.
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- 2023
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13. Placing a Biventricular Implantable Cardioverter Defibrillator in Major Cardiac Dextroposition (Pseudo-Dextrocardia): A Case Report and Literature Review.
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Abdalla AS, Brands C, Aziz KT, Shimshak T, Windross D, and Ahmed SU
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We present an unusual case of a geriatric patient with right-sided cardiac displacement and rotation (Pseudo-Dextrocardia) secondary to radiation-induced pulmonary fibrosis (RIPF) after radiation for carcinoma of the right breast. This patient with heart failure with reduced ejection fraction (HFrEF) underwent cardiac resynchronization therapy with a defibrillator (CRT-D) for primary prevention of sudden cardiac death. Cannulization of the coronary sinus ostium was difficult, likely due to the significant cardiac displacement. However, after multiple attempts, it was eventually successful. The clinical manifestations, evaluation, and technical and procedural issues in this patient with an unusual anatomic variant are summarized., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abdalla et al.)
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- 2023
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14. Carotid Cavernous Sinus Fistula Supplied by an Embryological Variant of the Ophthalmic Artery Causing Posterior Ischemic Optic Neuropathy and Ophthalmoplegia.
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Handzic A, Ahmed SU, Mosimann P, Krings T, Daniel S, and Margolin E
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Competing Interests: The authors report no conflicts of interest.
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- 2023
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15. A magneto-activated nanoscale cytometry platform for molecular profiling of small extracellular vesicles.
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Chen K, Duong BTV, Ahmed SU, Dhavarasa P, Wang Z, Labib M, Flynn C, Xu J, Zhang YY, Wang H, Yang X, Das J, Zargartalebi H, Ma Y, and Kelley SO
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- Animals, Mice, CD8-Positive T-Lymphocytes, Cell Movement, Immunosuppression Therapy, B7-H1 Antigen genetics, Extracellular Vesicles
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Exosomal PD-L1 (exoPD-L1) has recently received significant attention as a biomarker predicting immunotherapeutic responses involving the PD1/PD-L1 pathway. However, current technologies for exosomal analysis rely primarily on bulk measurements that do not consider the heterogeneity found within exosomal subpopulations. Here, we present a nanoscale cytometry platform NanoEPIC, enabling phenotypic sorting and exoPD-L1 profiling from blood plasma. We highlight the efficacy of NanoEPIC in monitoring anti-PD-1 immunotherapy through the interrogation of exoPD-L1. NanoEPIC generates signature exoPD-L1 patterns in responders and non-responders. In mice treated with PD1-targeted immunotherapy, exoPD-L1 is correlated with tumor growth, PD-L1 burden in tumors, and the immune suppression of CD8+ tumor-infiltrating lymphocytes. Small extracellular vesicles (sEVs) with different PD-L1 expression levels display distinctive inhibitory effects on CD8 + T cells. NanoEPIC offers robust, high-throughput profiling of exosomal markers, enabling sEV subpopulation analysis. This platform holds the potential for enhanced cancer screening, personalized treatment, and therapeutic response monitoring., (© 2023. Springer Nature Limited.)
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- 2023
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16. Influence of geography, stroke timing, and weather conditions on transport and workflow times: Results from a longitudinal 5-year Canadian provincial registry.
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Kashani N, Ospel JM, Singh N, Zhou A, Ganesh A, Holodinsky JK, Almekhlafi M, Fouladirad S, Frost A, Yang L, Otani R, Newton B, Persad A, Wasyliw S, Graham BR, Hunter G, Gardner A, Cooley R, Ahmed SU, Peeling L, and Kelly ME
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Background: In areas with high population spread such as Saskatchewan, it can be challenging to provide timely endovascular stroke treatment (EVT) to patients living far away from comprehensive stroke centres (CSC). We assessed the association of geography, stroke timing and weather conditions on EVT workflow times and clinical outcomes in Saskatchewan., Methods: We included patients who underwent EVT between January 2017 and December 2022 in the province of Saskatchewan, Canada. Univariable and multivariable associations of time from last known well-to-CSC arrival, CSC arrival-to-reperfusion, and 90-day modified Rankin Score (mRS) with driving distance from patient home to CSC, transport mode, outdoor temperature and stroke timing (day & time) were assessed using descriptive statistics and multivariable regression., Results: Three-hundred-three patients in the province of Saskatchewan underwent EVT between January 2017 and December 2022. Distance from patient home to CSC (beta-coefficient per 10 km increase = 0.02, 95% CI: 0.01-0.03) and direct to CSC transport (beta-coefficient = -0.76, 95% CI = -1.01-[-0.51]) were associated with last known well to CSC arrival time. In-hospital stroke (beta-coefficient = 0.37, 95% CI: 0.16-0.58), direct-to-CSC transfer (beta-coefficient = 0.27, 95% CI: 0.13-0.41) and daytime stroke onset (beta-coefficient = -0.15, 95% CI: -0.28-[-0.04]) were associated with time from CSC arrival to reperfusion. No association with 90-day mRS was seen., Conclusion: Geographic factors and stroke timing were associated with EVT workflow times. However, no association with clinical outcomes was seen, suggesting that EVT patients living remote areas of Saskatchewan have similar benefit from EVT compared to urban areas. Every effort should be made to offer timely EVT to patients from remote areas.
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- 2023
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17. CO-WOA: Novel Optimization Approach for Deep Learning Classification of Fish Image.
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Aziz RM, Mahto R, Das A, Ahmed SU, Roy P, Mallik S, and Li A
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- Animals, Whales, Algorithms, Neural Networks, Computer, Image Processing, Computer-Assisted methods, Deep Learning
- Abstract
The most significant groupings of cold-blooded creatures are the fish family. It is crucial to recognize and categorize the most significant species of fish since various species of seafood diseases and decay exhibit different symptoms. Systems based on enhanced deep learning can replace the area's currently cumbersome and sluggish traditional approaches. Although it seems straightforward, classifying fish images is a complex procedure. In addition, the scientific study of population distribution and geographic patterns is important for advancing the field's present advancements. The goal of the proposed work is to identify the best performing strategy using cutting-edge computer vision, the Chaotic Oppositional Based Whale Optimization Algorithm (CO-WOA), and data mining techniques. Performance comparisons with leading models, such as Convolutional Neural Networks (CNN) and VGG-19, are made to confirm the applicability of the suggested method. The suggested feature extraction approach with Proposed Deep Learning Model was used in the research, yielding accuracy rates of 100 %. The performance was also compared to cutting-edge image processing models with an accuracy of 98.48 %, 98.58 %, 99.04 %, 98.44 %, 99.18 % and 99.63 % such as Convolutional Neural Networks, ResNet150V2, DenseNet, Visual Geometry Group-19, Inception V3, Xception. Using an empirical method leveraging artificial neural networks, the Proposed Deep Learning model was shown to be the best model., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)
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- 2023
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18. Spontaneous obliteration of a spinal perimedullary fistula.
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Nagendra S, Ahmed SU, and Krings T
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We herewith report a young patient who had an incidental spinal vascular malformation of the cervicomedullary junction discovered during a work-up for anosmia. Angiography demonstrated a perimedullary spinal arteriovenous fistula with supply from lateral spinal arteries arising from bilateral V3 level segmental arteries. It was decided to manage the patient conservatively with magnetic resonance imaging monitored biannually. On a recent follow-up magnetic resonance, nearly 10 years later, we noted a subtle change in caliber and imaging characteristics at the posterior margin of the cervical medullary junction. Repeat digital-subtraction angiography showed no evidence of early venous filling from the previously involved branches. Microcatheter exploration of the right lateral spinal artery confirmed spontaneous occlusion of the spinal perimedullary arteriovenous fistula, without any persistent shunting. Spontaneous resolution of a spinal vascular malformation is rare; this case demonstrates the dynamic nature of shunting vascular malformations and that spontaneous obliteration of arteriovenous shunts is possible.
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- 2023
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19. Immune responses in children after vaccination with a typhoid Vi-tetanus toxoid conjugate vaccine in Bangladesh.
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Khanam F, Babu G, Rahman N, Liu X, Rajib NH, Ahmed SU, Hossen MI, Biswas PK, Kelly S, Thesis-Nyland K, Mujadidi Y, McMillan NAJ, Pollard AJ, Clemens JD, and Qadri F
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- Humans, Child, Tetanus Toxoid, Salmonella typhi, Vaccines, Conjugate, Bangladesh, Immunoglobulin G, Antibodies, Bacterial, Vaccination, Antibody Formation, Typhoid Fever prevention & control, Typhoid-Paratyphoid Vaccines
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A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis (Vi-TT vs JE) to assess immune response. Blood was collected before vaccination, and on days 28, 545 and 730 post-vaccination and plasma anti-Vi-IgG response was measured. A robust, persistent antibody response was induced after single dose of Vi-TT, even after 2 years of vaccination. While there is no accepted serological antibody threshold of protection, analyzing the antibodies of children who received Vi-TT provides evidence that may later be useful in predicting population protection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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20. Stentrievers : An engineering review.
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Ahmed SU, Chen X, Peeling L, and Kelly ME
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- Humans, Treatment Outcome, Thrombectomy methods, Stents, Endovascular Procedures methods, Stroke surgery, Ischemic Stroke, Brain Ischemia surgery
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The advent of endovascular therapy for acute large vessel occlusion has revolutionized stroke treatment. Timely access to endovascular therapy, and the ability to restore intracranial flow in a safe, efficient, and efficacious manner has been critical to the success of the thrombectomy procedure. The stentriever has been a mainstay of endovascular stroke therapy, and current guidelines recommend the usage of stentrievers in the treatment of large vessel occlusion stroke. Despite the success of existing stentrievers, there continues to be significant development in the field, with newer stentrievers attempting to improve on each of the three key aspects of the thrombectomy procedure. Here, we elucidate the technical requirements that a stentriever must fulfill. We then review the basic variables of stent design, including the raw material and its form, fabrication method, geometric configuration, and further additions. Lastly, a selection of stentrievers from successive generations are reviewed using these engineering parameters, and clinical data is presented. Further avenues of stentriever development and testing are also presented.
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- 2023
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21. Measuring the Effectiveness of COVID-19 Vaccines Used during a Surge of the Delta Variant of SARS-CoV-2 in Bangladesh: A Test-Negative Design Evaluation.
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Khanam F, Islam MT, Ahmmed F, Ahmed SU, Hossen MI, Rajib MH, Haque S, Biswas PK, Tauheed I, Zaman K, Alam AN, Billah MM, Monalisa, Ashrafi SAA, Rahman MZ, Bin Manjur OH, Afrad MH, Shamsuzzaman SM, Saleh AA, Sumon MA, Rashed A, Bhuiyan MTR, Chowdhury F, Khan AI, Flora MS, Shirin T, Clemens JD, and Qadri F
- Abstract
Background: From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant., Methods: A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days' duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose., Results: In total, 313 cases were matched to 1196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: -21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines., Conclusions: Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries., Competing Interests: The authors declare no conflict of interest.
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- 2022
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22. Use of Antibacterial Envelopes for Prevention of Infection in Neuromodulation Implantable Pulse Generators.
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Persad AR, Ahmed SU, Mercure-Cyr R, Waterhouse K, and Vitali AM
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- Humans, Postoperative Complications, Reoperation, Retrospective Studies, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Prostheses and Implants
- Abstract
Background: Neuromodulation unit placement carries a historic infection rate as high as 12%. Treatment of such requires surgical removal and a long course of systemic antibiotics. Antibiotic-impregnated envelopes have been effective in preventing infection in implantable cardiac devices. At our center, 1 surgeon uses these envelopes with all implanted neuromodulation units., Objective: To assess the efficacy of antibacterial envelopes in prevention of infection in neuromodulation device placement., Methods: We conducted a retrospective cohort study of consecutive implantable pulse generator (IPG) unit implantation with an antibacterial envelope at a single center between October 2014 and December 2019. We collected demographic data, including postoperative infections, reoperations, and complications, associated with the IPGs. This cohort was then compared with a historical cohort of consecutive patients undergoing surgery before envelope usage (October 2007-April 2014)., Results: In the pre-envelope cohort of 151 IPGs placed in 116 patients, there were 18 culture-confirmed infections (11.9%). In the antibacterial envelope cohort of 233 IPGs placed in 185 patients, there were 5 culture-confirmed infections (2.1%). The absolute risk reduction of the antibacterial envelope was 9.85% (95% CI 4.3%-15.4%, P < .01). The number needed to treat was 10.1 (95% CI 6.5-23.1, P < .01) envelopes to prevent 1 IPG infection., Conclusion: We saw a reduced rate of infections in the antibacterial envelope cohort. Although this is likely multifactorial, our results suggest a benefit of antibacterial envelopes on infection after neuromodulation surgery., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)
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- 2022
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23. Endovascular retrieval of bullet fragment from the basilar artery terminus.
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Ahmed SU, Kelly ME, and Peeling L
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- Basilar Artery diagnostic imaging, Basilar Artery surgery, Child, Computed Tomography Angiography, Humans, Vertebral Artery diagnostic imaging, Vertebral Artery surgery, Embolization, Therapeutic, Endovascular Procedures methods
- Abstract
A pediatric patient presented after a gunshot injury to the right shoulder and thorax region, with injuries requiring a thoracotomy, tracheal repair, axillary artery repair, and external fixation of the humerus. A CT scan of the brain showed a metal fragment in the interpeduncular cistern. CT angiography confirmed a pellet occluding the basilar apex. Successful endovascular retrieval resulted in mobilizing the pellet from the basilar apex to the left vertebral artery proximal to the posterior inferior cerebellar artery. This vertebral artery was then sacrificed proximally to prevent re-embolization. We present our technique and discuss endovascular options for management of intracranial arterial embolization of bullet fragments., Competing Interests: Competing interests: SUA reports no competing interests. LP reports no competing interests. MK reports competing interests in the form of consulting fees from Imperative Care and research grant funding from the Saskatchewan Heath Research Foundation. In addition, he is a board member of the Heart and Stroke Foundation of Saskatchewan., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2022
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24. Phage-Based Profiling of Rare Single Cells Using Nanoparticle-Directed Capture.
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Ma Y, Chen K, Xia F, Atwal R, Wang H, Ahmed SU, Cardarelli L, Lui I, Duong B, Wang Z, Wells JA, Sidhu SS, and Kelley SO
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- Cell Line, Tumor, Cell Separation, Humans, Microfluidics, Tumor Microenvironment, Bacteriophages, Nanoparticles, Neoplastic Cells, Circulating
- Abstract
Advances in single-cell level profiling of the proteome require quantitative and versatile platforms, especially for rare cell analyses such as circulating tumor cell (CTC) profiling. Here we demonstrate an integrated microfluidic chip that uses magnetic nanoparticles to capture single tumor cells with high efficiency, permits on-chip incubation, and facilitates in situ cell-surface protein expression analysis. Combined with phage-based barcoding and next-generation sequencing technology, we were able to monitor changes in the expression of multiple surface markers stimulated in response to CTC adherence. Interestingly, we found fluctuations in the expression of Frizzled2 (FZD2) that reflected the microenvironment of the single cells. This platform has a high potential for in-depth screening of multiple surface antigens simultaneously in rare cells with single-cell resolution, which will provide further insights regarding biological heterogeneity and human disease.
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- 2021
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25. Prevalence of Gastroesophageal Reflux Disease and Associated Risk Factors in the Eastern Region, Saudi Arabia.
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Al Ghadeer HA, Alabbad ZE, AlShaikh SB, Ahmed SU, Bu-Khamseen AA, Alhashem AT, Alhamrani AH, AlGhadeer MR, Alibrahim DA, and Alkishi BM
- Abstract
Background Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder characterized by heartburn and acid regurgitation. A higher incidence is found in Arab countries. Untreated GERD has a negative impact on individuals that interfere with daily activities and impaired quality of life. This study aims to estimate the prevalence of GERD and associated risk factors in the Eastern region, Saudi Arabia. Material & Methodology A descriptive cross-sectional study was carried out among 1517 healthy participants from the Eastern province of Saudi Arabia from May to August 2021. The sample was randomly collected through a structured self-administered questionnaire. The questionnaire was composed of questions related to sociodemographic and lifestyle characteristics as risk factors for GERD. The existence of GERD was assessed by using GERD Questionnaire (GerdQ) for diagnosing GERD, when the score is 8 or more. Results A total of 1517 participants were included in the study: 58.8% male, 41.2% female; 9% of whom were pregnant. The age of participants ranged from 18 to 58 with a mean age of 27.5 ± 11.4 years old. The existence of GERD was 20.6% among the total participants, in which their GerdQ scores were 3-7 (68.9%), 8-10 (22.1%), and 8-11 (8.5%). The higher risk groups of having GERD were pregnant women, smoker, being male, regular usage of analgesia, soft drinks, and having a family history of GERD. Conclusion This study showed the prevalence of GERD among the general population of the Eastern region, Saudi Arabia was 20.6%. Several sociodemographic and lifestyle characteristics were associated with the disease. Further studies are needed to explore the role of psychological factors in developing GERD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Al Ghadeer et al.)
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- 2021
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26. Nerve root sedimentation sign on MRI: A triage screen for leg dominant symptoms?
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Huschi Z, Neuburger L, Ahmed SU, Cheng Y, and Fourney DR
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- Decompression, Surgical, Humans, Leg, Lumbar Vertebrae diagnostic imaging, Lumbar Vertebrae surgery, Magnetic Resonance Imaging, Male, Reproducibility of Results, Retrospective Studies, Spinal Stenosis diagnostic imaging, Spinal Stenosis surgery, Triage
- Abstract
Purpose: Surgical indications for lumbar spinal stenosis are controversial, but most agree that leg dominant pain is a better predictor of success after decompression surgery. The objective of this study is to analyze the ability of the Nerve Root Sedimentation Sign (SedSign) on MRI to differentiate leg dominant symptoms from non-specific low back pain., Methods: This was a retrospective review of 367 consecutive patients presenting with back and/or leg pain. Baseline clinical characteristics included Oswestry disability index (ODI), visual analog pain scores, EuroQol Group 5-Dimension Self-Report (EQ5D) and Saskatchewan Spine Pathway Classification (SSPc). Inter- and intra-rater reliability for SedSign was 73% and 91%, respectively (3 examiners)., Results: SedSign was positive in 111 (30.2%) and negative in 256 (69.8%) patients. On univariate analysis, a positive SedSign was correlated with age, male sex, several ODI components, EQ5D mobility, cross-sectional area (CSA) of stenosis, antero-posterior diameter of stenosis, and SSPc pattern 4 (intermittent leg dominant pain). On multivariate analysis, SedSign was associated with age, male sex, CSA stenosis and ODI walking distance. Patients with a positive SedSign were more likely to be offered surgery after referral (OR 2.65). The sensitivity and specificity for detecting all types of leg dominant pain were 37.4 and 82.8, respectively (ppv 77.5%, npv 43.8%)., Conclusions: Patients with a positive SedSign were more likely to be offered surgery, in particular non-instrumented decompression. The SedSign has high specificity for leg dominant pain, but the sensitivity is poor. As such, its use in triaging appropriate surgical referrals is limited., (© 2021. The Author(s).)
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- 2021
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27. Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.
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Qadri F, Khanam F, Liu X, Theiss-Nyland K, Biswas PK, Bhuiyan AI, Ahmmed F, Colin-Jones R, Smith N, Tonks S, Voysey M, Mujadidi YF, Mazur O, Rajib NH, Hossen MI, Ahmed SU, Khan A, Rahman N, Babu G, Greenland M, Kelly S, Ireen M, Islam K, O'Reilly P, Scherrer KS, Pitzer VE, Neuzil KM, Zaman K, Pollard AJ, and Clemens JD
- Subjects
- Adolescent, Bangladesh epidemiology, Child, Child, Preschool, Developing Countries, Encephalitis, Japanese epidemiology, Female, Humans, Infant, Japanese Encephalitis Vaccines administration & dosage, Male, Salmonella typhi immunology, Tetanus Toxoid immunology, Typhoid Fever epidemiology, Typhoid Fever immunology, Polysaccharides, Bacterial administration & dosage, Tetanus Toxoid therapeutic use, Typhoid Fever prevention & control, Typhoid-Paratyphoid Vaccines administration & dosage, Vaccination, Vaccines, Conjugate administration & dosage
- Abstract
Background: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings., Methods: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110., Findings: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed., Interpretation: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses., Funding: The study was funded by the Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests VEP has received reimbursement from Merck and Pfizer for travel expenses to scientific input engagements unrelated to the topic of this manuscript and is a member of the WHO Immunization and Vaccine-related Implementation Research Advisory Committee. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
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- 2021
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28. Multifunctional 3D-Printed Wound Dressings.
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Alizadehgiashi M, Nemr CR, Chekini M, Pinto Ramos D, Mittal N, Ahmed SU, Khuu N, Kelley SO, and Kumacheva E
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- Mice, Animals, Vascular Endothelial Growth Factor A, Silver, Bandages, Hydrogels, Anti-Bacterial Agents pharmacology, Printing, Three-Dimensional, Metal Nanoparticles therapeutic use
- Abstract
Personalized wound dressings provide enhanced healing for different wound types; however multicomponent wound dressings with discretely controllable delivery of different biologically active agents are yet to be developed. Here we report 3D-printed multicomponent biocomposite hydrogel wound dressings that have been selectively loaded with small molecules, metal nanoparticles, and proteins for independently controlled release at the wound site. Hydrogel wound dressings carrying antibacterial silver nanoparticles and vascular endothelial growth factor with predetermined release profiles were utilized to study the physiological response of the wound in a mouse model. Compared to controls, the application of dressings resulted in improvement in granulation tissue formation and differential levels of vascular density, dependent on the release profile of the growth factor. Our study demonstrates the versatility of the 3D-printed hydrogel dressings that can yield varied physiological responses in vivo and can further be adapted for personalized treatment of various wound types.
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- 2021
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29. Commentary: Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease.
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Ahmed SU, Lee H, and Steinberg GK
- Subjects
- Cohort Studies, Humans, North America epidemiology, Vascular Surgical Procedures, Cerebral Revascularization, Moyamoya Disease surgery
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- 2021
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30. A Novel Curriculum on Using Life Expectancy to Inform Cancer Screening in Older Adults.
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Ahmed SU, Burke M, McGuire M, Massare J, Boyd CM, Pollack CE, Lentz C, and Schoenborn NL
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- Aged, Female, Humans, Internet-Based Intervention, Male, Medical Overuse prevention & control, Physician-Patient Relations, Program Evaluation, Staff Development methods, Unnecessary Procedures, Early Detection of Cancer methods, Early Detection of Cancer standards, Education, Distance methods, Life Expectancy, Physicians, Primary Care education, Physicians, Primary Care psychology, Self Concept
- Abstract
Background: Many older adults with limited life expectancy still receive cancer screening. One potential contributor is that primary care providers (PCP) are not trained to incorporate life expectancy in cancer screening recommendations. We describe the development and evaluation of a novel curriculum to address this need., Methods: We developed and implemented a web-based learning module within a large Maryland group practice with PCPs for older adults. We assessed attitude, knowledge, self-efficacy, and self-reported behavior outcomes before the module, immediately after completing the module, and 6 months afterwards., Results: Of 172 PCPs who were invited, 86 (50%) completed the module and of these, 50 (58.1%) completed the 6-months follow up survey. Immediately after the module, there was a significant increase in perceived importance of life expectancy (increase of 0.50 point on 10-point scale, 95% confidence intervals (CI) = 0.27-0.73), confidence in predicting life expectancy (increase of 2.32 points on 10-point scale, 95% CI = 1.95-2.70) and confidence in discussion screening cessation (increase of 1.69 points on 10-point scale, 95% CI = 1.37-2.02). Knowledge in patient-preferred communication strategies improved from 55% correct response to 97% (P < .001). However, most of these improvements dissipated by 6 months and there was no change in self-reported behavior at 6 months compared to baseline (P = .34)., Conclusion: Although the module resulted in significant short-term improvement in attitude, knowledge, and self-efficacy, the changes were not sustained over time. Educational interventions such as this can be coupled with ongoing reinforcing strategies and/or decision support interventions to improve cancer-screening practices in older adults., (© 2021 The American Geriatrics Society.)
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- 2021
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31. Tracking the expression of therapeutic protein targets in rare cells by antibody-mediated nanoparticle labelling and magnetic sorting.
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Labib M, Wang Z, Ahmed SU, Mohamadi RM, Duong B, Green B, Sargent EH, and Kelley SO
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- Animals, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal pharmacokinetics, Biomarkers, Tumor analysis, Biomarkers, Tumor chemistry, Female, Humans, Male, Mice, Mice, Nude, Neoplastic Cells, Circulating chemistry, Prostatic Neoplasms chemistry, Prostatic Neoplasms metabolism, Proteins analysis, Proteins chemistry, Proteins metabolism, Antibodies, Monoclonal metabolism, Biomarkers, Tumor metabolism, Cytological Techniques methods, Magnetite Nanoparticles chemistry, Neoplastic Cells, Circulating metabolism
- Abstract
Molecular-level features of tumours can be tracked using single-cell analyses of circulating tumour cells (CTCs). However, single-cell measurements of protein expression for rare CTCs are hampered by the presence of a large number of non-target cells. Here, we show that antibody-mediated labelling of intracellular proteins in the nucleus, mitochondria and cytoplasm of human cells with magnetic nanoparticles enables analysis of target proteins at the single-cell level by sorting the cells according to their nanoparticle content in a microfluidic device with cell-capture zones sandwiched between arrays of magnets. We used the magnetic labelling and cell-sorting approach to track the expression of therapeutic protein targets in CTCs isolated from blood samples of mice with orthotopic prostate xenografts and from patients with metastatic castration-resistant prostate cancer. We also show that mutated proteins that are drug targets or markers of therapeutic response can be directly identified in CTCs, analysed at the single-cell level and used to predict how mice with drug-susceptible and drug-resistant pancreatic tumour xenografts respond to therapy.
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- 2021
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32. FOLFOXIRI Versus Doublet Regimens in Right-Sided Metastatic Colorectal Cancer: Focus on Subsequent Therapies and Impact on Overall Survival.
- Author
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Jácome AA, Kee B, Fogelman D, Dasari A, Shureiqi I, Raghav K, Morris V, Johnson B, Overman M, Wolff R, Kopetz S, Rogers J, Ahmed SU, Mehdizadeh A, Rothschild N, and Eng C
- Subjects
- Adult, Aged, Aged, 80 and over, Camptothecin administration & dosage, Clinical Decision-Making, Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Drug Administration Schedule, Female, Fluorouracil administration & dosage, Follow-Up Studies, Humans, Leucovorin administration & dosage, Male, Middle Aged, Organoplatinum Compounds administration & dosage, Patient Selection, Prognosis, Progression-Free Survival, Retrospective Studies, Survival Rate, Young Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bevacizumab administration & dosage, Camptothecin analogs & derivatives, Colorectal Neoplasms therapy, Metastasectomy statistics & numerical data
- Abstract
Introduction: It has been determined that right-sided metastatic colorectal cancer (mCRC) has a worse prognosis for overall survival (OS). Currently, there is no consensus on the best systemic regimen for treatment-naive right-sided tumors. We compared the impact of subsequent therapies on OS of patients treated with FOLFOXIRI (leucovorin, 5-fluorouracil, oxaliplatin, irinotecan) versus doublet regimens., Patients and Methods: Data of patients with treatment-naive right-sided mCRC who received FOLFOXIRI or doublet regimens between January 2001 to December 2018 were retrospectively analyzed. OS was compared between the two groups, and prognostic factors were assessed by multivariate analysis., Results: A total of 196 patients were selected; 33 patients received FOLFOXIRI and 163 patients doublet therapy. Median follow-up was 82.3 months. The FOLFOXIRI cohort received fewer subsequent lines of therapies (61% vs. 78%, P = .043). The greater the number of subsequent lines of therapy, the lower the risk of death (hazard ratio [95% confidence interval] 0.67 [0.46-0.99], 0.62 [0.45-0.86], and 0.56 [0.39-0.81] for > 1, > 2, and > 3 lines, respectively). By multivariate analysis, metastasectomy and bevacizumab with subsequent lines of therapy were the variables with greatest positive impact on OS (respectively, hazard ratio [95% confidence interval] 0.54 [0.38-0.78] and 0.61 [0.44-0.84])., Conclusion: Patients with treatment-naive right-sided mCRC who received front-line FOLFOXIRI had a lower number of subsequent therapies than patients who received doublet regimens. Our findings highlight the relevance of the continuum of care in mCRC, regardless of the first-line regimen, and the importance of careful selection of patients for the FOLFOXIRI regimen., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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33. Baseline assessment of water quality and ecological indicators in Penaeus vannamei farm wastewater along the Southeast coast of India.
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Dinesh Kumar S, Santhanam P, Krishnaveni N, Raju P, Begum A, Ahmed SU, Perumal P, Pragnya M, Dhanalakshmi B, and Kim MK
- Subjects
- Animals, India, Ponds, Wastewater, Water Quality, Penaeidae
- Abstract
The present study aimed to investigate the water quality characteristics and the ecological indicators of wastewater of white legged shrimp Penaeus vannamei ponds along the Southeast coast of India. The wastewater samples were collected from 15 shrimp farms covering 11 districts located along the coastal line of Tamil Nadu and Puducherry, India. By adopting standard methods, the collected samples were subjected to analyses of physico-chemical and biological characteristics, especially the microbial load and metal and plankton composition. The nitrate-nitrogen, ammonia-nitrogen, THB, TCB, and Cu concentrations of the samples were found to exceed the permissible limit as recommended by WHO, USEPA, CPCB, and CAA. Principal component analysis and canonical correspondence analysis have suggested that the phosphate, nitrate, silicate, ammonia, and total phosphorus are the important chemical factors. The generated data would be of interest to farmers for their shrimp crop management vis-à-vis culture pond wastewater treatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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34. Outcomes with anti-EGFR monoclonal antibodies in metastatic and recurrent anal squamous cell carcinoma.
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Rogers JE, Jácome AAA, Ohinata A, Wolff R, Morris VK, Johnson B, Mehdizadeh A, Rothschild ND, Ahmed SU, Guerra JL, and Eng C
- Subjects
- Adult, Aged, Antibodies, Monoclonal pharmacology, Antineoplastic Agents administration & dosage, Antineoplastic Agents pharmacology, Anus Neoplasms genetics, Anus Neoplasms pathology, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Class I Phosphatidylinositol 3-Kinases genetics, Female, Follow-Up Studies, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Progression-Free Survival, Retrospective Studies, Survival Rate, Antibodies, Monoclonal administration & dosage, Anus Neoplasms drug therapy, Carcinoma, Squamous Cell drug therapy, ErbB Receptors antagonists & inhibitors
- Abstract
Objectives: Metastatic squamous cell carcinoma anal cancer (SCCA) is rare. Prospective data recommends front-line platinum doublet combinations and second-line anti-programmed death-1 therapy. Standard therapy beyond these treatments are currently unknown. We evaluated anti-EGFR monoclonal antibody (mAb) outcomes in metastatic SCCA., Methods: Metastatic SCCA patients given anti-EGFR mAb from Oct 2011-May 2018 were included. Primary endpoints included best response, progression-free survival, and overall survival., Results: 56 patients were evaluated with a median of one prior therapy. Most patients (~90%) received anti-EGFR mAbs with chemotherapy. Response rate (any response) was 41%. Median PFS was 4.3 months with a median OS of 16 M. Seven patients with disease control proceeded onto maintenance therapy (anti-EGFR mAb ± a fluoropyrimidine) with a median PFS of 13.8 M. Next generation sequencing of 16 pts (28%) showed 4 pts had a PIK3CA mutation with 3 of these 4 patients demonstrating progression on initial restaging., Conclusion: Our analysis suggests anti-EGFR mAb therapy with chemotherapy provides clinical benefit in previously treated metastatic SCCA. Our maintenance therapy and the role of PIK3CA MT outcomes were thought-provoking., Expert Opinion: Metastatic SCCA patients have limited options; therefore, anti-EGFR mAbs may provide benefit in the treatment armamentarium and should be further explored.
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- 2020
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35. Fluorescent Droplet Cytometry for On-Cell Phenotype Tracking.
- Author
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Yang X, Liu W, Chan DC, Ahmed SU, Wang H, Wang Z, Nemr CR, and Kelley SO
- Subjects
- Cell Line, Tumor, Humans, Male, Optical Imaging, Particle Size, Phenotype, Surface Properties, Flow Cytometry, Fluorescent Dyes chemistry, Microfluidic Analytical Techniques, Neoplasms pathology, Single-Cell Analysis
- Abstract
Profiling the heterogeneous phenotypes of live cancer cells is a key capability that requires single-cell analysis. However, acquiring information at the single-cell level for live cancer cells is challenging when small collections of cells are being targeted. Here, we report single-cell analysis for low abundance cells enabled by fluorescent droplet cytometry (FDC), an approach that uses a biomarker-specific enzymatic fluorescent assay carried out using a droplet microfluidic platform. FDC utilizes DNA-functionalized antibodies in droplets to achieve specific on-cell target detection and enables characterization and profiling of live cancer cells with single-cell resolution based on their surface phenotype. Using this approach, we achieve live-cell phenotypic profiling of multiple surface markers acquired with small (<40 cells) collections of cells.
- Published
- 2020
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36. Hand Sewn versus Stapled Closure of Duodenal Stump after Gastric Resection.
- Author
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Biswas AK, Mahmud F, Siddique AB, Ahmed SU, Taher MA, and Kibria CS
- Subjects
- Anastomosis, Surgical, Bangladesh, Female, Humans, Male, Postoperative Complications, Prospective Studies, Retrospective Studies, Surgical Stapling, Suture Techniques, Duodenum, Gastrectomy
- Abstract
This prospective comparative study was done to compare the outcome of stapled closure of the duodenal stump with hand-sewn closure during gastric resection in terms of total operating time, postoperative duodenal stump leakage, postoperative hospital stay, and surgical cost. This study was conducted from January 2013 to August 2014. Patients who were admitted to the Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh with the indication of distal or total gastrectomy were included in the study. A total of 32 patients were enrolled in this study with 16 in each group, they were divided either into Group I (Hand Sewn) or Group II (stapling). Mean±SD age of Group I was 53.38±8.69 and Group II was 50.88±9.56 (p=0.445). Male patients were predominant than the female with a male: female ratio being 3.57:1. Mean±SD total operating time was 154.38±16.32 minutes and 136.88±17.40 minutes in Group I and Group II respectively (p=0.001). In Group I, 2(12.5%) patients and in Group II, 1(6.3%) patient had duodenal stump leakage which showed no statistically significant difference (p=0.999). Postoperative hospital stay had no statistically significant difference (p=0.923). The surgical cost had a significant difference (p=0.001) which is more in Group II. This study showed there was a significant reduction in total operating time but there was no significant difference in occurring of duodenal stump leakage or postoperative hospital stay. However, use of stapler hastens the surgeon's job and it relieves extra pressure of them.
- Published
- 2020
37. Traumatic spinal cord injuries among Aboriginal and non-Aboriginal populations of Saskatchewan: a prospective outcomes study.
- Author
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Ahmed SU, Humphreys S, Rivers C, Jeffrey M, and Fourney DR
- Subjects
- Adult, Female, Humans, Incidence, Male, Middle Aged, Patient Discharge trends, Retrospective Studies, Saskatchewan epidemiology, Ethnicity, Hospitals, University statistics & numerical data, Outcome Assessment, Health Care methods, Registries, Risk Assessment methods, Spinal Cord Injuries ethnology
- Abstract
Background: People of Aboriginal (Indigenous) ancestry are more likely to experience traumatic spinal cord injury (TSCI) than other Canadians; however, outcome studies are limited. This study aims to compare Aboriginal and non-Aboriginal populations with acute TSCI with respect to preinjury baseline characteristics, injury severity, treatment, outcomes and length of stay., Methods: This was a retrospective analysis of participants with a TSCI who were enrolled in the prospective Rick Hansen Spinal Cord Injury Registry (RHSCIR), Saskatoon site (Royal University Hospital), between Feb. 13, 2010, and Dec. 17, 2016. Demographic, injury and management data were assessed to identify any differences between the populations., Results: Of the 159 patients admitted to Royal University Hospital with an acute TSCI during the study period, 62 provided consent and were included in the study. Of these, 21 self-identified as Aboriginal (33.9%) and 41 as non-Aboriginal (66.1%) on treatment intake forms. Compared with non-Aboriginal participants, Aboriginal participants were younger, had fewer medical comorbidities, had a similar severity of neurologic injury and had similar clinical outcomes. However, the time to discharge to the community was significantly longer for Aboriginal participants (median 104.0 v. 34.0 d, p = 0.016). Although 35% of non-Aboriginal participants were discharged home from the acute care site, no Aboriginal participants were transferred home directly., Conclusion: This study suggests a need for better allocation of resources for transition to the community for Aboriginal people with a TSCI in Saskatchewan. We plan to assess outcomes from TSCI for Aboriginal people across Canada., Competing Interests: None declared., (© 2020 Joule Inc. or its licensors.)
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- 2020
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38. Nanostructured Architectures Promote the Mesenchymal-Epithelial Transition for Invasive Cells.
- Author
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Wang Z, Xia F, Labib M, Ahmadi M, Chen H, Das J, Ahmed SU, Angers S, Sargent EH, and Kelley SO
- Subjects
- Cell Differentiation, Cell Line, Tumor, Cell Movement, Epithelial-Mesenchymal Transition, Humans, Male, Glycogen Synthase Kinase 3, Nanostructures
- Abstract
Dynamic modulation of cellular phenotypes between the epithelial and mesenchymal states-the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET)-plays an important role in cancer progression. Nanoscale topography of culture substrates is known to affect the migration and EMT of cancer cells. However, existing platforms heavily rely on simple geometries such as grooved lines or cylindrical post arrays, which may oversimplify the complex interaction between cells and nanotopography in vivo . Here, we use electrodeposition to construct finely controlled surfaces with biomimetic fractal nanostructures as a means of examining the roles of nanotopography during the EMT/MET process. We found that nanostructures in the size range of 100 to 500 nm significantly promote MET for invasive breast and prostate cancer cells. The "METed" cells acquired distinct expression of epithelial and mesenchymal markers, displayed perturbed morphologies, and exhibited diminished migration and invasion, even after the removal of a nanotopographical stimulus. The phosphorylation of GSK-3 was decreased, which further tuned the expression of Snail and modulated the EMT/MET process. Our findings suggest that invasive cancer cells respond to the geometries and dimensions of complex nanostructured architectures.
- Published
- 2020
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39. Atypical language localization in right temporal lobe epilepsy: An fMRI case report.
- Author
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Gould L, Wu A, Tellez-Zenteno JF, Neudorf J, Kress S, Gibb K, Ekstrand C, Dabirzadeh H, Ahmed SU, and Borowsky R
- Abstract
We report a 41- year-old, left-handed patient with drug-resistant right temporal lobe epilepsy (TLE). Presurgical fMRI was conducted to examine whether the patient had language functioning in the right hemisphere given that left-handedness is associated with a higher prevalence of right hemisphere dominance for language. The fMRI results revealed bilateral activation in Broca's and Wernicke's areas and activation of eloquent cortex near the region of planned resection in the right temporal lobe. Due to right temporal language-related activation, the patient underwent an awake right-sided temporal lobectomy with intraoperative language mapping. Intraoperative direct cortical stimulation (DCS) was conducted in the regions corresponding to the fMRI activation, and the patient showed language abnormalities, such as paraphasic errors, and speech arrest. The decision was made to abort the planned anterior temporal lobe procedure, and the patient instead underwent a selective amygdalohippocampectomy via the Sylvian fissure at a later date. Post-operatively the patient was seizure-free with no neurological deficits. Taken together, the results support previous findings of right hemisphere language activation in left-handed individuals, and should be considered in cases in which presurgical localization is conducted for left-hand dominant patients undergoing neurosurgical procedures., (© 2020 The Authors.)
- Published
- 2020
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40. Ultrasensitive and rapid quantification of rare tumorigenic stem cells in hPSC-derived cardiomyocyte populations.
- Author
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Wang Z, Gagliardi M, Mohamadi RM, Ahmed SU, Labib M, Zhang L, Popescu S, Zhou Y, Sargent EH, Keller GM, and Kelley SO
- Subjects
- Cell Differentiation, Cell- and Tissue-Based Therapy, Humans, Myocytes, Cardiac, Pluripotent Stem Cells
- Abstract
The ability to detect rare human pluripotent stem cells (hPSCs) in differentiated populations is critical for safeguarding the clinical translation of cell therapy, as these undifferentiated cells have the capacity to form teratomas in vivo. The detection of hPSCs must be performed using an approach compatible with traceable manufacturing of therapeutic cell products. Here, we report a novel microfluidic approach, stem cell quantitative cytometry (SCQC), for the quantification of rare hPSCs in hPSC-derived cardiomyocyte (CM) populations. This approach enables the ultrasensitive capture, profiling, and enumeration of trace levels of hPSCs labeled with magnetic nanoparticles in a low-cost, manufacturable microfluidic chip. We deploy SCQC to assess the tumorigenic risk of hPSC-derived CM populations in vivo. In addition, we isolate rare hPSCs from the differentiated populations using SCQC and characterize their pluripotency., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
- Published
- 2020
- Full Text
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41. MRA versus DSA for the follow-up imaging of intracranial aneurysms treated using endovascular techniques: a meta-analysis.
- Author
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Ahmed SU, Mocco J, Zhang X, Kelly M, Doshi A, Nael K, and De Leacy R
- Subjects
- Adult, Aged, Angiography, Digital Subtraction standards, Female, Follow-Up Studies, Humans, Magnetic Resonance Angiography standards, Middle Aged, Treatment Outcome, Angiography, Digital Subtraction methods, Endovascular Procedures methods, Intracranial Aneurysm diagnostic imaging, Intracranial Aneurysm surgery, Magnetic Resonance Angiography methods
- Abstract
Background: Treated aneurysms must be followed over time to ensure durable occlusion, as more than 20% of endovascularly treated aneurysms recur. While digital subtraction angiography (DSA) remains the gold standard, magnetic resonance angiography (MRA) is attractive as a non-invasive follow-up technique. Two different MRA techniques have traditionally been used: time-of-flight (TOF) and contrast-enhanced (CE) MRA. We analysed data from studies comparing MRA techniques with DSA for the follow-up of aneurysms undergoing endovascular treatment. Subgroup analysis of stent-assisted coiling (SAC) and flow diversion (FD) techniques was completed., Methods: Comprehensive searches using the Embase, PubMed, and Cochrane databases were performed and updated to November 2018. Pooled sensitivity and specificity were calculated using aneurysm occlusion status as defined by the Raymond-Roy occlusion grading scale., Results: The literature search yielded 1579 unique titles. Forty-three studies were included. For TOF-MRA, sensitivity and specificity of all aneurysms undergoing endovascular therapy were 88% and 94%, respectively. For CE-MRA, the sensitivity and specificity were 88% and 96%, respectively. For SAC and FD techniques, sensitivity and specificity of TOF-MRA were 86% and 95%, respectively. CE-MRA had sensitivity and specificity of 90% and 92%., Conclusion: MRA is a reliable modality for the follow-up of aneurysms treated using endovascular techniques. While the data are limited, MRA techniques can also be used to reliably follow patients undergoing FD and SAC. However, clinical factors must be used to optimize follow-up regimens for individual patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
- Full Text
- View/download PDF
42. Electrosurgery Dissection versus Sharp Dissection: Effect on Early Postoperative Wound Complications in Modified Radical Mastectomy.
- Author
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Masud Rana AM, Ahmed SU, Alam F, Joardar AI, Chowdhury AK, Bari MA, Saifullah M, Haque MS, and Haque MM
- Subjects
- Bangladesh, Electrosurgery, Female, Humans, Postoperative Complications, Breast Neoplasms surgery, Diathermy, Mastectomy methods, Surgical Wound Infection
- Abstract
Modified radical mastectomy (MRM) is still the most commonly performed operation for breast cancer, despite the trends toward breast-conserving treatment. Since 1970s, electrosurgery (also known as electrocautery, diathermy) has been a widespread surgical tool to raise flaps and excise the breast specimen in order to perform a bloodless mastectomy. Use of diathermy has been well blamed for wound complications. To prevent undue delay in the adjuvant treatment, it is important to minimize the surgical complications. This quasi experimental study was conducted in the Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh to evaluate the effects of electrosurgery and sharp dissection on early postoperative wound complications in MRM. 46 patients were included in the study (23 in each group). Data analysis done in SPSS version 23.0 and 'p' value <0.05 considered significant at 95% confidence interval. In Electrosurgery Dissection (ED) group mean duration of drainage was 7.8±1.2 days and in Sharp Dissection (SD) group 6.4±1.0 days (p value 0.000). Mean total drainage in ED group found 1082±287ml and in SD group 693±194ml (p value 0.000). Seroma formation found 7(30.4%) in ED group and 3(13.0%) in SD group (p value 0.004). Wound dehiscence found 5(21.7%) in ED group and 2(8.7%) in SD group (p value 0.013). Flap necrosis rate was 4(17.4%) and 1(4.4%) in ED and SD group respectively (p=0.003). Demographic and clinical variables were similar or differences were not statistically significant in two groups. No difference found in operating time and wound infection rate in two groups. The result of the study showed that, electrocautery dissection caused early postoperative wound complications more than the sharp dissection.
- Published
- 2019
43. Role of Endoscopic Ultrasound Guided Fine Needle Aspiration in the Diagnosis of Pancreatic Lesions.
- Author
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Alam AT, Chowdhury AK, Das CR, Ahmed SU, and Yousuf NA
- Subjects
- Bangladesh, Female, Humans, Male, Pancreatic Diseases pathology, Pancreatic Neoplasms pathology, Endoscopic Ultrasound-Guided Fine Needle Aspiration methods, Pancreas diagnostic imaging, Pancreatic Diseases diagnosis, Pancreatic Neoplasms diagnosis
- Abstract
To evaluate the diagnostic utility of endoscopic ultrasound guided fine needle aspiration (EUS-FNA) of pancreatic lesions, EUS-FNA was carried out on a total of 28 cases at the Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from June 2015 to August 2016. Clinical impression was compared with the final cytological diagnosis and the percentage of non diagnostic smears was calculated. The lesions were categorized according to cytological report. Out of 28 cases, 3(10.71%) cases were normal, 6 cases (21.43%) were reported as inconclusive while a definite diagnosis was given in 19 cases (67.85%). The mean patient age was 47.82 years. There were 16(57.1%) males and 12(42.9%) females. The most common site biopsied was pancreatic head in 21cases (75%) followed by tail in 5 cases (17.9%) & body in 2(7.1%) cases. The average number of passes made was two. Endoscopic Ultrasound Guided Fine-Needle Aspiration in the diagnosis of pancreatic lesion is a useful procedure.
- Published
- 2019
44. Permanent implantation of the Solitaire device as a bailout technique for large vessel intracranial occlusions.
- Author
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Ahmed SU, Mann J, Houde J, Barber E, Kelly ME, and Peeling L
- Subjects
- Aged, Aged, 80 and over, Brain Ischemia diagnostic imaging, Brain Ischemia surgery, Female, Humans, Male, Middle Aged, Stroke diagnostic imaging, Stroke surgery, Thrombectomy instrumentation, Thrombectomy methods, Treatment Outcome, Blood Vessel Prosthesis, Cerebrovascular Disorders diagnostic imaging, Cerebrovascular Disorders surgery, Self Expandable Metallic Stents
- Abstract
The Solitaire (Medtronic Inc, Mansfield, Massachusetts, USA) is a stentriever device for endovascular treatment of acute ischemic stroke. Temporary endovascular bypass and mechanical thrombectomy are well-described applications of this device. However, few reports of permanent stent placement have been published. We present a series of five cases in which the Solitaire stent was implanted to restore distal flow after failure of conventional mechanical thrombectomy. All patients presented with large vessel occlusions with thrombi that were resistant to retrieval or suction-aspiration. Immediately after implantation the patients were given a loading dose of abciximab and then transitioned to dual antiplatelet therapy within 24 hours. Our series suggests that permanent deployment of the Solitaire may be considered as a bailout technique in the treatment of cerebral large vessel occlusion. Long-term antiplatelet therapy is required after deployment., Competing Interests: Competing interests: MEK: consultant, Medtronic; LP: consultant, Medtronic., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
- Full Text
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45. Prismatic Deflection of Live Tumor Cells and Cell Clusters.
- Author
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Aldridge PM, Mukhopadhyay M, Ahmed SU, Zhou W, Christinck E, Makonnen R, Sargent EH, and Kelley SO
- Subjects
- Cell Line, Tumor, Humans, Male, Nanoparticles chemistry, Prostatic Neoplasms blood, Cell Separation, Microfluidic Analytical Techniques, Neoplastic Cells, Circulating pathology, Prostatic Neoplasms pathology
- Abstract
The analysis of heterogeneous subpopulations of circulating tumor cells (CTCs) is critical to enhance our understanding of cancer metastasis and enable noninvasive cancer diagnosis and monitoring. The phenotypic variability and plasticity of these cells-properties closely linked to their clinical behavior-demand techniques that isolate viable, discrete fractions of tumor cells for functional assays of their behavior and detailed analysis of biochemical properties. Here, we introduce the Prism Chip, a high-resolution immunomagnetic profiling and separation chip which harnesses a cobalt-based alloy to separate a flowing stream of nanoparticle-bound tumor cells with differential magnetic loading into 10 discrete streams. Using this approach, we achieve exceptional purity (5.7 log white blood cell depletion) of isolated cells. We test the differential profiling function of the integrated device using prostate cancer blood samples from a mouse xenograft model. Using integrated graphene Hall sensors, we demonstrate concurrent automated profiling of single cells and CTC clusters that belong to distinct subpopulations based on protein surface expression.
- Published
- 2018
- Full Text
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46. Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-like Cells.
- Author
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Carruthers RD, Ahmed SU, Ramachandran S, Strathdee K, Kurian KM, Hedley A, Gomez-Roman N, Kalna G, Neilson M, Gilmour L, Stevenson KH, Hammond EM, and Chalmers AJ
- Subjects
- AC133 Antigen genetics, Ataxia Telangiectasia Mutated Proteins antagonists & inhibitors, Ataxia Telangiectasia Mutated Proteins genetics, Cell Line, Tumor, DNA Breaks, Double-Stranded drug effects, DNA Breaks, Double-Stranded radiation effects, DNA Damage drug effects, DNA Damage radiation effects, DNA Replication drug effects, DNA Replication radiation effects, Glioblastoma drug therapy, Glioblastoma pathology, Glioblastoma radiotherapy, Humans, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local radiotherapy, Phthalazines pharmacology, Piperazines pharmacology, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Carcinogenesis, Glioblastoma genetics, Neoplasm Recurrence, Local genetics, Neoplastic Stem Cells, Radiation Tolerance genetics
- Abstract
Glioblastoma (GBM) is a lethal primary brain tumor characterized by treatment resistance and inevitable tumor recurrence, both of which are driven by a subpopulation of GBM cancer stem-like cells (GSC) with tumorigenic and self-renewal properties. Despite having broad implications for understanding GSC phenotype, the determinants of upregulated DNA-damage response (DDR) and subsequent radiation resistance in GSC are unknown and represent a significant barrier to developing effective GBM treatments. In this study, we show that constitutive DDR activation and radiation resistance are driven by high levels of DNA replication stress (RS). CD133
+ GSC exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133- non-GSC in vitro ; immunofluorescence studies confirmed these observations in a panel of orthotopic xenografts and human GBM specimens. Exposure of non-GSC to low-level exogenous RS generated radiation resistance in vitro , confirming RS as a novel determinant of radiation resistance in tumor cells. GSC exhibited DNA double-strand breaks, which colocalized with "replication factories" and RNA: DNA hybrids. GSC also demonstrated increased expression of long neural genes (>1 Mbp) containing common fragile sites, supporting the hypothesis that replication/transcription collisions are the likely cause of RS in GSC. Targeting RS by combined inhibition of ATR and PARP (CAiPi) provided GSC-specific cytotoxicity and complete abrogation of GSC radiation resistance in vitro These data identify RS as a cancer stem cell-specific target with significant clinical potential. Significance: These findings shed new light on cancer stem cell biology and reveal novel therapeutics with the potential to improve clinical outcomes by overcoming inherent radioresistance in GBM. Cancer Res; 78(17); 5060-71. ©2018 AACR ., (©2018 American Association for Cancer Research.)- Published
- 2018
- Full Text
- View/download PDF
47. Intra- and inter-nanocrystal charge transport in nanocrystal films.
- Author
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Aigner W, Bienek O, Falcão BP, Ahmed SU, Wiggers H, Stutzmann M, and Pereira RN
- Abstract
The exploitation of semiconductor nanocrystal (NC) films in novel electronic and optoelectronic applications requires a better understanding of charge transport in these systems. Here, we develop a model of charge transport in NC films, based on a generalization of the concept of transport energy level ET to nanocrystal assemblies, which considers both intra- and inter-NC charge transfer processes. We conclude that the role played by each of these processes can be probed from temperature-dependent measurements of charge carrier density n and mobility μ in the same films. The model also enables the determination of the position of the Fermi energy level EF with respect to ET, an important parameter of charge transport in semiconductor materials, from the temperature dependence of n. Moreover, we provide support to an essentially temperature-independent intra-NC charge carrier mobility, considered in the transport level concept, and consequently the frequently observed temperature dependence of the overall mobility μ in NC films results from a temperature variation of the inter-NC charge transport processes. Importantly, we also conclude that the temperature dependence of conductivity in NC films should result in general from a combination of temperature variations of both n and μ. By applying the model to solution-processed Si NC films, we conclude that transport within each NC is similar to that in amorphous Si (a-Si), with charges hopping along band tail states located below the conduction band edge. For Si NCs, we obtain values of ET - EF of ∼0.25 eV. The overall mobility μ in Si NC films is significantly further reduced with respect to that typically found in a-Si due to the additional transport constraints imposed by inter-NC transfer processes inherent to a nanoparticulate film. Our model accounting for inter- and intra-NC charge transport processes provides a simple and more general description of charge transport that can be broadly applied to films of semiconductor NCs.
- Published
- 2018
- Full Text
- View/download PDF
48. Role of thrombophilia in splanchnic venous thrombosis in acute pancreatitis.
- Author
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Ahmed SU, Rana SS, Ahluwalia J, Varma N, Sharma R, Gupta R, and Kang M
- Abstract
Background: Splanchnic venous thrombosis (SVT) is a common vascular complication of acute pancreatitis (AP). We conducted this study to prospectively investigate the frequency, risk factors, and extent of SVT in patients with AP and to evaluate the role of thrombophilia in its causation., Methods: Patients with AP presenting between January 2015 and June 2016 were prospectively evaluated with contrast-enhanced computed tomography (CT) for the presence of SVT. These patients underwent a detailed analysis of coagulation parameters., Results: We evaluated 96 patients with AP (73 male, mean age 31.85±13.34 years), of whom 26 (27.1%) had SVT. Splenic vein, portal vein, and superior mesenteric vein involvement were seen in 22 (84.6%), 11 (42.3%), and 4 (15.3%) patients, respectively. Necrotizing pancreatitis, CT severity index (CTSI) >6 and modified CTSI >6 were significantly more frequent in patients with SVT than in those without (96.2% vs. 78.6%, 76.9% vs. 47.1%, and 92.3% vs. 67.1%, respectively). Proteins C and S, and antithrombin III deficiency were found in 23.8%, 33.3% and 31.0% of patients, respectively. Anti-β2-glycoprotein I and lupus anticoagulant were positive in 4.8% and 11.9% of patients, respectively. Factor V Leiden mutation analysis was positive in 6.1% of patients. Coagulation abnormality did not differ significantly between the patients with and without SVT., Conclusions: SVT is more common in patients with necrotizing pancreatitis, suggesting that local inflammation plays a major role in its causation. Thrombophilia is seen in one third of patients with AP but does not seem to increase the risk of SVT., Competing Interests: Conflict of Interest: None
- Published
- 2018
- Full Text
- View/download PDF
49. Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients.
- Author
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Albrecht DS, Ahmed SU, Kettner NW, Borra RJH, Cohen-Adad J, Deng H, Houle TT, Opalacz A, Roth SA, Melo MFV, Chen L, Mao J, Hooker JM, Loggia ML, and Zhang Y
- Subjects
- Adult, Aged, Chronic Pain metabolism, Chronic Pain physiopathology, Cross-Sectional Studies, Female, Humans, Inflammation metabolism, Inflammation physiopathology, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Radiculopathy metabolism, Radiculopathy physiopathology, Receptors, GABA metabolism, Spinal Cord metabolism, Spinal Cord physiopathology, Spinal Nerve Roots metabolism, Spinal Nerve Roots physiopathology, Young Adult, Chronic Pain diagnostic imaging, Inflammation diagnostic imaging, Radiculopathy diagnostic imaging, Spinal Cord diagnostic imaging, Spinal Nerve Roots diagnostic imaging
- Abstract
Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. Here, we show that patients suffering from a common chronic pain disorder (lumbar radiculopathy), compared with healthy volunteers, exhibit elevated levels of the neuroinflammation marker 18 kDa translocator protein, in both the neuroforamina (containing dorsal root ganglion and nerve roots) and spinal cord. These elevations demonstrated a pattern of spatial specificity correlating with the patients' clinical presentation, as they were observed in the neuroforamen ipsilateral to the symptomatic leg (compared with both contralateral neuroforamen in the same patients as well as to healthy controls) and in the most caudal spinal cord segments, which are known to process sensory information from the lumbosacral nerve roots affected in these patients (compared with more superior segments). Furthermore, the neuroforaminal translocator protein signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.
- Published
- 2018
- Full Text
- View/download PDF
50. Single-cell mRNA cytometry via sequence-specific nanoparticle clustering and trapping.
- Author
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Labib M, Mohamadi RM, Poudineh M, Ahmed SU, Ivanov I, Huang CL, Moosavi M, Sargent EH, and Kelley SO
- Subjects
- Genotype, Humans, Neoplastic Cells, Circulating, Nucleic Acid Hybridization, Nanoparticles chemistry, RNA, Messenger genetics, Single-Cell Analysis
- Abstract
Cell-to-cell variation in gene expression creates a need for techniques that can characterize expression at the level of individual cells. This is particularly true for rare circulating tumour cells, in which subtyping and drug resistance are of intense interest. Here we describe a method for cell analysis-single-cell mRNA cytometry-that enables the isolation of rare cells from whole blood as a function of target mRNA sequences. This approach uses two classes of magnetic particles that are labelled to selectively hybridize with different regions of the target mRNA. Hybridization leads to the formation of large magnetic clusters that remain localized within the cells of interest, thereby enabling the cells to be magnetically separated. Targeting specific intracellular mRNAs enablescirculating tumour cells to be distinguished from normal haematopoietic cells. No polymerase chain reaction amplification is required to determine RNA expression levels and genotype at the single-cell level, and minimal cell manipulation is required. To demonstrate this approach we use single-cell mRNA cytometry to detect clinically important sequences in prostate cancer specimens.
- Published
- 2018
- Full Text
- View/download PDF
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