115 results on '"Sharaf R"'
Search Results
2. MA09.07 Genomic Landscape and Clinical Outcomes With Immune Checkpoint Inhibitors in NF1-Mutant NSCLC
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Negrao, M., primary, Schmidt, S., additional, Sui, D., additional, Sharaf, R., additional, Kemp, H., additional, Lewis, W., additional, Bristow, C., additional, Frampton, G., additional, Lee, J., additional, Heymach, J., additional, Gibbons, D., additional, Albacker, L., additional, and Skoulidis, F., additional
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- 2021
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3. SO-20 The landscape of homologous recombination deficiency in colorectal cancer
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Ahsan, M., Bar-Mashiah, A., Webster, E., Qazi, M., Levi, S., Perez, L., Brewer, J., Frey, M., and Sharaf, R.
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- 2023
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4. Cascade testing für erbliche Tumorerkrankungen: Eine Meta-Analyse
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Lackner, A, additional, Li, X, additional, Kahn, R, additional, Baltich, Nelson B, additional, Krinsky, H, additional, Mei, E, additional, Badiner, N, additional, Caputo, T.A, additional, Holcomb, K, additional, Chapman-Davis, E, additional, Nitecki, R, additional, Rauh-Hain, J.A, additional, Sharaf, R, additional, and Frey, M.K, additional
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- 2020
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5. Cascade genetic testing for hereditary cancer syndromes: A systematic review and meta-analysis
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Li, X., primary, Kahn, R.M., additional, Lackner, A.I., additional, Nelson, B. Baltich, additional, Krinsky, H., additional, Mei, E., additional, Badiner, N., additional, Holcomb, K.M., additional, Chapman-Davis, E., additional, Nitecki, R., additional, Rauh-Hain, J.A., additional, Sharaf, R., additional, and Frey, M.K., additional
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- 2020
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6. Cascade genetic testing: What are the quality of life implications for at-risk relatives undergoing genetic testing?
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Kahn, R.M., primary, Krinsky, H., additional, Chervenak, J., additional, Anderson, S.R., additional, Lipkin, K., additional, Tubito, F., additional, Pires, M., additional, Blank, S.V., additional, Sharaf, R., additional, Chapman-Davis, E., additional, Caputo, T.A., additional, Holcomb, K.M., additional, and Frey, M.K., additional
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- 2020
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7. Barriers to uptake of oncologic cascade genetic testing: Results of a prospective cohort study
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Kahn, R.M., primary, Chapman-Davis, E., additional, Krinsky, H., additional, Anderson, S.R., additional, Caputo, T.A., additional, Tubito, F., additional, Pires, M., additional, Tkachuk, K., additional, Sharaf, R., additional, Offit, K., additional, Holcomb, K.M., additional, Lipkin, K., additional, and Frey, M.K., additional
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- 2020
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8. Quality of the oncologic family health history in a gynecologic oncology clinic
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Krinsky, H., primary, Lackner, A.I., additional, Cagino, K., additional, Gamble, C.R., additional, Kahn, R.M., additional, Chapman-Davis, E., additional, Sharaf, R., additional, Lipkin, K., additional, Caputo, T.A., additional, Holcomb, K.M., additional, and Frey, M.K., additional
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- 2020
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9. Distress and anxiety associated with identifying germline cancer-associated mutations with cascade genetic testing
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Kahn, R.M., primary, Chapman-Davis, E., additional, Krinsky, H., additional, Lipkin, K., additional, Anderson, S.R., additional, Tubito, F., additional, Pires, M., additional, Sharaf, R., additional, Blank, S.V., additional, Caputo, T.A., additional, Holcomb, K.M., additional, and Frey, M.K., additional
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- 2020
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10. Vulvar squamous cell carcinoma: Comprehensive genomic profiling of HPV(+) versus HPV(–) forms reveals a different set of potentially actionable biomarkers
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Williams, E.A., primary, Werth, A.J., additional, Sharaf, R., additional, Montesion, M., additional, Shah, N., additional, Sokol, E.S., additional, Pavlick, D.C., additional, Danziger, N., additional, Killian, J.K., additional, Lin, D.I., additional, Miller, V.A., additional, Ross, J.S., additional, Tse, J.Y., additional, and Elvin, J.A., additional
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- 2020
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11. An Interesting Case of Fish Spawning in An Overcrowded Nursery Pond
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Tripathi, S D, Sharaf, R K, and BioStor
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- 1976
12. HIV post-treatment control despite plasma viral evolution and dual infection
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Li, J., primary, Etemad, B., additional, Namazi, G., additional, Wen, Y., additional, Jilg, N., additional, Esmaeilzadeh, E., additional, Zhang, X., additional, Sharaf, R., additional, Brumme, Z., additional, and Kearney, M., additional
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- 2019
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13. Dilip Kumar: An Auteur Actor
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Sharaf Rehman
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howard becker ,dilip kumar ,film studies ,art and culture ,sociology of work ,film and culture ,Ethnology. Social and cultural anthropology ,GN301-674 ,Sociology (General) ,HM401-1281 - Abstract
Dilip Kumar has been praised for his sublime dialog delivery, for his restrained gestures, and for his measured and controlled underplay of emotions in tragic stories as well as in light-hearted comedies. His debut in 1944 with Jwar Bhata (Ebb and Tide) met with less-than-flattering reviews. So did the next three films until his 1948 film, Jugnu (Firefly), which brought him recognition and success. Unlike his contemporaries such as Raj Kapoor and Dev Anand, who propelled their careers by launching their own production companies, Dilip Kumar relied on his talent, his unique approach to characterization, and his immersion in the projects he undertook. In the course of his career that spanned six decades, Kumar made only 62 films. However, his work is a textbook for other actors that followed. Not only did he bring respectability to a profession that had been shunned by the upper classes in India as a profession for “pimps and prostitutes,” but he also elevated film-acting and filmmaking to an academic discipline, making him worthy of the title ‘Professor Emeritus of Acting’. Rooted in the theoretical framework of Howard S. Becker’s work on the “production of culture” and “doing things together,” this paper discusses Kumar’s approach to acting, character development, and the level of his involvement and commitment to each of his projects. The author of this article argues that more than the creative control as a producer or a director, it is the artistic involvement and commitment of the main actors that shape great works of art in cinema. Dilip Kumar demonstrated it repeatedly.
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- 2021
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14. Online INS/GPS integration with a radial basis function neural network
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Sharaf, R., primary, Noureldin, A., additional, Osman, A., additional, and El-Sheimy, N., additional
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- 2005
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15. INS/GPS data fusion technique utilizing radial basis functions neural networks.
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Noureldin, A., Sharaf, R., Osman, A., and El-Sheimy, N.
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- 2004
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16. On the design of an electronic mosquito: design and analysis of the micro-needle.
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Sharaf, R., Aggarwal, P., Kaler, K.V.I.S., and Badawy, W.
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- 2003
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17. The Trolley Problem Revisited. An Exploratory Study
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Sharaf Rehman and Joanna Dzionek‑Kozłowska
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decision making ,Trolley Problem ,inconsistency of choices ,Business ethics ,HF5387-5387.5 - Abstract
Recent studies by cognitive scientists demonstrate that people’s choices are more complex than the image provided by rational choice theory, and consistency of choice is not a characteristic to be expected in real-life situations. This exploratory paper attempts to isolate three variables in relation to decision making. Working with a sample (N=70) of university students in the U.S, and using the three variants of the Trolley Problem, the subjects’ responses are used to identify the similarities and differences based on the three dimensions. The participants were asked to respond to three hypothetical situations regarding a runaway trolley. Their decision in the first scenario could save a person’s life or let him be run over by the trolley. In the second scenario, their decision could either let one person die and save five lives or save one life and let five people be killed. These two scenarios require pulling a lever to switch the trolley from one track to another. The third scenario requires pushing an obese person in front of the runaway trolley to stop it from killing five persons. The paper presents the findings on the three variables: gender, age, and relational status.
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- 2018
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18. The control of HIV after antiretroviral medication pause (CHAMP) study: Posttreatment controllers identified from 14 clinical studies
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Aga, E., Mitsuyasu, R., Deeks, S.G., Schooley, R.T., Smith, D.M., Henry, K., Acosta, E.P., Jacobson, J.M., Li, J.Z., Walker, B.D., Sharaf, R., Sneller, M.C., Skiest, D., Mehraj, V., Gianella, S., Volberding, P., Hecht, F.M., Margolis, D., Mellors, J.W., Gandhi, R.T., Collier, A.C., Routy, J.-P., Fajnzylber, J.M., Bosch, R.J., Hartogensis, W., Little, S.J., Namazi, G., Kuritzkes, D.R., Chun, T.-W., Connick, E., Gulick, R.M., and Tebas, P.
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3. Good health - Abstract
Background. HIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized. Methods. Posttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks. Viral load and CD4 + cell dynamics were compared between posttreatment controllers and noncontrollers. Results. Of the 67 posttreatment controllers identified, 38 initiated ART during early HIV infection. Posttreatment controllers were more frequently identified in those treated during early versus chronic infection (13% vs 4%, P < .001). In posttreatment controllers with weekly viral load monitoring, 45% had a peak posttreatment interruption viral load of ≥1000 copies/mL and 33% had a peak viral load ≥10 000 copies/mL. Of posttreatment controllers, 55% maintained HIV control for 2 years, with approximately 20% maintaining control for ≥5 years. Conclusions. Posttreatment control was more commonly identified amongst early treated individuals, frequently characterized by early transient viral rebound and heterogeneous durability of HIV remission. These results may provide mechanistic insights and have implications for the design of trials aimed at achieving HIV remission.
19. INS/GPS data fusion technique utilizing radial basis functions neural networks
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Noureldin, A., primary, Sharaf, R., additional, Osman, A., additional, and El-Sheimy, N., additional
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20. Computational prediction and experimental validation associating FABP-1 and pancreatic adenocarcinoma with diabetes
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Pai Reetesh, Montgomery Kelli D, Butte Atul J, Sharaf Ravi N, Dudley Joel T, and Pasricha Pankaj J
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background Pancreatic cancer, composed principally of pancreatic adenocarcinoma (PaC), is the fourth leading cause of cancer death in the United States. PaC-associated diabetes may be a marker of early disease. We sought to identify molecules associated with PaC and PaC with diabetes (PaC-DM) using a novel translational bioinformatics approach. We identified fatty acid binding protein-1 (FABP-1) as one of several candidates. The primary aim of this pilot study was to experimentally validate the predicted association between FABP-1 with PaC and PaC with diabetes. Methods We searched public microarray measurements for genes that were specifically highly expressed in PaC. We then filtered for proteins with known involvement in diabetes. Validation of FABP-1 was performed via antibody immunohistochemistry on formalin-fixed paraffin embedded pancreatic tissue microarrays (FFPE TMA). FFPE TMA were constructed using148 cores of pancreatic tissue from 134 patients collected between 1995 and 2002 from patients who underwent pancreatic surgery. Primary analysis was performed on 21 normal and 60 pancreatic adenocarcinoma samples, stratified for diabetes. Clinical data on samples was obtained via retrospective chart review. Serial sections were cut per standard protocol. Antibody staining was graded by an experienced pathologist on a scale of 0-3. Bivariate and multivariate analyses were conducted to assess FABP-1 staining and clinical characteristics. Results Normal samples were significantly more likely to come from younger patients. PaC samples were significantly more likely to stain for FABP-1, when FABP-1 staining was considered a binary variable. Compared to normals, there was significantly increased staining in diabetic PaC samples (p = 0.004) and there was a trend towards increased staining in the non-diabetic PaC group (p = 0.07). In logistic regression modeling, FABP-1 staining was significantly associated with diagnosis of PaC (OR 8.6 95% CI 1.1-68, p = 0.04), though age was a confounder. Conclusions Compared to normal controls, there was a significant positive association between FABP-1 staining and PaC on FFPE-TMA, strengthened by the presence of diabetes. Further studies with closely phenotyped patient samples are required to understand the true relationship between FABP-1, PaC and PaC-associated diabetes. A translational bioinformatics approach has potential to identify novel disease associations and potential biomarkers in gastroenterology.
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- 2011
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21. Helicobacter pylori: a poor man's gut pathogen?
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Khalifa Mohammed, Sharaf Radwa, and Aziz Ramy
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Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Abstract Helicobacter pylori is one of the human pathogens with highest prevalence around the world; yet, its principal mode of transmission remains largely unknown. The role of H. pylori in gastric disease and cancer has not been established until the end of the 20th century. Since then, its epidemiology has been extensively studied, and an accruing body of literature suggests that not all humans are equally at risk of infection by this gut pathogen. Here, we briefly review the different epidemiological aspects of H. pylori infection with emphasis on those factors related to human poverty. The epidemiology of H. pylori infection is characterized by marked differences between developing and developed countries, notably among children. In addition, congruent lines of evidence point out to socioeconomic factors and living standards as main determinants of the age-dependent acquisition rate of H. pylori, and consequently its prevalence. These data are alarming in the light of the changing global climate and birth rate, which are expected to change the demography of our planet, putting more children at risk of H. pylori and its complications for years to come.
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- 2010
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22. Gitelman's not-so-benign syndrome.
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Pachulski RT, Lopez F, and Sharaf R
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- 2005
23. Considering screening for hereditary cancer syndromes at the time of obstetrical prenatal carrier screening.
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Perez L, Dioun S, Primiano M, Blank SV, Lipkin S, Ahsan MD, Brewer J, Fowlkes RK, Abdul-Rahman O, Hou J, Wright JD, Kang HJ, Sharaf R, Prabhu M, and Frey MK
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- 2024
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24. Disparities in Elective Spine Surgery for Medicaid Beneficiaries: A Systematic Review.
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Reddy A, Mumtaz M, Sharaf R, Tabarestani A, and Mederos C
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Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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25. Bidirectional relationship between pancreatic cancer and diabetes mellitus: a comprehensive literature review.
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Sapoor S, Nageh M, Shalma NM, Sharaf R, Haroun N, Salama E, Pratama Umar T, Sharma S, and Sayad R
- Abstract
Pancreatic cancer (PC) is a fatal malignant disease. It is well known that the relationship between PC and type 2 diabetes mellitus (T2DM) is a complicated bidirectional relationship. The most important factors causing increased risks of pancreatic cancer are hyperglycaemia, hyperinsulinemia, pancreatitis, and dyslipidemia. Genetics and the immune system also play an important role in the relationship between diabetes mellitus and pancreatic cancer. The primary contributors to this association involve insulin resistance and inflammatory processes within the tumour microenvironment. The combination of diabetes and obesity can contribute to PC by inducing hyperinsulinemia and influencing leptin and adiponectin levels. Given the heightened incidence of pancreatic cancer in diabetes patients compared to the general population, early screening for pancreatic cancer is recommended. Diabetes negatively impacts the survival of pancreatic cancer patients. Among patients receiving chemotherapy, it reduced their survival. The implementation of a healthy lifestyle, including weight management, serves as an initial preventive measure to mitigate the risk of disease development. The role of anti-diabetic drugs on survival is controversial; however, metformin may have a positive impact, especially in the early stages of cancer, while insulin therapy increases the risk of PC., Competing Interests: The authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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26. Incidence of Postoperative Infection Following Simultaneous Bilateral Knee Arthroplasty: A Systematic Review and Meta-Analysis.
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Reda B and Sharaf R
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Total knee arthroplasty is one of the most common orthopedic procedures. Simultaneous bilateral knee arthroplasty involves performing total knee arthroplasty on both knees in a single anesthetic session. This systematic review and meta-analysis followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. A primary search was performed using PubMed, EBSCO, Scopus, Web of Science, Clarivate, and Google Scholar databases. Quantitative data synthesis was performed using MedCalc® Statistical Software version 20.115 to determine the pooled prevalence of the infection among patients who underwent simultaneous bilateral knee arthroplasty. The Newcastle-Ottawa Scale was used to assess study quality. We included 30 studies in our quantitative data synthesis, with a total population of 118,502 patients (237,004 knees). The pooled prevalence of superficial infection, deep infection, and unspecified surgical site infection was estimated to be 0.86% (95% confidence interval: 0.62-1.13%), 0.84% (95% confidence interval: 0.64-1.05%), and 1.18% (95% confidence interval: 0.45-2.27%), respectively. There was significant heterogeneity (I2 >50%) in all analyses, and inspection of funnel plots revealed a symmetrical distribution of plotted data. We found that the infection rates following simultaneous bilateral knee arthroplasty were relatively low but heterogeneous, as the data showed marked variability. Superficial infections were more common than deep infections; however, there was a small difference in their prevalence. Furthermore, the reliability of our findings was limited owing to significant heterogeneity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Reda et al.)
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- 2024
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27. A Retrospective Genomic Landscape of 661 Young Adult Glioblastomas Diagnosed Using 2016 WHO Guidelines for Central Nervous System Tumors.
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Haberberger JF, Pegram W, Britt N, Schiavone K, Severson E, Sharaf R, Albacker LA, Williams E, Lechpammer M, Hemmerich A, Lin D, Huang RSP, Hiemenz M, Elvin J, Graf R, Lesser G, Kram D, Strowd R, Bi WL, Ramkissoon LA, Cohen MB, Reddy P, Creeden J, Ross JS, Alexander BM, and Ramkissoon SH
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- Humans, Young Adult, Retrospective Studies, Mutation, Neoplasm Recurrence, Local, Genomics methods, Glioblastoma diagnosis, Glioblastoma genetics, Central Nervous System Neoplasms
- Abstract
The authors present a cohort of 661 young adult glioblastomas diagnosed using 2016 WHO World Health Organization Classification of Tumors of the Central Nervous System, utilizing comprehensive genomic profiling (CGP) to explore their genomic landscape and assess their relationship to currently defined disease entities. This analysis explored variants with evidence of pathogenic function, common copy number variants (CNVs), and several novel fusion events not described in literature. Tumor mutational burden (TMB) mutational signatures, anatomic location, and tumor recurrence are further explored. Using data collected from CGP, unsupervised machine-learning techniques were leveraged to identify 10 genomic classes in previously assigned young adult glioblastomas. The authors relate these molecular classes to current World Health Organization guidelines and reference current literature to give therapeutic and prognostic descriptions where possible., (© The Author(s) 2023. Published by Oxford University Press.)
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- 2024
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28. Comparative Genomic Analysis and Clinical Outcomes of BRAF-mutated Advanced Biliary Tract Cancers.
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Tang TY, Nichetti F, Kaplan B, Lonardi S, Pietrantonio F, Salvatore L, Vivaldi C, Rimassa L, de Braud F, Rizzato MD, Pavlick D, Chu R, Danner De Armas A, Sharaf R, Sokol E, Rodon Ahnert J, Ross JS, Javle M, and Niger M
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- Humans, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins p21(ras) genetics, Mutation, Bile Ducts, Intrahepatic pathology, Genomics, Bile Duct Neoplasms genetics, Biliary Tract Neoplasms drug therapy, Biliary Tract Neoplasms genetics, Biliary Tract Neoplasms pathology, Cholangiocarcinoma drug therapy, Cholangiocarcinoma genetics, Cholangiocarcinoma pathology
- Abstract
Purpose: BRAF mutations are rare in biliary tract cancers (BTC), but are of interest given the recent developments in targeted therapy for BTC. We investigated the clinical outcomes in a cohort of BRAF-mutant advanced BTC treated with first-line chemotherapy. Furthermore, we investigated the genomic landscape of BRAF class I, II, and III mutations in the intrahepatic cholangiocarcinoma (iCCA) subgroup of BTC., Experimental Design: We analyzed two nonoverlapping cohorts. We examined the genomic landscape of BRAF-mutated iCCA in a "genomic cohort" [187 class I, 82 class II, 113 class III BRAF mutants and 8,026 wildtype (WT)]. We also analyzed median progression-free survival (PFS) and overall survival (OS) on first-line chemotherapy in a separate multi-institutional "clinical cohort" of patients with BTC (including iCCA and extrahepatic cholangiocarcinoma (eCCA) and gallbladder cancer; 41 class I, 32 class II+III BRAF mutants and 1,042 WT)., Results: In the entire BTC clinical cohort, the median PFS was shorter for class I [HR, 2.11 (P < 0.001)] and class II+III [HR, 1.72 (P = 0.007)] as compared with BRAF WT. OS was also shorter in class I [HR, 2.04 (P = 0.011)] and class II+III [HR, 1.86 (P = 0.002)] as compared with BRAF WT. In the iCCA subgroup, class I alterations were mutually exclusive with FGFR2, IDH1/2, ERBB2, and KRAS mutations. Class II+III mutations appear to be mutually exclusive with FGFR2 and KRAS., Conclusions: In BTC, all classes of BRAF mutations are associated with a worse prognosis. BRAF mutations occur in 5% of iCCA subgroup and may be mutually exclusive with other targetable mutations., (©2023 American Association for Cancer Research.)
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- 2023
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29. Letter: Laser Interstitial Thermal Therapy for First-Line Treatment of Surgically Accessible Recurrent Glioblastoma: Outcomes Compared With a Surgical Cohort.
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Mehkri Y, Sharaf R, Reddy A, and Lucke-Wold B
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- Humans, Neoplasm Recurrence, Local surgery, Lasers, Magnetic Resonance Imaging, Treatment Outcome, Glioblastoma surgery, Hyperthermia, Induced, Laser Therapy, Brain Neoplasms surgery
- Published
- 2023
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30. Viral and host mediators of non-suppressible HIV-1 viremia.
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Mohammadi A, Etemad B, Zhang X, Li Y, Bedwell GJ, Sharaf R, Kittilson A, Melberg M, Crain CR, Traunbauer AK, Wong C, Fajnzylber J, Worrall DP, Rosenthal A, Jordan H, Jilg N, Kaseke C, Giguel F, Lian X, Deo R, Gillespie E, Chishti R, Abrha S, Adams T, Siagian A, Dorazio D, Anderson PL, Deeks SG, Lederman MM, Yawetz S, Kuritzkes DR, Lichterfeld MD, Sieg S, Tsibris A, Carrington M, Brumme ZL, Castillo-Mancilla JR, Engelman AN, Gaiha GD, and Li JZ
- Subjects
- Humans, Male, Female, Viremia, Proviruses genetics, Proviruses metabolism, CD4-Positive T-Lymphocytes, RNA, Viral, Viral Load, HIV-1 genetics, HIV Seropositivity, HIV Infections drug therapy
- Abstract
Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as 'producer proviruses', and those that did not as 'non-producer proviruses'. Non-suppressible viremia arose from expanded clones of producer proviruses that were significantly larger than the genome-intact proviral reservoir of ART-suppressed individuals. Integration sites of producer proviruses were enriched in proximity to the activating H3K36me3 epigenetic mark. CD4
+ T cells from participants with NSV demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, participants with NSV showed significantly lower HIV-specific CD8+ T cell responses compared with untreated viremic controllers with similar viral loads. We identified potential critical host and viral mediators of NSV that may represent targets to disrupt HIV-1 persistence., (© 2023. The Author(s).)- Published
- 2023
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31. A cost analysis of medical students applying to neurological surgery residency: An analysis of the Texas STAR database.
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Mehkri Y, Pierzchajlo N, Kemeness C, Hey G, Sharaf R, Reddy A, Neil ZD, Sayed F, Gendreau J, and Lucke-Wold B
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- Humans, Pandemics, Prospective Studies, Costs and Cost Analysis, Internship and Residency, Students, Medical, COVID-19 epidemiology
- Abstract
Introduction: Medical Students applying to neurosurgery residency programs incur substantial costs associated with interviews, away rotations, and application fees. However, few studies have compared expenses prior to and during the COVID-19 pandemic. This study evaluates the financial impact of COVID-19 on the neurosurgery residency application and identifies strategies that may alleviate the financial burden of prospective neurosurgery residents., Methods: The TEXAS STAR database was surveyed for applicants of neurosurgical residency programs during the COVID-19 pandemic (2021) and post-pandemic (2022). 66 applicants for the 2021 application cycle and 50 applicants for the 2022 application cycle completed the survey. We compared application fees, away rotations cost, interview cost, and total expenses as reported by the neurosurgery applicants of the 2021 and 2022 application cycle. A Shapiro-Wilk test was used to test for data normality, and a Mann-Whitney U-Test was used to compare costs during the 2021 and 2022 neurosurgery application cycle., Results: There was a statistically significant reduction in total expenses in 2021 vs 2022 ($3,934 vs $9,860). Interview and away rotation expenses decreased in 2021 vs 2022 (interview expenses $786 vs $4511, away rotation $1,083 vs $3,000, p < 0.001). Application fee expenses were not different between 2021 and 2022. The greatest reduction in application cost ($11,908) was seen in the South for 2021., Conclusions: The COVID-19 pandemic significantly reduced total fees associated with the neurosurgical residency application. Virtual platforms in place of in-person interviews could lessen the financial burden on applicants and alleviate socioeconomic barriers in the neurosurgical application process after COVID-19., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)
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- 2023
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32. A Rare Case of Vaginal Atresia in an Adolescent Girl Presenting With Abdominal Pain.
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Alotaibi S, Alotaibi O, Sharaf R, Qaheri R, and Alshamrani R
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Vaginal atresia, an infrequent congenital anomaly characterized by the absence or underdevelopment of the vaginal canal, presents significant complexities in pediatric and adolescent gynecological practice. Its diverse range of clinical presentations, including primary amenorrhea and cyclic abdominal discomfort, creates diagnostic challenges, highlighting the need for timely intervention to relieve symptoms and preserve future reproductive health. This case underscores the essential role of a collaborative, multidisciplinary approach involving pediatricians, gynecologists, and surgeons in ensuring comprehensive care and optimizing patient outcomes. In this report, we present the case of a 10-year-old female who initially presented with chronic abdominal pain, which had been occurring intermittently over the course of several months. This ultimately led to the diagnosis of hematometra secondary to vaginal atresia. Utilizing magnetic resonance imaging, we confirmed the diagnosis without exposing the patient to radiation, prioritizing her safety. A successful surgery was performed to create a working vaginal canal. The patient received careful postoperative care, and we closely followed her progress to support a smooth recovery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alotaibi et al.)
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- 2023
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33. A pan-sarcoma landscape of telomeric content shows that alterations in RAD51B and GID4 are associated with higher telomeric content.
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Sharaf R, Jin DX, Grady J, Napier C, Ebot E, Frampton GM, Albacker LA, Thomas DM, and Montesion M
- Abstract
Tumor cells need to activate a telomere maintenance mechanism, enabling limitless replication. The bulk of evidence supports that sarcomas predominantly use alternative lengthening of telomeres (ALT) mechanism, commonly associated with alterations in ATRX and DAXX. In our dataset, only 12.3% of sarcomas harbored alterations in these genes. Thus, we checked for the presence of other genomic determinants of high telomeric content in sarcomas. Our dataset consisted of 13555 sarcoma samples, sequenced as a part of routine clinical care on the FoundationOne®Heme platform. We observed a median telomeric content of 622.3 telomeric reads per GC-matched million reads (TRPM) across all samples. In agreement with previous studies, telomeric content was significantly higher in ATRX altered and POT1 altered sarcomas. We further observed that sarcomas with alterations in RAD51B or GID4 were enriched in samples with high telomeric content, specifically within uterus leiomyosarcoma for RAD51B and soft tissue sarcoma (not otherwise specified, nos) for GID4, Furthermore, RAD51B and POT1 alterations were mutually exclusive with ATRX and DAXX alterations, suggestive of functional redundancy. Our results propose a role played by RAD51B and GID4 in telomere elongation in sarcomas and open research opportunities for agents aimed at targeting this critical pathway in tumorigenesis., (© 2023. Springer Nature Limited and Centre of Excellence in Genomic Medicine Research, King Abdulaziz University.)
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- 2023
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34. The Effect of Sleep Quality and Mental Health on Academic Performance Among the Medical Students of King Abdulaziz University.
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Yaghmour KA, Alhmyri SM, Alhmyri BM, Sharaf R, Alasmari MA, and Almilabi MM
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Background: Sleep quality has an important role in brain functioning and development. Affected sleep quality and mental health can negatively affect the academic performance of college students., Objective: To assess the effect of sleep quality and mental health on the academic performance of medical students at King Abdulaziz University, Jeddah, Saudi Arabia., Methods: We conducted a cross-sectional study among medical students at King Abdulaziz University. The dependent variable was the current grade point average (GPA). For the independent variables, two validated tools were used in the study: the Pittsburgh Sleep Quality Index (PSQI) for sleep assessment; and the Depression, Anxiety and Stress Scale (DASS-21) for mental health assessment., Results: A total of 382 responses were analyzed. The majority of students (86.6%) had GPAs greater than 3.75/5, while only 1% of the sample had a GPA lower than 2.75/5. The PSQI showed a median and interquartile range of (9, 6-11). Normal DASS-21 represented the majority as follows: depression at 67%, anxiety at 63.1%, and stress at 82.2%. In the statistical analyses, sleep quality, depression, anxiety, and stress were not statistically significant with the student's GPA., Conclusion: Low levels of sleep quality were found among medical students in our study. While sleep quality and mental health status did not show an effect on the GPA of the medical students, lower sleep quality was significantly correlated with increased scores of depression, anxiety, and stress. Our findings mandate interventions directed at improving sleep quality among medical students., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yaghmour et al.)
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- 2023
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35. Pan-Cancer Analysis of Copy-Number Features Identifies Recurrent Signatures and a Homologous Recombination Deficiency Biomarker to Predict Poly (ADP-Ribose) Polymerase Inhibitor Response.
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Moore JA, Chen KT, Madison R, Newberg JY, Fleischmann Z, Wang S, Sharaf R, Murugesan K, Fendler BJ, Hughes J, Schrock AB, Hegde PS, Oxnard GR, Fabrizio D, Frampton GM, Antonarakis ES, Sokol ES, and Jin DX
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- Male, Female, Humans, Ribose therapeutic use, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Recombinational DNA Repair, Biomarkers, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Antineoplastic Agents therapeutic use
- Abstract
Purpose: Copy-number (CN) features reveal the molecular state of cancers and may have predictive and prognostic value in the treatment of cancer. We sought to apply published CN analysis methods to a large pan-cancer data set and characterize ubiquitous CN signatures across tumor types, including potential utility for treatment selection., Methods: We analyzed the landscape of CN features in 260,333 pan-cancer samples. We examined the association of 10 signatures with genomic alterations and clinical characteristics and trained a machine learning classifier using CN and insertion and deletion features to detect homologous recombination deficiency signature (HRDsig) positivity. Clinical outcomes were assessed using a real-world clinicogenomic database (CGDB) of comprehensive genomic profiling linked to deidentified, electronic health record-derived clinical data., Results: CN signatures were prevalent across cancer types and associated with diverse processes including focal tandem duplications, seismic amplifications, genome-wide loss of heterozygosity (gLOH), and HRD. Our novel HRDsig outperformed gLOH in predicting BRCAness and effectively distinguished biallelic BRCA and homologous recombination-repair wild-type (HRRwt) samples pan-tumor, demonstrating high sensitivity to detect biallelic BRCA in ovarian (93%) and other HRD-associated cancers (80%-87%). Pan-tumor prevalence of HRDsig was 6.4%. HRRwt cases represented a significant fraction of the HRDsig-positive cohort, likely reflecting a population with nongenomic mechanisms of HRD. In ovarian and prostate CGDBs, HRDsig identified more patients than gLOH and had predictive value for poly (ADP-ribose) polymerase inhibitor (PARPi) benefit., Conclusion: Tumor CN profiles are informative, revealing diverse processes active in cancer. We describe the landscape of 10 CN signatures in a large pan-cancer cohort, including two associated with HRD. We trained a machine learning-based HRDsig that robustly identified BRCAness and associated with biallelic BRCA pan-tumor, and was predictive of PARPi benefit in real-world ovarian and prostate data sets.
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- 2023
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36. Integrative Analysis of a Large Real-World Cohort of Small Cell Lung Cancer Identifies Distinct Genetic Subtypes and Insights into Histologic Transformation.
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Sivakumar S, Moore JA, Montesion M, Sharaf R, Lin DI, Colón CI, Fleishmann Z, Ebot EM, Newberg JY, Mills JM, Hegde PS, Pan Q, Dowlati A, Frampton GM, Sage J, and Lovly CM
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- Humans, Mutation, Small Cell Lung Carcinoma pathology, Lung Neoplasms pathology, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Neuroendocrine genetics
- Abstract
Small cell lung cancer (SCLC) is a recalcitrant neuroendocrine carcinoma with dismal survival outcomes. A major barrier in the field has been the relative paucity of human tumors studied. Here we provide an integrated analysis of 3,600 "real-world" SCLC cases. This large cohort allowed us to identify new recurrent alterations and genetic subtypes, including STK11-mutant tumors (1.7%) and TP53/RB1 wild-type tumors (5.5%), as well as rare cases that were human papillomavirus-positive. In our cohort, gene amplifications on 4q12 are associated with increased overall survival, whereas CCNE1 amplification is associated with decreased overall survival. We also identify more frequent alterations in the PTEN pathway in brain metastases. Finally, profiling cases of SCLC containing oncogenic drivers typically associated with NSCLC demonstrates that SCLC transformation may occur across multiple distinct molecular cohorts of NSCLC. These novel and unsuspected genetic features of SCLC may help personalize treatment approaches for this fatal form of cancer., Significance: Minimal changes in therapy and survival outcomes have occurred in SCLC for the past four decades. The identification of new genetic subtypes and novel recurrent mutations as well as an improved understanding of the mechanisms of transformation to SCLC from NSCLC may guide the development of personalized therapies for subsets of patients with SCLC. This article is highlighted in the In This Issue feature, p. 1501., (©2023 The Authors; Published by the American Association for Cancer Research.)
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- 2023
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37. The 5-Factor Modified Frailty Index Score Predicts Return to the Operating Room for Patients Undergoing Posterior Spinal Fusion for Traumatic Spine Injury.
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Mehkri Y, Chakravarti S, Sharaf R, Reddy A, Fakhry J, Kuo CC, Hernandez J, Panther E, Tishad A, Gendreau J, Brown N, and Rahmathulla G
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- Humans, Retrospective Studies, Operating Rooms, Risk Factors, Postoperative Complications diagnosis, Frailty, Spinal Fusion
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Objective: Within the trauma spine surgery literature, the effect of patient frailty on postoperative outcomes for posterior spinal fusion (PSF) remains clear. In this study, the authors quantified the influence of the 5-factor modified frailty index (mFI-5) score on hospital length of stay, diagnosis of a postoperative infection, 30-day readmission, and 90-day return to operating room (OR)., Methods: The authors retrospectively reviewed the records of all patients with traumatic spine injury undergoing PSF by a single surgeon at our institution from 2016 to 2021. Data were extracted using manual chart review and the mFI-5 score was calculated using data on comorbidities. Bivariate (Mann-Whitney U test and Fisher exact test) and multivariate regressions (linear and logistic) revealed whether there was an independent relationship between patient frailty and postoperative outcomes., Results: The patient cohort included 263 patients (52.00 ± 19.04), 67 (25.5) were classified as frail, defined as having an mFI-5 score ≥2. Patients who were classified as frail were significantly more likely to have diabetes (odds ratio = 21.53; P < 0.001) and active cancer (odds ratio = 10.03; P = 0.004). Patients with mFI-5 scores ≥2 were also significantly older (P < 0.001) and had higher body mass index (BMI) (P = 0.007). Patients with mFI-5 scores >2 were more likely to return to the OR (odds ratio = 2.43; P = 0.037) on bivariate analysis. When controlling for demographics and clinical characteristics, mFI-5 score independently predicted return to OR (odds ratio = 1.294; P = 0.041)., Conclusions: Patient frailty independently predicted a return to OR in patients undergoing PSF for traumatic spine injury. Future studies can investigate methods for patient risk optimization to reduce morbidity and mortality., (Published by Elsevier Inc.)
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- 2023
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38. Autologous neutralizing antibodies increase with early antiretroviral therapy and shape HIV rebound after treatment interruption.
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Esmaeilzadeh E, Etemad B, Lavine CL, Garneau L, Li Y, Regan J, Wong C, Sharaf R, Connick E, Volberding P, Sagar M, Seaman MS, and Li JZ
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- Humans, Anti-Retroviral Agents therapeutic use, Proviruses, Immunoglobulin G, HIV Antibodies, Viral Load, Antibodies, Neutralizing therapeutic use, HIV Infections
- Abstract
Early initiation of antiretroviral therapy (ART) alters viral rebound kinetics after analytic treatment interruption (ATI) and may play a role in promoting HIV-1 remission. Autologous neutralizing antibodies (aNAbs) represent a key adaptive immune response in people living with HIV-1. We aimed to investigate the role of aNAbs in shaping post-ATI HIV-1 rebound variants. We performed single-genome amplification of HIV-1 env from pre-ART and post-ATI plasma samples of 12 individuals who initiated ART early after infection. aNAb activity was quantified using pseudoviruses derived from the most common plasma variant, and the serum dilution that inhibited 50% of viral infections was determined. aNAb responses matured while participants were on suppressive ART, because on-ART plasma and purified immunoglobulin G (IgG) demonstrated improved neutralizing activity against pre-ART HIV-1 strains when compared with pre-ART plasma or purified IgG. Post-ATI aNAb responses exerted selective pressure on the rebounding viruses, because the post-ATI HIV-1 strains were more resistant to post-ATI plasma neutralization compared with the pre-ART virus. Several pre-ATI features distinguished post-treatment controllers from noncontrollers, including an infecting HIV-1 sequence that was more similar to consensus HIV-1 subtype B, more restricted proviral diversity, and a stronger aNAb response. Post-treatment control was also associated with the evolution of distinct N-glycosylation profiles in the HIV-1 envelope. In summary, aNAb responses appeared to mature after early initiation of ART and applied selective pressure on rebounding viruses. The combination of aNAb activity with select HIV-1 sequence and reservoir features identified individuals with a greater chance of post-treatment control.
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- 2023
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39. Deep brain stimulation, lesioning, focused ultrasound: update on utility.
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Reddy A, Hosseini MR, Patel A, Sharaf R, Reddy V, Tabarestani A, and Lucke-Wold B
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Procedures for neurological disorders such as Parkinsons Disease (PD), Essential Tremor (ET), Obsessive Compulsive Disorder (OCD), Tourette's Syndrome (TS), and Major Depressive Disorder (MDD) tend to overlap. Common therapeutic procedures include deep brain stimulation (DBS), lesioning, and focused ultrasound (FUS). There has been significant change and innovation regarding targeting mechanisms and new advancements in this field allowing for better clinical outcomes in patients with severe cases of these conditions. In this review, we discuss advancements and recent discoveries regarding these three procedures and how they have led to changes in utilization in certain conditions. We further discuss the advantages and drawbacks of these treatments in certain conditions and the emerging advancements in brain-computer interface (BCI) and its utility as a therapeutic for neurological disorders., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2023 the Author(s), licensee AIMS Press.)
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- 2023
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40. Letter: Planning Brain Tumor Resection Using a Probabilistic Atlas of Cortical and Subcortical Structures Critical for Functional Processing: A Proof of Concept.
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Shalom M, Mehkri Y, Sharaf R, Reilly T, and Gendreau J
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- Humans, Stereotaxic Techniques, Brain surgery, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Brain Neoplasms pathology
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- 2023
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41. Cost Savings Associated with Vacuum-Assisted Closure in Trauma Patients Undergoing Posterior Spinal Fusion.
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Mehkri Y, Sharaf R, Tishad A, Gendreau J, Hernandez J, Panther E, Pafford R, and Rahmathulla G
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- Humans, Surgical Wound Infection epidemiology, Cost Savings, Treatment Outcome, Retrospective Studies, Negative-Pressure Wound Therapy methods, Spinal Fusion adverse effects
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Objective: To investigate the implications of vacuum-assisted closure (VAC) versus standard wound dressings on postoperative posterior spinal fusion (PSF) wounds with respect to potential cost savings associated with reduced incidence of surgical site infections., Methods: This was a retrospective review of trauma patients who underwent open PSF under the care of a single surgeon at a Level I trauma center. Patients were postoperatively monitored for 90 days. Statistical analysis was performed with χ
2 testing with the calculation of number needed to treat values., Results: Inclusion criteria were met by 208 patients who underwent open PSF. The χ2 test revealed a significant increase in incidence of surgical site infections (20% vs. 8%; P = 0.021) in the non-VAC group (n = 112) compared with the VAC group (n = 96). Cost-benefit analysis revealed that use of VAC in patients undergoing open PSF could enable a mean cost savings of $163,492 per 100 patients., Conclusions: Use of VAC in patients undergoing open PSF was associated with a 2-fold decrease in incidence of surgical site infections and an infection-related cost savings of $163,492 per 100 patients. Further investigation is needed to ascertain additional benefits of VAC usage in patients undergoing open PSF., (Copyright © 2022. Published by Elsevier Inc.)- Published
- 2023
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42. Letter to the editor regarding "The majority of ruptured aneurysms are small with low rupture risk scores".
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Mehkri Y, Reilly T, Sharaf R, and Shalom M
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- Humans, Risk Factors, Retrospective Studies, Aneurysm, Ruptured, Intracranial Aneurysm complications, Intracranial Aneurysm surgery
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Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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- 2023
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43. Prevalence of Congenital Heart Defects in Individuals With Down Syndrome in Saudi Arabia: A Systematic Review and Meta-Analysis.
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Sharaf R, Garout W, and Sharaf R
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Patients with Down syndrome (DS) are commonly diagnosed with congenital heart disease (CHD), which is the leading cause of mortality in this group during the first two years of life. This systematic review and meta-analysis aims to review the current publications to assess the pooled prevalence of overall CHDs in individuals with DS in KSA. We conducted the search on the databases PubMed, EBSCO, Scopus, Web of Science through Clarivate, and Google Scholar using Boolean operators and various keywords. The Rayyan - Intelligent Systematic Reviews website (https://www.rayyan.ai/) was used for citation management and MedCalc® Statistical Software version 20.115 was used for the quantitative data synthesis (MedCalc Software Ltd., 2022, Ostend Belgium). We initially retrieved a total of 402 citations from the primary search and 10 articles were finally included after title screening and full-text assessment. A total of 1590 subjects were enrolled in the pooled analyses. The pooled prevalence of CHDs was found to be 66.1% (95% CI: 57.2% to 74.5%). There was significant heterogeneity (I2 = 92.2%), and inspection of the funnel plot shows the symmetrical distribution of plotted data. According to our study, 66% of DS patients in Saudi Arabia had one or more congenital cardiac defects. Due to the significant inter-study heterogeneity, the reliability of our results is, nevertheless, limited. We advise conducting more research to provide better data for determining the prevalence of CHD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sharaf et al.)
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- 2022
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44. Pituitary Apoplexy (PA): Delayed Diagnosis of a Rare Clinical Syndrome in a Patient With a Known Pituitary Adenoma.
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Mehkri Y, Leone E, Sharaf R, Hernandez J, Figueredo Rivas L, Tuna IS, and Shuhaiber H
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Pituitary apoplexy (PA) is a rare clinical syndrome in which the pituitary gland undergoes infarction or hemorrhage, predominantly in the setting of an underlying tumor. We report on apoplexy of an expanding pituitary macroadenoma that was compressing the optic chiasm in a patient with progressively worsening neurologic deficits. Due to the patient's rapidly declining clinical status and family's goals of care, no neurosurgical intervention took place, and the patient expired a few days following discharge to hospice. This case highlights the importance of early suspicion for apoplexy in a patient with a history of pituitary adenoma and signs of neurologic deficit., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Mehkri et al.)
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- 2022
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45. Letter to the Editor. Stratifying by publication type in Charting Outcomes in the Match reports.
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Mehkri Y, Sharaf R, Liu S, Shalom M, and Gendreau J
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- 2022
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46. Mutations in the TERC template sequence can be incorporated into the telomeres of human tumors.
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Sharaf R, Frampton GM, and Albacker LA
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- Humans, Mutation, RNA genetics, RNA metabolism, Telomere genetics, Telomere metabolism, Neoplasms genetics, Telomerase genetics, Telomerase metabolism
- Abstract
Telomerase-mediated lengthening is a mechanism by which some cancer cells avoid senescence-mediated cell cycle arrest due to shortened telomeres. By reverse transcribing an RNA template, encoded by TERC, the enzyme telomerase synthesizes the elongation of telomeric DNA using the 3' end of the chromosome as a primer. TERC harbors a highly conserved template region consisting of 11 nucleotides spanning hg19 coordinates chr3:169482793-169482803. In human cell lines, when TERC was mutated to alter its template region, telomerase generated the predicted mutant telomeric repeats. However, it is unknown if this can occur in human clinical samples. Here, we report on the rare occurrence of two tumor samples where TERC template mutations were reflected in telomeric repeats., Competing Interests: RS, GMF, and LAA are employees of Foundation Medicine, Inc., a wholly owned subsidiary of Roche Holdings, Inc. and Roche Finance Ltd, and these employees have equity interest in an affiliate of these Roche entities.
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- 2022
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47. A pan-cancer landscape of telomeric content shows that RAD21 and HGF alterations are associated with longer telomeres.
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Sharaf R, Montesion M, Hopkins JF, Song J, Frampton GM, and Albacker LA
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- Cell Cycle Proteins genetics, DNA-Binding Proteins genetics, Hepatocyte Growth Factor genetics, Hepatocyte Growth Factor metabolism, Humans, Telomere genetics, Telomere Homeostasis, X-linked Nuclear Protein genetics, Neoplasms genetics, Telomerase genetics
- Abstract
Background: Cancer cells can proliferate indefinitely through telomere maintenance mechanisms. These mechanisms include telomerase-dependent elongation, mediated by TERT activation, and alternative lengthening of telomeres (ALT), linked to loss of ATRX or DAXX., Methods: We analyzed the telomeric content of 89,959 tumor samples within the Foundation Medicine dataset and investigated the genomic determinants of high telomeric content, linking them to clinical outcomes, when available., Results: Telomeric content varied widely by disease type with leiomyosarcoma having the highest and Merkel cell carcinoma having the lowest telomeric content. In agreement with previous studies, telomeric content was significantly higher in samples with alterations in TERC, ATRX, and DAXX. We further identified that amplifications in two genes, RAD21 and HGF, were enriched in samples with high telomeric content, which was confirmed using the PCAWG/ICGC dataset. We identified the minimal amplified region associated with high telomeric content for RAD21 (8q23.1-8q24.12), which excludes MYC, and for HGF (7q21.11). Our results demonstrated that RAD21 and HGF exerted an additive telomere lengthening effect on samples with existing alterations in canonical genes previously associated with telomere elongation. Furthermore, patients with breast cancer who harbor RAD21 alterations had poor median overall survival and trended towards higher levels of Ki-67 staining., Conclusions: This study highlights the importance of the role played by RAD21 (8q23.1-8q24.12) and HGF (7q21.11) in the lengthening of telomeres, supporting unlimited replication in tumors. These findings open avenues for work aimed at targeting this crucial pathway in tumorigenesis., (© 2022. The Author(s).)
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- 2022
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48. Room for improvement in capturing cancer family history in a gynecologic oncology outpatient setting.
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Lin J, Wolfe I, Ahsan MD, Krinsky H, Lackner AI, Pelt J, Bolouvi K, Gamble C, Thomas C, Christos PJ, Cantillo E, Holcomb K, Chapman-Davis E, Sharaf R, Lipkin SM, Blank SV, and Frey MK
- Abstract
The literature demonstrates that the quality of cancer family history (CFH) as currently collected in the outpatient setting is inadequate to assess disease risk. Prior to implementation of a web-based application for cancer family history collection, we aimed to review the quality of collected CFH in a gynecologic oncology outpatient clinic and determine contributing patient factors. Medical records were reviewed for 200 new patients presenting between 4/2019-7/2019. CFH was collected during the patient interview and evaluated for inclusion of eight elements based on standards set by the genetics community. Univariate and multivariable linear regression analyses were utilized to evaluate the effect of patient characteristics on the number of relatives included in the CFH. Among our cohort of 200 patients, CFH was documented for 185 patients (92.5%). On univariate analysis, patients with a family history of cancer and prior genetic testing had significantly greater median number of relatives included in the CFH. On multivariable analysis, patients with family members with cancer had significantly more relatives included. Our data are consistent with the literature, suggesting that the current collection methods may not adequately capture all measures of a high quality CFH. Patients reporting no family history of cancer and those without prior genetic testing were least likely to have CFH that included key quality elements and these patients might benefit from health information technology CFH collection tools., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Inc.)
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- 2022
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49. Frequency of post treatment control varies by antiretroviral therapy restart and viral load criteria.
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Fajnzylber J, Sharaf R, Hutchinson JN, Aga E, Bosch RJ, Hartogensis W, Jacobson JM, Connick E, Volberding P, Skiest DJ, Margolis D, Sneller MC, Little SJ, Gulick RM, Mellors JW, Gandhi RT, Schooley RT, Henry K, Tebas P, Deeks S, Chun TW, Collier AC, Hecht FM, and Li JZ
- Subjects
- Humans, Serologic Tests, Viral Load, HIV Infections drug therapy
- Abstract
Clinical trials including an analytical treatment interruption (ATI) are vital for evaluating the efficacy of novel strategies for HIV remissions. We briefly describe an interactive tool for predicting viral rebound timing in ATI trials and the impact of posttreatment controller (PTC) definitions on PTC frequency estimates. A 4-week viral load threshold of 1000 cps/ml provides both high specificity and sensitivity for PTC detection. PTC frequency varies greatly based on the definition of a PTC., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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50. Genomic Profiling of Combined Hepatocellular Cholangiocarcinoma Reveals Genomics Similar to Either Hepatocellular Carcinoma or Cholangiocarcinoma.
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Murugesan K, Sharaf R, Montesion M, Moore JA, Pao J, Pavlick DC, Frampton GM, Upadhyay VA, Alexander BM, Miller VA, Javle MM, Bekaii Saab TS, Albacker LA, Ross JS, and Ali SM
- Subjects
- Adult, Aged, Aged, 80 and over, Bile Duct Neoplasms pathology, Carcinoma, Hepatocellular pathology, Cholangiocarcinoma pathology, Female, Genomics, Humans, Liver pathology, Liver Neoplasms pathology, Machine Learning, Male, Middle Aged, Young Adult, Bile Duct Neoplasms genetics, Carcinoma, Hepatocellular genetics, Cholangiocarcinoma genetics, Liver Neoplasms genetics
- Abstract
Purpose: Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare, aggressive primary liver carcinoma, with morphologic features of both hepatocellular carcinomas (HCC) and liver cholangiocarcinomas (CCA)., Methods: The genomic profiles of 4,975 CCA, 1,470 HCC, and 73 cHCC-CCA cases arising from comprehensive genomic profiling in the course of clinical care were reviewed for genomic alterations (GA), tumor mutational burden, microsatellite instability status, genomic loss of heterozygosity, chromosomal aneuploidy, genomic ancestry, and hepatitis B virus status., Results: In cHCC-CCA, GA were most common in TP53 (65.8%), TERT (49.3%), and PTEN (9.6%), and 24.6% cHCC-CCA harbored potentially targetable GA. Other GA were predominantly associated with either HCC or CCA, including, but not limited to, TERT , FGFR2 , IDH1 , and presence of hepatitis B virus. On the basis of these features, a machine learning (ML) model was trained to classify a cHCC-CCA case as CCA-like or HCC-like. Of cHCC-CCA cases, 16% (12/73) were ML-classified as CCA-like and 58% (42/73) cHCC-CCA were ML-classified as HCC-like. The ML model classified more than 70% of cHCC-CCA as CCA-like or HCC-like on the basis of genomic profiles, without additional clinico-pathologic input., Conclusion: These findings demonstrate the use of ML for classification as based on a targeted exome panel used during routine clinical care. Classification of cHCC-CCA by genomic features alone creates insights into the biology of the disease and warrants further investigation for relevance to clinical care., Competing Interests: Karthikeyan Murugesan Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Pharma AG Patents, Royalties, Other Intellectual Property: Antibiotic resistance causation identification (US10629291B2) filed with Koninklijke Philips NV, Analytic prediction of antibiotic susceptibility (US20190279738A1) filed with Koninklijke Philips NV, Methods and devices for characterizing and treating combined hepatocellular cholangiocarcinoma, with Foundation Medicine Inc Travel, Accommodations, Expenses: Foundation Medicine Radwa Sharaf Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Meagan Montesion Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Jay A. Moore Employment: Foundation Medicine Stock and Other Ownership Interests: Roche James Pao Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Research Funding: Foundation Medicine Patents, Royalties, Other Intellectual Property: Provisional patent submitted for Foundation Medicine, dealing with machine learning for gene predictions Dean C. Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Garrett M. Frampton Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Vivek A. Upadhyay Employment: EQRx Stock and Other Ownership Interests: EQRx Consulting or Advisory Role: Foundation Medicine Brian M. Alexander Employment: Foundation Medicine Leadership: Foundation Medicine Stock and Other Ownership Interests: Roche Research Funding: Lilly, Puma Biotechnology, Celgene Open Payments Link: https://openpaymentsdata.cms.gov/physician/854258/summary Vincent A. Miller Employment: Foundation Medicine, EQRx Leadership: Revolution Medicines Stock and Other Ownership Interests: Foundation Medicine, Mirati Therapeutics, Revolution Medicines, EQRx Patents, Royalties, Other Intellectual Property: Receives periodic royalties related to T790M patent awarded to Memorial Sloan Kettering Cancer Center Milind M. Javle Consulting or Advisory Role: QED Therapeutics, Oncosil, Incyte, Mundipharma EDO GmbH, AstraZeneca, Merck, EMD Serono Other Relationship: Rafael Pharmaceuticals, Incyte, Pieris Pharmaceuticals, Merck, Merck Serono, Novartis, Seattle Genetics, BeiGene, QED Therapeutics, Bayer Tanios S. Bekaii Saab Consulting or Advisory Role: Amgen, Ipsen, Lilly, Bayer, Roche/Genentech, AbbVie, Incyte, Immuneering, Seattle Genetics, Pfizer, Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation Medicine Patents, Royalties, Other Intellectual Property: Patent WO/2018/183488, Patent WO/2019/055687 Other Relationship: Exelixis, Merck, AstraZeneca, Lilly, Pancreatic Cancer Action Network Lee A. Albacker Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Jeffrey S. Ross Employment: Foundation Medicine Leadership: Foundation Medicine Stock and Other Ownership Interests: Foundation Medicine Consulting or Advisory Role: Celsius Therapeutics, Tango Therapeutics Research Funding: Foundation Medicine Siraj M. Ali Employment: EQRx Consulting or Advisory Role: Elevation Oncology, In8bio, Pillar Biosciences, Takeda, ArcherDx Stock and Other Ownership Interests: In8bio, Pillar Biosciences, EQRx Patents: Foundation Medicine No other potential conflicts of interest were reported. Karthikeyan Murugesan Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Pharma AG Patents, Royalties, Other Intellectual Property: Antibiotic resistance causation identification (US10629291B2) filed with Koninklijke Philips NV, Analytic prediction of antibiotic susceptibility (US20190279738A1) filed with Koninklijke Philips NV, Methods and devices for characterizing and treating combined hepatocellular cholangiocarcinoma, with Foundation Medicine Inc Travel, Accommodations, Expenses: Foundation Medicine Radwa Sharaf Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Meagan Montesion Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Jay A. Moore Employment: Foundation Medicine Stock and Other Ownership Interests: Roche James Pao Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Research Funding: Foundation Medicine Patents, Royalties, Other Intellectual Property: Provisional patent submitted for Foundation Medicine, dealing with machine learning for gene predictions Dean C. Pavlick Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Garrett M. Frampton Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Vivek A. Upadhyay Employment: EQRx Stock and Other Ownership Interests: EQRx Consulting or Advisory Role: Foundation Medicine Brian M. Alexander Employment: Foundation Medicine Leadership: Foundation Medicine Stock and Other Ownership Interests: Roche Research Funding: Lilly, Puma Biotechnology, Celgene Open Payments Link: https://openpaymentsdata.cms.gov/physician/854258/summary Vincent A. Miller Employment: Foundation Medicine, EQRx Leadership: Revolution Medicines Stock and Other Ownership Interests: Foundation Medicine, Mirati Therapeutics, Revolution Medicines, EQRx Patents, Royalties, Other Intellectual Property: Receives periodic royalties related to T790M patent awarded to Memorial Sloan Kettering Cancer Center Milind M. Javle Consulting or Advisory Role: QED Therapeutics, Oncosil, Incyte, Mundipharma EDO GmbH, AstraZeneca, Merck, EMD Serono Other Relationship: Rafael Pharmaceuticals, Incyte, Pieris Pharmaceuticals, Merck, Merck Serono, Novartis, Seattle Genetics, BeiGene, QED Therapeutics, Bayer Tanios S. Bekaii Saab Consulting or Advisory Role: Amgen, Ipsen, Lilly, Bayer, Roche/Genentech, AbbVie, Incyte, Immuneering, Seattle Genetics, Pfizer, Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation Medicine Patents, Royalties, Other Intellectual Property: Patent WO/2018/183488, Patent WO/2019/055687 Other Relationship: Exelixis, Merck, AstraZeneca, Lilly, Pancreatic Cancer Action Network Lee A. Albacker Employment: Foundation Medicine Stock and Other Ownership Interests: Roche Jeffrey S. Ross Employment: Foundation Medicine Leadership: Foundation Medicine Stock and Other Ownership Interests: Foundation Medicine Consulting or Advisory Role: Celsius Therapeutics, Tango Therapeutics Research Funding: Foundation Medicine Siraj M. Ali Employment: EQRx Consulting or Advisory Role: Elevation Oncology, In8bio, Pillar Biosciences, Takeda, ArcherDx Stock and Other Ownership Interests: In8bio, Pillar Biosciences, EQRx Patents: Foundation Medicine No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)
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- 2021
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