143 results on '"Y. Elamin"'
Search Results
2. BLU-945 Monotherapy and Combination With Osimertinib in Previously Treated Patients With Advanced EGFR-Mutant (EGFRm) NSCLC in Phase 1/2 SYMPHONY Study
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Y. Elamin, M. Nagasaka, E. Shum, L. Bazhenova, J. Rotow, D.R. Spigel, D.S.W. Tan, A. Zalutskaya, F. Albayya, and K.L. Reckamp
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Medicine - Published
- 2023
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3. Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer
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Charles Lu, Mehmet Altan, Apar Pataer, Tina Cascone, Annikka Weissferdt, Jianjun Zhang, Boris Sepesi, Ara A Vaporciyan, Marcelo V Negrao, Hai T Tran, Stephen G Swisher, John V Heymach, Don L Gibbons, Brett W Carter, Jack A Roth, Ferdinandos Skoulidis, Yasir Y Elamin, Xiuning Le, Wayne L Hofstetter, J Jack Lee, Bonnie S Glisson, Myrna C B Godoy, Garrett L Walsh, Jia Wu, Humam Kadara, George R Blumenschein, Heather Y Lin, Nicolas Zhou, William N William, Cheuk H Leung, Frank V Fossella, Anne S Tsao, Jonathan M Kurie, Lauren A Byers, Reza J Mehran, David C Rice, and Luisa M Solis Soto
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.Methods Tumor molecular profiles were obtained from patients with stage I–IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF was defined as any progression of primary lung cancer after neoadjuvant ICI therapy in patients without surgery, radiographic and/or biopsy-proven primary lung cancer recurrence after surgery, or death from possibly treatment-related complications or from primary lung cancer since randomization. Tumors with AGAs (n=12) were compared with tumors without AGAs and non-profiled squamous cell carcinomas (non-AGAs+NP SCC, n=20).Results With a median follow-up of 60.2 months, the overall TF rate was 34.1% (15/44). Tumor molecular profiling was retrospectively obtained in 47.7% (21/44) of patients and select AGAs were identified in 12 patients: 5 epidermal growth factor receptor (EGFR), 2 KRAS, 1 ERBB2, and 1 BRAF mutations, 2 anaplastic lymphoma kinase (ALK) and 1 RET fusions. The median time to TF in patients with AGAs was 24.7 months (95% CI: 12.6 to 40.4), compared with not reached (95% CI: not evaluable (NE)–NE) in the non-AGAs+NP SCC group. The TF risk was higher in AGAs (HR: 5.51, 95% CI: 1.68 to 18.1), and lower in former/current smokers (HR: 0.24, 95% CI: 0.08 to 0.75). The odds of major pathological response were 4.71 (95% CI: 0.49 to 45.2) times higher in the non-AGAs+NP SCC group, and the median percentage of residual viable tumor was 72.5% in AGAs compared with 33.0% in non-AGS+NP SCC tumors.Conclusions Patients with NSCLC harboring select AGAs, including EGFR and ALK alterations, have a higher risk for TF, shorter median time to TF, and diminished pathological regression after neoadjuvant ICIs. The suboptimal efficacy of neoadjuvant chemotherapy-sparing, ICI-based regimens in this patient subset underscores the importance of tumor molecular testing prior to initiation of neoadjuvant ICI therapy in patients with resectable NSCLC.
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- 2024
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4. Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights
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Sheeba J. Sujit, Muhammad Aminu, Tatiana V. Karpinets, Pingjun Chen, Maliazurina B. Saad, Morteza Salehjahromi, John D. Boom, Mohamed Qayati, James M. George, Haley Allen, Mara B. Antonoff, Lingzhi Hong, Xin Hu, Simon Heeke, Hai T. Tran, Xiuning Le, Yasir Y. Elamin, Mehmet Altan, Natalie I. Vokes, Ajay Sheshadri, Julie Lin, Jianhua Zhang, Yang Lu, Carmen Behrens, Myrna C. B. Godoy, Carol C. Wu, Joe Y. Chang, Caroline Chung, David A. Jaffray, Ignacio I. Wistuba, J. Jack Lee, Ara A. Vaporciyan, Don L. Gibbons, John Heymach, Jianjun Zhang, Tina Cascone, and Jia Wu
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Science - Abstract
Abstract While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.
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- 2024
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5. Utilization of efficient Al2O3@g-C3N4 nano sorbent for eliminated Ni (II) ions from polluted water
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Saad Aldoihi, Abdulrahman Mallah, Abdullah H. Alluhayb, Mohamed R. Elamin, Nuha Y. Elamin, Laila S. Alqarni, Mohamed Ali Ben Aissa, and Abueliz Modwi
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Al2O3@g-C3N4 ,Ni (II) adsorption kinetics ,Regeneration ,Metal ions collective removal ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
Toxic metals in water systems pose a global health risk. Thus, multifunctional water monitoring and treatment materials are indispensable. Nickel ions, a frequent heavy metal pollutant, affect ecosystem function. However, developing affordable, functional materials for efficient heavy metal removal remains problematic. This study investigates the utilization of Al2O3@g-C3N4 (AlCN) nanosorbent for adsorbing Ni (II) ions from aqueous solutions. The physicochemical analyses verify the creation of an AlCN nanosorbent with a mean size of 31.25 nm crystals and a specific surface area of 58 m2/g. Batch adsorption experiments were conducted to examine the impact of pH, initial Ni (II) concentration, and adsorbent dose on the efficiency of Ni (II) removal using the synthesized (AlCN) nanosorbent. Adding Al2O3 to g-C3N4 nanosheets increased the adsorption capacity to a maximum of 410 mg/g under ideal conditions, as demonstrated by the results. Ni (II) ions adsorption kinetics on AlCN nanosorbents follow the pseudo-second-order kinetic model with an R2 value of 0.99, surpassing the Elovich pseudo-first model. The adsorption isotherm results show that the Langmuir model fits the experimental data better than the Freundlich and Temkin models, indicating a monolayer adsorption process for the AlCN nanosorbent. In addition, the AlCN exhibited multi-elemental adsorption ability and good recyclability. These findings can nominate the fabricated composite as a candidate for water treatment.
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- 2024
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6. Real-Time Model Predictive Control Framework for a Point Absorber Wave Energy Converter With Excitation Force Estimation and Prediction.
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Abdin Y. Elamin, Addy Wahyudie, Tuanku Badzlin Hashfi, Hussain Shareef, Rachid Errouissi, Mohammad Shakeel Laghari, Marizan Mubin, and Saad Mekhilef
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- 2024
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7. A novel isatin Schiff based cerium complex: synthesis, characterization, antimicrobial activity and molecular docking studies
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Heba E. Saad, Gaber M. Abu El-Reash, Mohamed gaber, Mohamed A. Hashem, Yasmeen G. Abou El-Reash, Nuha Y. Elamin, Mohamed R. Elamin, and Yusif S. El-Sayed
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Isatin-Schiff base L2 ,Antimicrobial activity ,Cerium (III)-Schiff base complex C2 ,Molecular operating environment (MOE) ,TGA and hydrothermal reaction ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract In this work, a novel isatin-Schiff base L2 had been synthesized through a simple reaction between isatin and 2-amino-5-methylthio-1,3,4-thiadiazole. The produced Schiff base L2 was then subjected to a hydrothermal reaction with cerium chloride to produce the cerium (III)-Schiff base complex C2. Several spectroscopic methods, including mass spectra, FT-IR, elemental analysis, UV–vis, 13C-NMR, 1H-NMR, Thermogravimetric Analysis, HR-TEM, and FE-SEM/EDX, were used to completely characterize the produced L2 and C2. A computer simulation was performed using the MOE software program to find out the probable biological resistance of studied compounds against the proteins in some types of bacteria or fungi. To investigate the interaction between the ligand and its complex, we conducted molecular docking simulations using the molecular operating environment (MOE). The docking simulation findings revealed that the complex displayed greater efficacy and demonstrated a stronger affinity for Avr2 effector protein from the fungal plant pathogen Fusarium oxysporum (code 5OD4) than the original ligand. The antibacterial activity of the ligand and its Ce3+ complex were applied in vitro tests against different microorganism. The study showed that the complex was found to be more effective than the ligand.
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- 2024
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8. Ru@Co3O4@g-C3N4 as a novel adsorbent for enhanced copper and cadmium abolition
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Mohamed R. Elamin, Babiker Y. Abdulkhair, Nuha Y. Elamin, Abuzar Albadri, Mukhtar Ismail, Rafia Bakheit, Kamal K. Taha, and Abueliz Modwi
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Adsorption ,Kinetics ,Ternary composite ,Ultrasonication ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
Elimination of heavy metals from contaminated water systems is of prime distress due to their capacity to prompt toxic impact on the flora and fauna. The usage of innovative nano-engineered materials predominantly opens up smart prospects for the treatment of persistent heavy metal adulterated water resources. This study presents an ultrasonic-assisted sol-gel production of Ru@Co3O4@g-C3N4 nanostructure that was utilized to remove Cu+2 and Cd+2 ions from aqueous solutions. The X-ray diffraction investigation revealed the development of RuO2, Co2O3 and g-C3N4 phases, and the relevant elemental composition was verified by the photoelectron spectroscopy and EDX. The dispersion of the metal oxides within the nitride sheets was evidenced by scanning and transmission electron microscopy. The initial metal ions concentration, pH, and contact time effects were investigated through batch experiments. The adsorption isotherm models matched the Langmuir isotherm well, whereas the kinetics model data perfectly fitted the pseudo-second-order model. The maximum adsorption capacities of Cu+2 and Cd+2 ions on the nanocomposite Ru@Co3O4@g-C3N4 were 696.9 and 564.5 mg/g, respectively. A mechanism based on a viable covalent type of bonding developed by the delocalized -conjugated electrons of the triazine ring and functional groups were efficiently involved in the metal ions anchoring and ultimate elimination. Thus, the suitability of the Ru@Co3O4@g-C3N4 nanocomposite for eradicating heavy metals, including Cu+2 and Cd+2, was established.
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- 2024
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9. Real-world effectiveness of COVID-19 vaccines: A retrospective cohort study of vaccinated individuals in Jazan, Saudi Arabia
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Mohammed Y. Elamin, Yahya A. Maslamani, Mohammed A. Muaddi, Anwar A. Alameer, Ahmad Y. Alqassim, Abrar A. Doweri, Mutaz M. Zaylaee, Hussain Y. Rayani, Abdulaziz Y. Darraj, Yehya M. Hejri, Abdu A. Dahlan, and Ibrahim M. Gosadi
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COVID-19 ,Vaccine ,Effectiveness ,Jazan ,Saudi Arabia ,Infectious and parasitic diseases ,RC109-216 ,Public aspects of medicine ,RA1-1270 - Abstract
Background: COVID-19 (Coronavirus Disease 2019) vaccinations are a critical control measure for the coronavirus pandemic that began in 2019. Several COVID-19 vaccines have been developed, and their effectiveness will almost certainly vary. Objective: This study aimed to assess how effective two doses of the Pfizer and Oxford-AstraZeneca vaccines were in preventing SARS‐CoV‐2 infection six months after administration. Methods: This is a retrospective cohort study of adult individuals from the Jazan Region of Saudi Arabia who received their second dose of the COVID-19 vaccine [Pfizer and Oxford-AstraZeneca (ASZ)] between April and June 2021. The monitoring and follow-up period continued until the end of January 2022. Data were retrieved from the Health Electronic Surveillance Network and National Vaccination Records. Logistic regression was performed to assess the risk of COVID-19 infection among the vaccinated subjects. Results: This study included randomly enrolled 4458 participants in Jazan who received two doses of the COVID-19 vaccine during the research period. The majority of them received the Pfizer vaccine (3136/4458; 70.3%), while the remaining received the ASZ vaccine (1322/4458; 29.7%). The study participants’ mean age was 59.7 years, with a male-to-female ratio of 1.9:1.0 (2920:1538). The results showed that the Pfizer and ASZ vaccines’ protection against infection decreased from 93.2% and 90.2%, respectively, during the first three months, to 68.5% and 68.1% after a six-month interval. In the current study population, being Saudi Arabian, younger as well as having longer intervals between vaccines or crossing a 6-month period after the second vaccine dose were factors linked to higher rates of breakthrough infections. Conclusion: Our findings revealed variations in the efficacy of different COVID-19 vaccine types against COVID-19 breakthrough infections. The Pfizer (mRNA-based) vaccine was found to be relatively more effective than the ASZ (DNA-based) vaccine.
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- 2023
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10. Retrospective cohort study of thromboembolic events in systemic lupus erythematosus with or without secondary antiphospholipid syndrome and their correlation to lupus activity and dyslipidemia
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Ahmed A. G. Ibrahim, Hesham W. E. Shadi, Awab A. Y. Elamin, and Hoda E. Draz
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Antiphospholipid syndrome (APS) is one of the most frequent forms of acquired thrombophilia and is associated with an increased risk of stroke, heart attack, pulmonary embolism, and miscarriage in young women. Thirty to 40% of systemic lupus erythematosus (SLE) patients have associated APS. Patients with SLE often have abnormal plasma lipid concentrations. The study aimed to assess the prevalence of thromboembolic insults in SLE patients, with or without APS, and its correlation with disease activity and dyslipidemia. This study included one hundred three patients, seventy-five of whom had SLE without associated APS and twenty-eight had SLE associated with APS. Results Vascular affection, neurological affection, and abortion were significantly higher in SLE patients associated with APS than SLE patients without APS (39.3% vs 6.7%, 46.4% vs 14.7%, 28.6% vs 5.3%, respectively; P < 0.001). Thromboembolic insults were present in 20% of SLE patients without APS, and those patients with thromboembolism demonstrated significantly higher SLEDAI (median = 15 vs 10, P < 0.001) and TG (median = 27.5 vs 18.2, P = 0.007), respectively, than other patients of the same group. The SLEDAI score was significantly higher in SLE patients associated with APS than in SLE patients without APS (P < 0.001). Serum cholesterol and low-density lipoprotein (LDL) were significantly higher in SLE patients associated with APS (93.8 ± 25.3 mg/dl) than in SLE patients without APS (82.3 ± 19.6 mg/dl, P = 0.018; 50 ± 15.9 mg/dl, P = 0.048, respectively). Conclusions SLE patients are at significantly high risk for accelerated atherosclerosis, thromboembolism, and pregnancy loss which is multifactorial. Active disease should be well controlled. Lupus patients should be screened for aPL antibodies, and positive cases must be treated according to international guidelines. All patients with SLE should undergo lipid profile screening, and any abnormalities should be managed promptly.
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- 2023
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11. Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer
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Lingzhi Hong, Muhammad Aminu, Shenduo Li, Xuetao Lu, Milena Petranovic, Maliazurina B. Saad, Pingjun Chen, Kang Qin, Susan Varghese, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Amy Spelman, Yasir Y. Elamin, Marcelo V. Negrao, Ferdinandos Skoulidis, Carl M. Gay, Tina Cascone, Saumil J. Gandhi, Steven H. Lin, Percy P. Lee, Brett W. Carter, Carol C. Wu, Mara B. Antonoff, Boris Sepesi, Jeff Lewis, Don L. Gibbons, Ara A. Vaporciyan, Xiuning Le, J. Jack Lee, Sinchita Roy-Chowdhuri, Mark J. Routbort, Justin F. Gainor, John V. Heymach, Yanyan Lou, Jia Wu, Jianjun Zhang, and Natalie I. Vokes
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Science - Abstract
Immune checkpoint inhibitors with or without chemotherapy are now standard of care for non-small cell lung cancer. However, the benefits of combination vs sequential therapy have not been fully explored. Here, the authors analysed 1,133 patient records and show combination therapy showed increased protection against early progression, but similar overall survival.
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- 2023
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12. Brief Report: Clinical Response, Toxicity, and Resistance Mechanisms to Osimertinib Plus MET Inhibitors in Patients With EGFR-Mutant MET-Amplified NSCLC
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Kaiwen Wang, PharmD, Robyn Du, BS, Sinchita Roy-Chowdhuri, MD, Ziping T. Li, MD, Lingzhi Hong, MD, Natalie Vokes, MD, Yasir Y. Elamin, MD, Celyne Bueno Hume, MD, Ferdinandos Skoulidis, MD, PhD, Carl M. Gay, MD, PhD, George Blumenschein, MD, Frank V. Fossella, MD, Anne Tsao, MD, Jianjun Zhang, MD, PhD, Niki Karachaliou, MD, Aurora O’Brate, PhD, Claudia-Nanette Gann, MD, Jeff Lewis, MS, Waree Rinsurongkawong, PhD, J. Jack Lee, PhD, MS, DDS, Don Lynn Gibbons, MD, PhD, Ara A. Vaporciyan, MD, John V. Heymach, MD, PhD, Mehmet Altan, MD, and Xiuning Le, MD, PhD
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Resistance mechanisms ,MET ,EGFR ,NSCLC ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization. Methods: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response was assessed on the basis of Response Evaluation Criteria in Solid Tumors version 1.1. Results: From March 2016 to March 2022, 23 treatments with dual MET inhibitor and osi were identified with a total of 20 patients included. Three patients received capmatinib plus OSI after progression on crizotinib plus OSI. Median age was 64 (38–89) years old and 75% were female. MET amplification was detected by FISH in 14 patients in the tissue, NGS in 10 patients, and circulating tumor DNA in three patients. Median MET gene copy number was 13.6 (6.4–20). Overall response rate was 34.8% (eight of 23). In assessable patients, tumor shrinkage was observed in 82.4% (14 of 17). Median time on treatment was 27 months. Two of three patients responded to capmatinib plus OSI after progression on crizotinib plus OSI. Dual EGFR-MET inhibition was overall well tolerated. Two patients on crizotinib plus OSI and one pt on capmatinib plus OSI discontinued therapy due to pneumonitis. One pt discontinued crizotinib plus OSI due to gastrointestinal toxicity. Six patients were still on double TKI treatment. At disease progression to dual EGFR-MET inhibition, FISH and NGS on tumor and plasma were completed in six patients. Notable resistance mechanisms observed include acquired MET D1246H (n = 1), acquired EGFR C797S (n = 2), FGFR2 fusion (n = 1, concurrent with C797S), and EGFR G796S (n = 1, concurrent with C797S). Four patients lost MET amplification. Conclusions: Dual EGFR and MET inhibition yielded high clinical response rate after progression on OSI. Resistance mechanisms to EGFR-MET double TKI inhibition include MET secondary mutation, EGFR secondary mutation, or loss of MET amplification.
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- 2023
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13. Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial
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Jing Li, Yan Wang, Chad Tang, James Welsh, Renata Ferrarotto, Mehmet Altan, Tina Cascone, Juhee Song, Marcelo V Negrao, John V Heymach, Brett W Carter, Ferdinandos Skoulidis, Yasir Y Elamin, Xiuning Le, Caroline Chung, George R Blumenschein, Nandita Guha-Thakurta, Jeffrey S Wefel, Amol J Ghia, Debra N Yeboa, Mary Frances McAleer, Kristina D Woodhouse, Susan L McGovern, Chenyang Wang, Betty Y S Kim, Jeffrey S Weinberg, and Tina M Briere
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC.Patients and methods This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered concurrently (within 7 days). The endpoints were safety and 4-month intracranial progression-free survival (PFS).Results Thirteen patients were enrolled in the safety cohort, 10 of whom were evaluable for dose-limiting toxicities (DLTs). Median follow-up was 23 months (range 9.7–24.3 months). The median interval between systemic therapy and radiation therapy was 3 days. Only one patient had a DLT; hence, predefined stopping criteria were not met. In addition to the patient with DLT, three patients had treatment-related grade ≥3 adverse events, including elevated liver function tests, fatigue, nausea, adrenal insufficiency, and myocarditis. One patient had a confirmed influenza infection 7 months after initiation of protocol treatment (outside the DLT assessment window), leading to pneumonia and subsequent death from hemophagocytic lymphohistiocytosis. The estimated 4-month intracranial PFS rate was 70.7%.Conclusion Concurrent brain SRS with nivolumab/ipilimumab was safe for patients with active NSCLC BM. Preliminary analyses of treatment efficacy were encouraging for intracranial treatment response.
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- 2023
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14. Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study
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Maliazurina B Saad, PhD, Lingzhi Hong, MD, Muhammad Aminu, MD, Natalie I Vokes, MD, Pingjun Chen, PhD, Morteza Salehjahromi, PhD, Kang Qin, MD, Sheeba J Sujit, PhD, Xuetao Lu, PhD, Elliana Young, MS, Qasem Al-Tashi, PhD, Rizwan Qureshi, PhD, Carol C Wu, ProfMD, Brett W Carter, ProfMD, Steven H Lin, ProfMD, Percy P Lee, ProfMD, Saumil Gandhi, MD, Joe Y Chang, ProfMD, Ruijiang Li, PhD, Michael F Gensheimer, MD, Heather A Wakelee, ProfMD, Joel W Neal, MD, Hyun-Sung Lee, MD, Chao Cheng, PhD, Vamsidhar Velcheti, ProfMD, Yanyan Lou, MD, Milena Petranovic, MD, Waree Rinsurongkawong, PhD, Xiuning Le, MD, Vadeerat Rinsurongkawong, PhD, Amy Spelman, PhD, Yasir Y Elamin, MD, Marcelo V Negrao, MD, Ferdinandos Skoulidis, MD, Carl M Gay, MD, Tina Cascone, MD, Mara B Antonoff, MD, Boris Sepesi, MD, Jeff Lewis, BS, Ignacio I Wistuba, ProfMD, John D Hazle, ProfPhD, Caroline Chung, MD, David Jaffray, ProfPhD, Don L Gibbons, ProfMD, Ara Vaporciyan, ProfMD, J Jack Lee, ProfPhD, John V Heymach, ProfMD, Jianjun Zhang, MD, and Jia Wu, PhD
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Summary: Background: Only around 20–30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying cancer biology. We aimed to investigate the application of deep learning on chest CT scans to derive an imaging signature of response to immune checkpoint inhibitors and evaluate its added value in the clinical context. Methods: In this retrospective modelling study, 976 patients with metastatic, EGFR/ALK negative NSCLC treated with immune checkpoint inhibitors at MD Anderson and Stanford were enrolled from Jan 1, 2014, to Feb 29, 2020. We built and tested an ensemble deep learning model on pretreatment CTs (Deep-CT) to predict overall survival and progression-free survival after treatment with immune checkpoint inhibitors. We also evaluated the added predictive value of the Deep-CT model in the context of existing clinicopathological and radiological metrics. Findings: Our Deep-CT model demonstrated robust stratification of patient survival of the MD Anderson testing set, which was validated in the external Stanford set. The performance of the Deep-CT model remained significant on subgroup analyses stratified by PD-L1, histology, age, sex, and race. In univariate analysis, Deep-CT outperformed the conventional risk factors, including histology, smoking status, and PD-L1 expression, and remained an independent predictor after multivariate adjustment. Integrating the Deep-CT model with conventional risk factors demonstrated significantly improved prediction performance, with overall survival C-index increases from 0·70 (clinical model) to 0·75 (composite model) during testing. On the other hand, the deep learning risk scores correlated with some radiomics features, but radiomics alone could not reach the performance level of deep learning, indicating that the deep learning model effectively captured additional imaging patterns beyond known radiomics features. Interpretation: This proof-of-concept study shows that automated profiling of radiographic scans through deep learning can provide orthogonal information independent of existing clinicopathological biomarkers, bringing the goal of precision immunotherapy for patients with NSCLC closer. Funding: National Institutes of Health, Mark Foundation Damon Runyon Foundation Physician Scientist Award, MD Anderson Strategic Initiative Development Program, MD Anderson Lung Moon Shot Program, Andrea Mugnaini, and Edward L C Smith.
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- 2023
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15. USING CHATGPT TO CREATE ENGAGING PROBLEM-BASED LEARNING SCENARIOS IN ANATOMY: A STEP-BY-STEP GUIDE.
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M. H., KARRAR ALSHARIF, A. Y., ELAMIN, J. M., ALMASAAD, N. M., BAKHIT, A., ALARIFI, K. M., TAHA, W. A., HASSAN, and E., ZUMRAWI
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PROBLEM-based learning ,CHATGPT ,ANATOMY ,CRITICAL thinking ,ARTIFICIAL intelligence - Abstract
Background: Problem-based learning is widely recognized for its ability to foster active learning and critical thinking in medical education. However, creating effective problem-based learning scenarios demands a high level of expertise. Leveraging the natural language capabilities of ChatGPT, educators can now receive assistance in designing engaging anatomy problem-based learnings. Objective: This paper aims to provide a comprehensive guide on collaborating with ChatGPT to generate ideas, develop content, and create supporting materials for anatomy problem-based learning scenarios. Material and methods: Our methodology involved an analysis of literature on problem-based learning best practices and experimentation on content creation using ChatGPT. The outputs were refined based on valuable feedback obtained from both educators and students. Results: This guide emphasizes crucial aspects such as defining clear learning objectives, ensuring academic rigour, and aligning the problem-based learning scenarios with the curriculum. By harnessing ChatGPT's conversational abilities, educators can collaboratively co-create problem-based learning scenarios that are engaging and effective. Conclusion: This human-artificial intelligence collaborative approach to anatomy problem-based learning design underscores the importance of maintaining oversight over the content generated by ChatGPT. Further research is necessary to quantify the impact of ChatGPT as a supplementary resource. Purposeful integration of ChatGPT, in alignment with pedagogical goals, has the potential to enhance engagement and learning outcomes, particularly for digitally native students. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Spectrophotometric and Fluorometric Methods for the Determination of Fe(III) Ions in Water and Pharmaceutical Samples
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Ahmed Shahat, Nuha Y. Elamin, and Wesam Abd El-Fattah
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Chemistry ,QD1-999 - Published
- 2021
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17. Incidental detection of paranasal sinuses abnormalities on CT imaging of the head in Saudi adult population.
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Ali Hassan A Ali, Omar O Serhan, Mohammed H Karrar Alsharif, Abubaker Y Elamin, Sameer Al-Ghamdi, Khaled K Aldossari, Naif Alrudian, Mansour Alajmi, Bader A Alhariqi, Mohammad Mokhatrish, and Velmurugan Palanivel
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Medicine ,Science - Abstract
The paranasal sinuses are hollowed, air-filled cavities surrounding the nasal cavity. Many pathological processes affect the sinuses, but inflammatory conditions are the commonest, even in asymptomatic patients who undergo head imaging for other indications showing one or more abnormalities of the sinuses. Our research aims to determine the prevalence of incidental paranasal sinuses abnormalities seen among patients who undergo head CT scanning. In addition, it provides baseline information for further investigations required. The study was designed to evaluate all patients who underwent head CT scanning for any reason unrelated to paranasal sinuses abnormalities. 1849 cases were selected and retrospectively analyzed from the elective and emergency CT in the last nine months, from August 2020 to April 2021. In order to meet the inclusion criteria, indications for imaging must not be sinus-related. The study was conducted on 1849 cases who had undergone head CT scans for pathology, 1204 (65%) were male and 645 (35%) were female. Abnormalities of the sinuses were found in about 617 (33%) of all patients, with a higher rate in males (22.23%) than females (11.14%). In addition, these abnormalities were found in younger patients at a higher rate than in middle and old ages 19.74%, 7.19%, and 6.44%, respectively. Our findings revealed that the prevalence of paranasal sinuses abnormalities in asymptomatic Saudi patients was high (33%). Most of the affected sinuses were the maxillary. The male patients were more affected than females in all findings.
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- 2022
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18. Assessing Continuity of Adherence to Precautionary Measures for COVID-19 among Vaccinated People in Jazan, Saudi Arabia
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Anwar Alameer, Yahya Maslamani, Ibrahim M. Gosadi, Mohammed Y. Elamin, Mohammed A. Muaddi, Ahmad Y. Alqassim, Abrar Doweri, Ibrahim Namis, Fatimah Busayli, Hussam Ahmadini, Yehya Hejri, and Abdu Dahlan
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COVID-19 ,respiratory hygiene ,variants ,post-vaccination ,adherence ,prevention ,Biology (General) ,QH301-705.5 - Abstract
Background: Adherence to behavioral respiratory hygiene practices is essential in preventing the transmission of COVID-19, especially given the appearance of new variants of the COVID-19 virus. This study estimated the pre- and post-vaccination levels of adherence to COVID-19 preventive behavioral measures among vaccinated people. Methods: This cross-sectional study assessed the sociodemographics and preventive behavioral measures, and pre- and post-vaccination data, via a questionnaire. Paired t-tests and Chi-squared tests were used to assess the variation in adherence levels. Results: Of the 480 participants, 57.9% were male, and 30.4% were aged between 30 and 39 years of age. After vaccination, there was a statistically significant decline in adherence to all the assessed behavioral protective measures (p < 0.05). Being 50 years old or older, female, a healthcare worker, and a smoker were associated with higher adherence levels compared with other groups in the same categories. Conclusions: A change in the behavior of the community members regarding COVID-19 after receiving the vaccination and a reduction in adherence to respiratory hygiene practices was observed. This indicates the importance of raising awareness about the possibility of reinfection with COVID-19 despite the vaccination, and the importance of behavioral respiratory hygiene for the prevention and control of COVID-19.
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- 2023
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19. Application of Synthesized Vanadium–Titanium Oxide Nanocomposite to Eliminate Rhodamine-B Dye from Aqueous Medium
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Mohamed R. Elamin, Babiker Y. Abdulkhair, Nuha Y. Elamin, Khalid H. Ibnaouf, Hajo Idriss, Rafia Bakheit, and Abueliz Modwi
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V@TiO2 nanocomposite ,Rh-B dye removal ,removal mechanism ,regeneration ,Organic chemistry ,QD241-441 - Abstract
In this study, a V@TiO2 nanocomposite is examined for its ability to eliminate carcinogenic Rhodamine (Rh-B) dye from an aqueous medium. A simple ultrasonic method was used to produce the nanosorbent. In addition, V@TiO2 was characterized using various techniques, including XRD, HRTEM, XPS, and FTIR. Batch mode studies were used to study the removal of Rh-B dye. In the presence of pH 9, the V@TiO2 nanocomposite was able to remove Rh-B dye to its maximum extent. A correlation regression of 0.95 indicated that the Langmuir model was a better fit for dye adsorption. Moreover, the maximum adsorption capacity of the V@TiO2 nanocomposite was determined to be 158.8 mg/g. According to the thermodynamic parameters, dye adsorption followed a pseudo-first-order model. Based on the results of the study, a V@TiO2 nanocomposite can be reused for dye removal using ethanol.
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- 2022
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20. Excellent Adsorption of Dyes via MgTiO3@g-C3N4 Nanohybrid: Construction, Description and Adsorption Mechanism
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Abueliz Modwi, Mohamed R. Elamin, Hajo Idriss, Nuha Y. Elamin, Fatima A. Adam, Abuzar E. Albadri, and Babiker Y. Abdulkhair
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MgTiO3@g-C3N4 nanohybrid ,RhB dye uptake ,adsorption modeling ,removal mechanism ,Inorganic chemistry ,QD146-197 - Abstract
This report investigates the elimination of hazardous Rhodamine B dye (RhB) from an aqueous medium utilizing MgTiO3@g-C3N4 nanohybrids manufactured using a facile method. The nanohybrid MgTiO3@g-C3N4 was generated using an ultrasonic approach in the alcoholic solvent. Various techniques, including HRTEM, EDX, XRD, BET, and FTIR, were employed to describe the fabricated MgTiO3@g-C3N4 nanohybrids. RhB elimination was investigated utilizing batch mode studies, and the maximum removal was attained at pH 7.0. The RhB adsorption process is more consistent with the Langmuir isotherm model. The highest adsorption capacity of MgTiO3@g-C3N4 nanohybrids for RhB was determined to be 232 mg/g. The dye adsorption followed a pseudo-second-order model, and the parameters calculated indicated that the kinetic adsorption process was spontaneous. Using ethanol and water, the reusability of the nanomaterial was investigated, and based on the results; it can be concluded that the MgTiO3@g-C3N4 nanohybrids are easily regenerated for dye removal. The removal mechanism for the removal of RhB dye into MgTiO3@g-C3N4 nanohybrids was also investigated.
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- 2022
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21. Oncogene-specific differences in tumor mutational burden, PD-L1 expression, and outcomes from immunotherapy in non-small cell lung cancer
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Jianhua Zhang, Hao Xu, Alexandre Reuben, Brian Alexander, Jack Lee, Tina Cascone, Jianjun Zhang, Kyle G Mitchell, Marcelo V Negrao, Stephen G Swisher, John V Heymach, Don L Gibbons, Jack A Roth, Ferdinandos Skoulidis, Yasir Y Elamin, Xiuning Le, Anne Tsao, Chang-Jiun Wu, Vincent A Miller, Bonnie S Glisson, Karthikeyan Murugesan, Meagan Montesion, Garrett Frampton, Katja Schulze, Ilze Bara, Vincent Shen, Sylvia Hu, Dawen Sui, Michael E Goldberg, David S Barreto, Jacqulyne P Robichaux, Carl M Gay, Lingzhi Hong, Waree Rinsurongkawong, Vassiliki Papadimitrakopoulou, Gaurav Singal, Lee A Albacker, and David Shames
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background Non-small cell lung cancer (NSCLC) patients bearing targetable oncogene alterations typically derive limited benefit from immune checkpoint blockade (ICB), which has been attributed to low tumor mutation burden (TMB) and/or PD-L1 levels. We investigated oncogene-specific differences in these markers and clinical outcome.Methods Three cohorts of NSCLC patients with oncogene alterations (n=4189 total) were analyzed. Two clinical cohorts of advanced NSCLC patients treated with ICB monotherapy [MD Anderson (MDACC; n=172) and Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB; n=894 patients)] were analyzed for clinical outcome. The FMI biomarker cohort (n=4017) was used to assess the association of oncogene alterations with TMB and PD-L1 expression.Results High PD-L1 expression (PD-L1 ≥50%) rate was 19%–20% in classic EGFR, EGFR exon 20 and HER2-mutant tumors, and 34%–55% in tumors with ALK, BRAF V600E, ROS1, RET, or MET alterations. Compared with KRAS-mutant tumors, BRAF non-V600E group had higher TMB (9.6 vs KRAS 7.8 mutations/Mb, p=0.003), while all other oncogene groups had lower TMB (p
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- 2021
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22. Synthesis, Spectroscopic Characterization, Molecular Docking and Biological Activity of Novel Secnidazole Metal Complexes
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Wesam Abd El-Fattah and Nuha Y. Elamin
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secnidazole ,complexes ,antibacterial activity ,anticancer activity ,molecular docking ,MCF-7 ,Inorganic chemistry ,QD146-197 - Abstract
In this study, four new Secnidazole metal complexes have been synthesized through the reaction of Secnidazole drug with AuCl3, PtCl2, PdCl2, AgNO3 salts. The structures of the synthesized complexes were elucidated using elemental analysis, molar conductivity, thermal analysis, IR, 1H-NMR and UV-Vis spectroscopy. The spectroscopic results confirm that Secnidazole drug act as a bidentate ligand, coordinated to the metal ion with N3 of the imidazole ring and oxygen atom of OH group. The antimicrobial data revealed that the complexes possess a better antibacterial activity against most of the selected bacteria species than the free drug. In addition, the cytotoxic data showed that Ag-complex possesses a potent anticancer activity against MCF-7 cell line. The docking data showed that the synthesized complexes displayed a good and effective binding model against breast cancer protein (3hb5) which was confirmed by the low values of binding energy and multiple H-bonds.
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- 2022
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23. Spontaneous Adsorption and Efficient Photodegradation of Indigo Carmine under Visible Light by Bismuth Oxyiodide Nanoparticles Fabricated Entirely at Room Temperature
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Mohamed R. Elamin, Khalid H. Ibnaouf, Nuha Y. Elamin, Fatima A. Adam, Abdulrahman H. Alolayan, and Babiker Y. Abdulkhair
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bismuth oxyiodide ,sonochemical synthesis ,indigo carmine ,adsorption ,visible-light photodegradation ,Inorganic chemistry ,QD146-197 - Abstract
Bismuth oxyiodide (BiOI) is a targeted material for its relative safety and photocatalytic activity under visible light. In this study, a successful simple and energy-saving route was applied to prepare BiOI through a sonochemical process at room temperature. The characterization of the prepared BiOI was conducted by physical means. The transmission electron microscope (TEM) image showed that the BiOI comprises nanoparticles of about 20 nm. Also, the surface area of the BiOI was found to be 34.03 m2 g−1 with an energy gap of 1.835 eV. The adsorption and photocatalytic capacities of the BiOI were examined for the indigo carmine dye (IC) as a model water-pollutant via the batch experiment methodology. The solution parameters were optimized, including pH, contact time, IC concentration, and temperature. Worth mentioning that an adsorption capacity of 185 mg·g−1 was obtained from 100 mg L−1 IC solution at 25 °C within 60 min as an equilibrium time. In addition, the BiOI showed a high degradation efficiency towards IC under tungsten lamb (80 W), where 93% was removed within 180 min, and the complete degradation was accomplished in 240 min. The fabricated BiOI nanoparticles completely mineralized the IC under artificial visible light, as indicated by the total organic carbon analysis.
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- 2022
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24. An Experimental and Theoretical Study of the Optical Properties of (C2H7N4O)2BiCl5 for an Optoelectronic Application
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Hela Ferjani, Youssef Ben Smida, Damian C. Onwudiwe, Nuha Y. Elamin, Safa Ezzine, and Norah S. Almotlaq
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chlorobismuthate(III) ,Hirshfield surface analysis ,BFDH simulation ,spectroscopic studies ,GGA-PBE ,band structure ,Inorganic chemistry ,QD146-197 - Abstract
This study explores the electronic properties of (C2H7N4O)2BiCl5 using the density functional theory (DFT) method, which was compared with the experimental data. The band structure of the compound indicated that it is a direct semiconductor with a band gap energy of 3.54 eV, which was comparable with the value (3.20 eV) obtained experimentally from the UV–vis spectroscopy. The density of state study showed that the conduction band was formed mainly by Bi 6p, C 2p, and N 2p states, while the valence band was formed mainly by Cl 2p, O 2p, and N 2p states. Hirshfeld surface analysis and enrichment ratio (E) were further used to investigate and quantify the intermolecular interactions within the compound. These studies established that the most important role in the stability of the structure of this crystalline material was provided by hydrogen bonding and π–π stacking interactions. The crystalline morphology of the compound was determined using BFDH simulation, based on the single-crystal structure result. Furthermore, Fourier transform infrared spectroscopy (FTIR) was used to study the vibrational modes of carbamoyl-ganidinium cations. The charge transfer process within the anionic chains of [BiCl5]∝, studied using photoluminescence spectroscopy, resulted in a broad emission band with two positions of maxima centered at 336 and 358 nm. This work offers a good understanding of the optical, structural, as well as the electrical properties of (C2H7N4O)2BiCl5, which are necessary in its applications in areas such as multifunctional magnetic, optoelectronic, and photonic systems.
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- 2022
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25. Green Synthesis of Lead Oxide Nanoparticles, Characterization and Adsorption Study for Removal of Malachite Green Dye
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Nuha Y. Elamin, Egbal Eltom, and Rasha Ramadan
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Ocean Engineering - Abstract
In this study lead oxide nanoparticles were synthesized by using ecofriendly and non-toxic Morus rubra extract. The obtained lead oxide nanoparticles were characterized by XRD, SEM, EDX, BET and FTIR techniques. Powder X-ray diffraction analysis revealed that synthesized PbO nanoparticles had crystallite structure of high purity. SEM survey shows that the obtained nanoparticles having in general uniform particle distribution and the particle sizes vary within the range of 22.4 to 29.2nm. As established by EDX to confirm the presence of lead and oxygen, the weight percentage of the latter was (71.5 % Pb and 28.5% O), respectively. FT-IR spectra exhibit a sharp peak at 439.38 and 595.46 cm−1 attributed to PbO vibration, confirming the formation of PbO nanoparticles. The effectiveness of PbO nanostructures for removing indigo carmine (MG) dye from an aqueous solution is demonstrated in this article. , the MG dye uptake and adsorption processes were investigated using a PbO sorbent. The maximum adsorption capacity and contact time were optimized which corresponding to 41.3 mg. g-1 and 60min respectively.
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- 2023
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26. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial
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Tina Cascone, Cheuk H. Leung, Annikka Weissferdt, Apar Pataer, Brett W. Carter, Myrna C. B. Godoy, Hope Feldman, William N. William, Yuanxin Xi, Sreyashi Basu, Jing Jing Sun, Shalini S. Yadav, Frank R. Rojas Alvarez, Younghee Lee, Aditya K. Mishra, Lili Chen, Monika Pradhan, Haiping Guo, Ansam Sinjab, Nicolas Zhou, Marcelo V. Negrao, Xiuning Le, Carl M. Gay, Anne S. Tsao, Lauren Averett Byers, Mehmet Altan, Bonnie S. Glisson, Frank V. Fossella, Yasir Y. Elamin, George Blumenschein, Jianjun Zhang, Ferdinandos Skoulidis, Jia Wu, Reza J. Mehran, David C. Rice, Garrett L. Walsh, Wayne L. Hofstetter, Ravi Rajaram, Mara B. Antonoff, Junya Fujimoto, Luisa M. Solis, Edwin R. Parra, Cara Haymaker, Ignacio I. Wistuba, Stephen G. Swisher, Ara A. Vaporciyan, Heather Y. Lin, Jing Wang, Don L. Gibbons, J. Jack Lee, Nadim J. Ajami, Jennifer A. Wargo, James P. Allison, Padmanee Sharma, Humam Kadara, John V. Heymach, and Boris Sepesi
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Abstract
Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8+ T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129.)
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- 2023
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27. IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC
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Sonia A. Patel, Monique B. Nilsson, Yan Yang, Xiuning Le, Hai T. Tran, Yasir Y. Elamin, Xiaoxing Yu, Fahao Zhang, Alissa Poteete, Xiaoyang Ren, Li Shen, Jing Wang, Seyed Javad Moghaddam, Tina Cascone, Michael Curran, Don L. Gibbons, and John V. Heymach
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Cancer Research ,Oncology - Abstract
Purpose: Patients with advanced non–small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary EGFR mutations or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI resistance are limited as anti-PD-1/PD-L1 inhibitors typically display minimal benefit. Given that IL6 is associated with worse outcomes in patients with NSCLC, we investigate whether IL6 in part contributes to this immunosuppressed phenotype. Experimental Design: We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC to investigate the effects of IL6 on the tumor microenvironment and the combined efficacy of IL6 inhibition and anti-PD-1 therapy. Corresponding in vitro studies used EGFR-mutant human cell lines and clinical specimens. Results: We identified that EGFR-mutant tumors which have oncogene-independent acquired resistance to EGFR-TKIs were more mesenchymal and had markedly enhanced IL6 secretion. In EGFR-mutant GEMMs, IL6 depletion enhanced activation of infiltrating natural killer (NK)- and T-cell subpopulations and decreased immunosuppressive regulatory T and Th17 cell populations. Inhibition of IL6 increased NK- and T cell–mediated killing of human osimertinib-resistant EGFR-mutant NSCLC tumor cells in cell culture. IL6 blockade sensitized EGFR-mutant GEMM tumors to PD-1 inhibitors through an increase in tumor-infiltrating IFNγ+ CD8+ T cells. Conclusions: These data indicate that IL6 is upregulated in EGFR-mutant NSCLC tumors with acquired EGFR-TKI resistance and suppressed T- and NK-cell function. IL6 blockade enhanced antitumor immunity and efficacy of anti-PD-1 therapy warranting future clinical combinatorial investigations.
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- 2023
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28. Evaluation of physicochemical and biological properties of SnO2 and Fe doped SnO2 nanoparticles
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Nuha Y. Elamin, T. Indumathi, and E. Ranjith Kumar
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Process Chemistry and Technology ,Materials Chemistry ,Ceramics and Composites ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials - Published
- 2023
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29. Responsiveness to immune checkpoint inhibitors versus other systemic therapies in RET-aberrant malignancies
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Jessica Lee, Vivek Subbiah, Shuang Liu, Jason Roszik, David Hong, Funda Meric-Bernstam, John Heymach, Ramona Dadu, Kenneth Hess, Le Huang, Aparna Hegde, Alexander Y Andreev-Drakhlin, Maria Cabanillas, Mimi I Hu, Naifa L Busaidy, Steven I Sherman, Elizabeth G Grubbs, Siraj M Ali, Yasir Y Elamin, George R Simon, George R Blumenschein, Jr, and Vassiliki A Papadimitrakopoulou
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Purpose The receptor tyrosine kinase rearranged during transfection (RET) can be oncogenically activated by gene fusions or point mutations. Multikinase inhibitors such as cabozantinib, lenvatinib and vandetanib have demonstrated activity in RET-dependent malignancies, and selective RET inhibitors (Selpercatinib and Pralsetinib) are in clinical trials. However, the responsiveness of RET-dependent malignancies to immune checkpoint inhibitors (ICIs) is unknown. We compared the time to treatment discontinuation (TTD) for ICI versus non-ICI therapy in patients with malignancies harbouring activating RET mutations or fusions (RET+).Methods A retrospective review of all RET+ patients who were referred to the phase I clinical trials programme at the University of Texas MD Anderson Cancer Center was conducted. TTD was estimated using Kaplan-Meier analysis. Multivariate analysis using the Cox proportional hazard model was performed to identify independent risk factors of treatment discontinuation.Results Of 70 patients who received systemic therapy for RET+ malignancies, 20 (28.6%) received ICI and 50 (71.4%) received non-ICI therapy. Non-ICI therapy was associated with decreased risk for treatment discontinuation compared with ICI in the overall population (HR=0.31; 95% CI 0.16–0.62; p=0.000834) and in patients with RET point mutations (HR=0.13; 95% CI 0.04–0.45; p=0.00134). In patients with RET fusions, non-ICI therapy was associated with a non-statistically significant decreased risk of treatment discontinuation (HR=0.59; 95% CI 0.25–1.4; p=0.24). ICI therapy and a diagnosis other than medullary thyroid cancer (MTC) were independent risk factors for treatment discontinuation.Conclusion Our study supports the prioritisation of non-ICI over ICI therapy in patients with RET+ tumours.
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- 2020
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30. Is there a misuse of computed tomography in the diagnostic workup of headache? A retrospective record-based study in secondary health-care facility in Saudi Arabia
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Ali Hassan A. Ali, Sameer Al-Ghamdi, Mohammed H Karrar, Saud A Alajmi, Osama S Almutairi, Ahmed M Aldalbahi, Yazeed M Alotaibi, Sattam A Alruwaili, and Abubaker Y Elamin
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Computed tomography ,primary headache ,secondary headache ,Medicine - Abstract
Introduction: Headache disorders are one of the most prevalent global public-health problems that require placing high demand on health-care Services. Since it is one of the most frequent complaints in clinical practice worldwide, it causes a considerable burden in terms of the social cost. The study aimed to give a guide for the decision on the utilization of computed tomography (CT) in the diagnostic workup and identify if patients require neurological imaging (CT) for proper diagnosis or not. Material s and Methods: The study was carried out in the Radiology Department in King Khalid Hospital, Al Kharj, Saudi Arabia from October 15, 2016, to February 15, 2017. A retrospective record-based study conducted using the documented CT reports in the files of patients whom were referred to the radiology department complaining of any type of a headache. Results: The data included 210 patients 51% were males and 49% were females. The patients were distributed into age groups; the mean age was 38.46 standard deviation ± 13.56. Among Saudi population, the etiology of headache was varying; the most prevalent type of headache was tension headache 25.71% of the total headache patients followed by cluster 25.24% and the migraine with the lowest proportionality. The majority of the patients' headache pain was mild 60%. Moreover, the CT reports for most of the patients were normal. Spearman Correlation test was used to see if there is a significance in using the CT for any patient who comes with symptoms including headache, and the results have shown that there is no association and clinical significance in using the CT for patients with headache without suspecting other clinical condition (P = 0.177). Conclusion: Headache disorders must be on the public-health agenda. Tension, migraine, and cluster-type headaches represent the majority of primary headaches. Statistically no significance or need to obtain CT if there are no life-threatening conditions expected or trauma presented.
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- 2018
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31. How do young Saudi men prefer to receive fertility information? A population: Based survey in Al Kharj
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Ali Hassan A Ali, Mohammed H Karrar Alsharif, Abubaker Y Elamin, Salman S Bin Ofisan, Ali Y Alali, Abdulrahman Mesfer Aldawsari, Ammar H Alenazi, Bandar Suliman S AlSultan, and Talal Abdullah Alharbi
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- 2022
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32. Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC)
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Toomey, Cathy E. Richards, Yasir Y. Elamin, Aoife Carr, Kathy Gately, Shereen Rafee, Mattia Cremona, Emer Hanrahan, Robert Smyth, Daniel Ryan, Ross K. Morgan, Susan Kennedy, Lance Hudson, Joanna Fay, Kenneth O’Byrne, Bryan T. Hennessy, and Sinead
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Shp2 ,PTPN11 ,lung cancer ,somatic mutations ,PI3K signalling pathway ,MAPK signalling pathway ,cancer therapy ,targeted therapy ,anti-cancer drugs - Abstract
PTPN11 encodes the SHP2 protein tyrosine phosphatase that activates the mitogen-activated protein kinase (MAPK) pathway upstream of KRAS and MEK. PTPN11/Shp2 somatic mutations occur frequently in Juvenile myelomonocytic leukaemia (JMML); however, the role of mutated PTPN11 in lung cancer tumourigenesis and its utility as a therapeutic target has not been fully addressed. We applied mass-spectrometry-based genotyping to DNA extracted from the tumour and matched the normal tissue of 356 NSCLC patients (98 adenocarcinomas (LUAD) and 258 squamous cell carcinomas (LUSC)). Further, PTPN11 mutation cases were identified in additional cohorts, including TCGA, Broad, and MD Anderson datasets and the COSMIC database. PTPN11 constructs harbouring PTPN11 E76A, A72D and C459S mutations were stably expressed in IL-3 dependent BaF3 cells and NSCLC cell lines (NCI-H1703, NCI-H157, NCI-H1299). The MAPK and PI3K pathway activation was evaluated using Western blotting. PTPN11/Shp2 phosphatase activity was measured in whole-cell protein lysates using an Shp2 assay kit. The Shp2 inhibitor (SHPi) was assessed both in vitro and in vivo in a PTPN11-mutated cell line for improved responses to MAPK and PI3K targeting therapies. Somatic PTPN11 hotspot mutations occurred in 4/98 (4.1%) adenocarcinomas and 7/258 (2.7%) squamous cells of 356 NSCLC patients. Additional 26 PTPN11 hotspot mutations occurred in 23 and 3 adenocarcinomas and squamous cell carcinoma, respectively, across the additional cohorts. Mutant PTPN11 significantly increased the IL-3 independent survival of Ba/F3 cells compared to wildtype PTPN11 (p < 0.0001). Ba/F3, NCI-H1703, and NCI-H157 cells expressing mutant PTPN11 exhibited increased PTPN11/Shp2 phosphatase activity and phospho-ERK1/2 levels compared to cells expressing wildtype PTPN11. The transduction of the PTPN11 inactivating mutation C459S into NSCLC cell lines led to decreased phospho-ERK, as well as decreased phospho-AKT in the PTPN11-mutated NCI-H661 cell line. NCI-H661 cells (PTPN11-mutated, KRAS-wild type) were significantly more sensitive to growth inhibition by the PI3K inhibitor copanlisib (IC50: 13.9 ± 4.7 nM) compared to NCI-H1703 (PTPN11/KRAS-wild type) cells (IC50: >10,000 nM). The SHP2 inhibitor, in combination with the PI3K targeting therapy copanlisib, showed no significant difference in tumour development in vivo; however, this significantly prevented MAPK pathway induction in vitro (p < 0.0001). PTPN11/Shp2 demonstrated the in vitro features of a driver oncogene and could potentially sensitize NSCLC cells to PI3K inhibition and inhibit MAPK pathway activation following PI3K pathway targeting.
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- 2023
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33. Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance
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Yanshuo Chu, Enyu Dai, Yating Li, Guangchun Han, Guangsheng Pei, Davis R. Ingram, Krupa Thakkar, Jiang-Jiang Qin, Minghao Dang, Xiuning Le, Can Hu, Qing Deng, Ansam Sinjab, Pravesh Gupta, Ruiping Wang, Dapeng Hao, Fuduan Peng, Xinmiao Yan, Yunhe Liu, Shumei Song, Shaojun Zhang, John V. Heymach, Alexandre Reuben, Yasir Y. Elamin, Melissa P. Pizzi, Yang Lu, Rossana Lazcano, Jian Hu, Mingyao Li, Michael Curran, Andrew Futreal, Anirban Maitra, Amir A. Jazaeri, Jaffer A. Ajani, Charles Swanton, Xiang-Dong Cheng, Hussein A. Abbas, Maura Gillison, Krishna Bhat, Alexander J. Lazar, Michael Green, Kevin Litchfield, Humam Kadara, Cassian Yee, and Linghua Wang
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
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34. Supplementary Figure S4 from IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC
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John V. Heymach, Don L. Gibbons, Michael Curran, Tina Cascone, Seyed Javad Moghaddam, Jing Wang, Li Shen, Xiaoyang Ren, Alissa Poteete, Fahao Zhang, Xiaoxing Yu, Yasir Y. Elamin, Hai T. Tran, Xiuning Le, Yan Yang, Monique B. Nilsson, and Sonia A. Patel
- Abstract
IL-6 modulates expression of NK receptor and their ligands in EGFR mutant tumors.
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- 2023
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35. Proposed Model for Remote Maintenance of CCTV Cameras
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Mohammed Y. Elamin, Ashraf Gasim Elsid Abdalla, and Mahir M. Sharif
- Abstract
A data center is a physical facility in which an organization stores its critical applications and data. In our paper, the researchers developed an Android model for surveillance CCTV system maintenance and fault identification. The descriptive analytic approach and object-oriented systems analysis and design approach were used. The Unified Modeling Language (UML) was used as a tool in analysis and design, and Java was used as a programming language to develop an Android model to maintain CCTV faults. Image freezing, incorrect time and date, and video delay were resolved. It has been developed an Android model that works on smart phones to monitor and maintain surveillance CCTV systems. This model allows users to view faults reports and fix camera faults, such as (image freezing, camera image delay, and incorrect time on the camera) in surveillance CCTV systems from anywhere that has Internet access.
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- 2022
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36. Controlling Surveillance Systems and PTZ Cameras from a Mobile Device
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Ashraf Gasim Elsid Abdalla and Mohammed Y. Elamin
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General Medicine - Abstract
A data center is a physical facility that organizations use to house their critical applications and data. An application delivery controller, router, switch, firewall, storage system, and server make up the design for the data center. Data security in the data center is critical due to these components' role in storing and managing critical business data and applications. An Android application has therefore been developed that can be used on smart phones to monitor and follow the performance of the data center camera monitoring system. Surveillance cameras in the data center allows the data center manager to monitor employees, machines, and all data center facilities from his office via his mobile phone, or even when he is out of the office, and to view a report of faults and maintenance to ensure the efficiency of the system. Using the application, the engineer can also control the cameras by panning and zooming in on the camera images in the data center, playback previous recordings of cameras, and review fault reports to find out the malfunctions of the monitoring system from anywhere with an Internet connection.
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- 2022
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37. Mesoporous Sn@TiO2 nanostructures as excellent adsorbent for Ba ions in aqueous solution
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Lotfi Khezami, Nuha Y. Elamin, Mohamed Bououdina, A. Modwi, Kamal K. Taha, and M.S. Amer
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Aqueous solution ,Materials science ,Process Chemistry and Technology ,Langmuir adsorption model ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,law.invention ,symbols.namesake ,Adsorption ,X-ray photoelectron spectroscopy ,Chemical engineering ,law ,Materials Chemistry ,Ceramics and Composites ,symbols ,Calcination ,Crystallite ,Fourier transform infrared spectroscopy ,Mesoporous material - Abstract
Efficient adsorption of Ba ions was achieved using Sn@TiO2 nanocomposite generated by ultrasonication process with subsequent calcination at 300 °C. X-ray diffraction, nitrogen adsorption-desorption isotherm, X-ray photoelectron spectroscopy, Fourier transformer infra-red, and scanning/transmission electron microscopy analyses were performed to probe the structural and textural features of the adsorbent powder. The XPS, FTIR, and EDX analyses confirmed the Sn doping into TiO2 host lattice. Some interesting features, including the increase of crystallite size and lattice parameters, were attained due to the successful Sn incorporation into the TiO2 host, as indicated further by XRD analysis. The sorption results fitted the Langmuir isotherm model and the kinetic data complied with the pseudo-second-order kinetics. The adsorption process improved markedly above the pHzc due to the electrostatic attraction between the negatively charged Sn@TiO2 particles’ surface and the positively charged Ba ions. The achieved high-performance mesoporous Sn@TiO2 nanostructures for the adsorption of Ba2+ could be potentially utilized to remove other toxic metal cations.
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- 2022
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38. Data from Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results
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Neil D. Gross, Bonnie S. Glisson, Maura L. Gillison, Andrew G. Sikora, J. Jack Lee, Faye M. Johnson, Jeffrey N. Myers, Adam S. Garden, Amy C. Hessel, Carla L. Warneke, Danice K. Torman, Yasir Y. Elamin, Jack Phan, Ryan P. Goepfert, Jason M. Johnson, Katherine A. Hutcheson, Maria L. Rubin, Diana Bell, and Renata Ferrarotto
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Purpose:In oropharyngeal squamous cell carcinoma (OPC), high CD8+ tumor-infiltrating lymphocyte (CD8+TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8+TIL density, safety, and efficacy in patients with OPC.Patients and Methods:Patients with newly diagnosed stage II–IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8+TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes.Results:Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8+TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 0.97; 95% CI: −1.07–2.28). In each group, 6 patients (43%, 95% CI: 17.66–71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8+TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8+TIL change in patients with a MPR was seen (P = 0.059; 95% CI: −0.33–3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence.Conclusions:Durvalumab + tremelimumab did not increase CD8+TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.
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- 2023
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39. Supplementary Tables from Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results
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Neil D. Gross, Bonnie S. Glisson, Maura L. Gillison, Andrew G. Sikora, J. Jack Lee, Faye M. Johnson, Jeffrey N. Myers, Adam S. Garden, Amy C. Hessel, Carla L. Warneke, Danice K. Torman, Yasir Y. Elamin, Jack Phan, Ryan P. Goepfert, Jason M. Johnson, Katherine A. Hutcheson, Maria L. Rubin, Diana Bell, and Renata Ferrarotto
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Supplementary Tables
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- 2023
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40. Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non–Small-Cell Lung Cancer Reveals EGFR Mutations to Be Associated With Longer Overall Survival
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Brian De, Ahsan S. Farooqi, Kyle G. Mitchell, Ethan B. Ludmir, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, J. Jack Lee, Stephen G. Swisher, Don L. Gibbons, Jianjun Zhang, Xiuning Le, Yasir Y. Elamin, Daniel R. Gomez, Matthew S. Ning, Steven H. Lin, Zhongxing Liao, Joe Y. Chang, Ara A. Vaporciyan, John V. Heymach, Mara B. Antonoff, and Saumil J. Gandhi
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Cancer Research ,Oncology - Abstract
PURPOSE Local consolidative therapy (LCT) for patients with synchronous oligometastatic non–small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients. METHODS We identified all patients presenting between 2000 and 2017 with stage IV non–small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis. RESULTS Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. TP53 mutations were identified in 40 of 78 (55%), KRAS in 32 of 95 (34%), EGFR in 24 of 109 (22%), and STK11 in nine of 77 (12%). At median follow-up of 96 months, median OS and PFS were 26 (95% CI, 23 to 31) months and 11 (95% CI, 9 to 13) months, respectively. On multivariable analysis, patients with EGFR mutations had lower mortality risk (hazard ratio [HR], 0.53; 95% CI, 0.29 to 0.98; P = .044) compared with wild-type patients, and patients with STK11 mutations had higher risk of progression or mortality (HR, 2.32; 95% CI, 1.12 to 4.79; P = .023) compared with wild-type patients. TP53 and KRAS mutations were not associated with OS or PFS. Among 71 patients with known EGFR mutational status who received comprehensive LCT, EGFR mutations were associated with lower mortality compared with wild-type (HR, 0.45; 95% CI, 0.22 to 0.94; P = .032). CONCLUSION When compared with wild-type patients, those with EGFR and STK11 mutations had longer OS and shorter PFS, respectively. EGFR mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.
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- 2023
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41. Yttrium oxide-doped ZnO for effective adsorption of basic fuchsin dye: equilibrium, kinetics, and mechanism studies
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Nuha Y. Elamin, Abdullah Sulaiman Al-Ayed, M. A. Ben Aissa, A. Modwi, B. Mustafa, Lotfi Khezami, and Kamal K. Taha
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Environmental Engineering ,Materials science ,Kinetics ,Doping ,Oxide ,chemistry.chemical_element ,Yttrium ,BASIC FUCHSIN ,chemistry.chemical_compound ,Adsorption ,Chemical engineering ,chemistry ,Environmental Chemistry ,General Agricultural and Biological Sciences ,Mechanism (sociology) - Published
- 2021
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42. Optimal Control of a Supercapacitor Energy Storage System for Smoothing Wave Output Power
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Abdin Y. Elamin and Addy Wahyudie
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- 2022
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43. Quantitative Evaluation of Grey Matter Volume of Thalamus in Patients with Depression on Magnetic Resonance Imaging: Segmentation Study
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Khalid M. Taha, Hosam Eldeen Elsadig Gasmalla, Abubaker Y. Elamin, Juman M. Almasaad, Nagi M. Bakhit, and Mohammed H. Karrar Alsharif
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Purpose: The thalamus, a part of the diencephalon, controls emotion and memory; any thalamic lesion may lead to impairments in recall and recognition. There is no concrete proof that depression is the only mental condition in which thalamic abnormalities are present. Therefore, the purpose of this study was to determine whether patients with depression had any structural changes in their thalamic grey matter volume. Methods: The thalamic grey matter volume was measured in 50 patients with depression (25 males, mean age = 24 ± 5.02 years) and 50 sex- and-age-matched controls (25 males, mean age = 24 ± 5.28 years) using BrainSuite automated segmentation of the T1-weighted magnetic resonance images obtained using Magnetization Prepared Rapid Acquisition. Between-group and sex-based comparisons were made using Student’s t-test. Results: The mean grey matter volume of the right and left thalamus was 5.98 ± 7.03 cm3 and 6.21 ± 7.68 cm3 in patients, respectively, and 2.18 ± 4.74 cm3on the right side and 2.15 ± 4.87 cm3 on the left side in the controls (p < 0.05). The female subjects had relatively greater mean thalamic grey matter volumes on both sides (patients: right = 6.47 ± 4.17 cm3, left = 6.77 ± 4.30 cm3; controls: right = 3.25 ± 6.55 cm3, left = 3.13 ± 6.77 cm3; p < 0.05). Conclusion: The volume of thalamic grey matter is increased in patients with depression, which is more pronounced in female patients. There is also a possible association between depression and right-sided volume reduction.
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- 2022
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44. Limited Benefit from the Addition of Immunotherapy to Chemotherapy in TKI-Refractory EGFR-Mutant Lung Adenocarcinoma
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Lingzhi Hong, Whitney E. Lewis, Monique Nilsson, Sonia Patel, Susan Varghese, Melvin J. Rivera, Robyn R. Du, Pingjun Chen, Haley N. Kemp, Waree Rinsurongkawong, Simon Heeke, Amy R. Spelman, Yasir Y. Elamin, Marcelo V. Negrao, Boris Sepesi, Don L. Gibbons, J. Jack Lee, Jia Wu, Natalie I. Vokes, John V. Heymach, Jianjun Zhang, and Xiuning Le
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Cancer Research ,Oncology ,lung adenocarcinoma ,EGFR ,tyrosine kinase inhibitors ,immunotherapy ,chemotherapy - Abstract
Background: The benefit of chemotherapy combined with immunotherapy in EGFR-mutant lung adenocarcinoma (LUAD) patients whose tumor developed resistance to EGFR tyrosine kinase inhibitors (TKIs) is not thoroughly investigated. The goal of this retrospective cohort study is to assess the clinical efficiency of immunotherapy alone or in combination with chemotherapy in a real-world setting. Methods: This retrospective cohort study enrolled LUAD patients with EGFR sensitive mutations whose tumor had acquired resistance to EGFR TKIs and received systemic treatment with chemotherapy (chemo; n = 84), chemotherapy combined with immunotherapy (chemoIO; n = 30), chemotherapy plus bevacizumab with or without IO (withBev; n = 42), and IO monotherapy (IO-mono; n = 22). Clinical progression-free survival (PFS) and overall survival (OS) were evaluated. Associations of clinical characteristics with outcomes were assessed using univariable and multi-covariate Cox Proportional Hazards regression models. Results: A total of 178 patients (median age = 63.3; 57.9% females) with a median follow-up time of 42.0 (Interquartile range: 22.9–67.8) months were enrolled. There was no significant difference in PFS between chemoIO vs. chemo groups (5.3 vs. 4.8 months, p = 0.8). Compared to the chemo group, patients who received withBev therapy trended towards better PFS (6.1 months vs. 4.8; p = 0.3; HR 0.79; 95% CI: 0.52–1.20), while patients treated with IO-mono had inferior PFS (2.2 months; p = 0.001; HR 2.22; 95% CI: 1.37–3.59). Furthermore, PD-L1 level was not associated with PFS benefit in the chemoIO group. Patients with EGFR-mutant LUAD with high PD-L1 (≥50%) had shorter PFS (5.8 months) than non-EGFR/ALK LUAD patients who received chemoIO (12.8 months, p = 0.002; HR 0.22; 95% CI: 0.08–0.56) as first-line treatment. Chemotherapy-based therapy rendered similar benefit to patients with either EGFR exon19 deletion vs. L858R in the LUAD. Conclusions: This retrospective analysis revealed that immunotherapy provided limited additional benefit to chemotherapy in TKI-refractory EGFR-mutant LUAD. Chemotherapy alone or combined with bevacizumab remain good choices for patients with actionable EGFR mutations.
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- 2022
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45. Visceral leishmaniasis-hepatitis B/C coinfections: a rising necessity to triage patients for treatment
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Abubakr O. A. Adam, Mohamed M. M. Dafalla, Hatim A. A. Mohammed, Mohamed Y. Elamin, Brima M. Younis, Mona E. E. Elfaki, Ahmed M. Musa, Ahmed M. Elhassan, and Eltahir A. G. Khalil
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Medicine - Abstract
BACKGROUND AND OBJECTIVES: Visceral leishmaniasis (VL) is a life-threatening infection caused by Leishmania species. In Sudan, VL is caused by L donovani. Most drugs used to treat VL, especially pentavalent antimony compounds (sodium stibogluconate, SSG), are potentially hepatotoxic. A number of fatal catastrophes happened because patients with VL-hepatitis B/C coinfection were indiscriminately treated with SSG in settings where VL and viral hepatitis coexist. This study aimed to study biochemical and hematological parameters of patients with VL-hepatitis B/C coinfections with the aim to modify treatment protocols to reduce coinfection-added morbidity and mortality. DESIGN AND SETTINGS: This was a prospective analytical, hospital-based, and case-controlled study. The study was done at Kassab Hospital and Professor Elhassan Centre for tropical medicine during the period of February 2008 to April 2013. MATERIALS AND METHODS: Following informed consent by the participants, 78 parasitologically confirmed VL patients with either hepatitis B or C or both and 528 sex- and age-unmatched VL patients without hepatitis B/C coinfection (control group) were enrolled sequentially. Diagnosis of hepatitis B or C was made using immunochromatographic test kits and confirmed by an enzyme-linked immunosorbent assay. RESULTS: VL patients with hepatitis B/C coinfections had significantly increased levels of AST, ALT, and total bilirubin compared to the control group (P=.0001 for all), with significantly decreased levels of albumin and platelets counts (P=.0029 for both). CONCLUSION: VL-hepatitis B/C coinfections are an emerging entity that needs anti-leishmanial treatment modification. Alternative treatments like paromomycin and amphotericin B (AmBisome) could be reserved for these patients.
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- 2014
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46. Adsorption Behavior of Congo Red onto Barium-Doped ZnO Nanoparticles: Correlation between Experimental Results and DFT Calculations
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Mohamed Ali Ben Aissa, A. Modwi, Lotfi Khezami, Seyfeddine Rahali, Mahamadou Seydou, and Nuha Y. Elamin
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Materials science ,Doping ,Infrared spectroscopy ,02 engineering and technology ,Surfaces and Interfaces ,Interaction energy ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,Congo red ,chemistry.chemical_compound ,Adsorption ,Chemical bond ,chemistry ,Chemisorption ,Electrochemistry ,Physical chemistry ,General Materials Science ,Density functional theory ,0210 nano-technology ,Spectroscopy - Abstract
Ba-loaded ZnO nanoparticles (Ba/ZnO) were obtained by the co-precipitation process and employed as a sorbent for Congo Red (C32H22N6Na2O6S2) dye (CR). Physicochemical parameters such as particle size, pH, and contact time were checked to characterize the adsorption process. The maximum adsorption capacity of Ba/ZnO NPs for CR (1614.26 mg/g) proves its potential utility in the elimination of CR dye from wastewater. The adsorption mechanism was studied via infrared spectroscopy and density functional theory calculations. The geometrical parameters and electronic properties of the CR-Ba/ZnO complex, particularly the interaction energy, the density of states, and the charge transfer, highlighted the Ba-ion mediation in the chemical bond formation between CR and the surface. The interaction between CR and Ba-doped ZnO has found to show strong chemisorption with charge transfer between the SO3- group and adsorbed Ba2+ ion on the surface.
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- 2021
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47. Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer
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Paul Armstrong, Bryan T. Hennessy, Joanna Fay, Yasir Y. Elamin, Aoife Carr, Katherine M. Sheehan, M. Janusz Mezynski, Clare Morgan, Liam Grogan, Stephen F. Madden, Mattia Cremona, Elaine W. Kay, Jennifer McAuley, Ciara Holohan, Oscar S. Breathnach, Patrick G. Morris, Shereen Rafee, Julie Workman, Sinead Toomey, and Angela M. Farrelly
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0301 basic medicine ,MAPK/ERK pathway ,Signalling pathway activation ,Receptor, ErbB-2 ,HER2-positive gastric cancer ,Treatment resistance ,Lapatinib ,PI3K ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Targeted therapies ,Trastuzumab ,Stomach Neoplasms ,Somatic mutations ,Cell Line, Tumor ,medicine ,Humans ,ERBB3 ,skin and connective tissue diseases ,neoplasms ,PI3K/AKT/mTOR pathway ,Copanlisib ,business.industry ,Research ,Cancer ,General Medicine ,medicine.disease ,MAPK ,030104 developmental biology ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,Growth inhibition ,business ,medicine.drug - Abstract
Background Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in overcoming trastuzumab resistance is unclear. Methods Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients. A panel of gastric cell lines (N87, OE19, ESO26, SNU16, KATOIII) were profiled for anti-proliferative response to the PI3K inhibitor copanlisib and the MEK1/2 inhibitor refametinib alone and in combination with anti-HER2 therapies. Results Patients with HER2-positive GC had significantly poorer overall survival compared to HER2-negative patients (15.9 months vs. 35.7 months). Mutations in PIK3CA were only identified in HER2-negative tumours, while ERBB-family mutations were identified in HER2-positive and HER2-negative tumours. Copanlisib had anti-proliferative effects in 4/5 cell lines, with IC50s ranging from 23.4 (N87) to 93.8 nM (SNU16). All HER2-positive cell lines except SNU16 were sensitive to lapatinib (IC50s 0.04 µM–1.5 µM). OE19 cells were resistant to trastuzumab. The combination of lapatinib and copanlisib was synergistic in ESO-26 and OE-19 cells (ED50: 0.83 ± 0.19 and 0.88 ± 0.13, respectively) and additive in NCI-N87 cells (ED50:1.01 ± 0.55). The combination of copanlisib and trastuzumab significantly improved growth inhibition compared to either therapy alone in NCI-N87, ESO26 and OE19 cells (p Conclusions PI3K or MEK inhibition alone or in combination with anti-HER2 therapy may represent an improved treatment strategy for some patients with HER2-positive GC, and warrants further investigation in a clinical trial setting.
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- 2021
48. Pluronic f127 encapsulated titanium dioxide nanoparticles: Evaluation of physiochemical properties for biological applications
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Nuha Y. Elamin, T. Indumathi, and E. Ranjith Kumar
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Materials Chemistry ,Physical and Theoretical Chemistry ,Condensed Matter Physics ,Spectroscopy ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials - Published
- 2023
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49. New Actions on Actionable Mutations in Lung Cancers
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Xiuning Le, Yasir Y. Elamin, and Jianjun Zhang
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Cancer Research ,Oncology - Abstract
Actionable mutations refer to DNA alterations that, if detected, would be expected to affect patients’ response to treatments [...]
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- 2023
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50. Abstract LB123: Poorer outcomes in EGFR L858R-driven NSCLC treated with osimertinib may be addressed with novel combination of BLU-945 and osimertinib
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Yasir Y. Elamin, Tyler Rouskin-Faust, Nicole Zhang, Teresa Green, Aditya Dhande, Brenton G. Mar, John V. Heymach, and Chiara Conti
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Cancer Research ,Oncology - Abstract
Background: Osimertinib, a 3rd-generation (gen) EGFR tyrosine kinase inhibitor (TKI), is standard of care in front-line (1L) patients with advanced EGFR mutant NSCLC; however, not all subgroups may benefit equally. In the phase 3 FLAURA study, patients with exon 19 deletions (ex19del) had a median progression-free survival (mPFS) of 21.4 months (mo); patients with L858R had a shorter mPFS of 14.4 mo. Poorer outcomes with L858R have also been reported with other 3rd-gen TKIs aumolertinib and lazertinib. These patients are a potential poor-risk subgroup for these therapies. Here, we explored outcomes of patients with L858R-driven NSCLC using real-world datasets (RWDs), analyzed potential contributors to poorer outcomes, including co-mutation incidence and osimertinib potency for each mutation, and report preclinical proof of concept of combination treatment BLU-945, an investigational next-gen L858R inhibitor, with osimertinib. Methods: Two large RWDs were analyzed for survival outcomes in 1L osimertinib-treated patients with ex19del or L858R from MD Anderson Cancer Center (MDACC; n=105) and the clinical-genomic Guardant INFORM database (EGFR ctDNA baseline positive; n=1386). IC50s of osimertinib on EGFR mutations and wildtype were determined in BaF3 cells. Preclinical studies of combination BLU-945 and osimertinib were performed in L858R-driven BaF3 xenograft models. Results: Both RWDs confirmed poorer prognosis for 1L osimertinib-treated patients with L858R vs ex19del. MDACC cohort showed a 12-mo PFS rate of 63% for L858R (n=45) vs 82% for ex19del (n=60); mPFS was immature. Guardant INFORM cohort (ctDNA baseline positive) had a median time-to-treatment discontinuation of 8 mo for L858R (n=517) and 11.4 mo for ex19del (n=869), P=0.003. Poor prognosis factors (including TP53 mutations and co-mutation number) were not significantly different between L858R and ex19del; both had a similar number of off-target mutations in post-osimertinib samples. Strong association was found between osimertinib cellular IC50 and osimertinib clinical trial outcomes (mPFS). Osimertinib exhibited most clinical and cellular activity on ex19del, followed by L858R, then G719X, and then exon 20 insertions. BLU-945 in combination with osimertinib in a BaF3 L858R xenograft model demonstrated a longer duration of response vs osimertinib monotherapy. Conclusions: In both RWDs, 1L osimertinib-treated patients with L858R-driven NSCLC had poorer outcomes vs ex19del, consistent with osimertinib’s weaker activity on L858R. Preclinically, BLU-945 in combination with osimertinib increased L858R inhibition, resulting in more durable antitumor activity in L858R xenografts vs osimertinib alone, supporting rationale for combination treatment in patients with L858R mutations. This combination is being evaluated in 1L patients with L858R in the SYMPHONY study (NCT04862780). Citation Format: Yasir Y. Elamin, Tyler Rouskin-Faust, Nicole Zhang, Teresa Green, Aditya Dhande, Brenton G. Mar, John V. Heymach, Chiara Conti. Poorer outcomes in EGFR L858R-driven NSCLC treated with osimertinib may be addressed with novel combination of BLU-945 and osimertinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB123.
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- 2023
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