36 results on '"Justin Jiang"'
Search Results
2. 3130 Evaluation of the delivery of specialist first seizure care in Australia
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David Vaughan, Emma Foster, Patrick Carney, Wendyl D'Souza, and Justin Jiang
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Published
- 2024
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3. Improvement in survival of acute myeloid leukemia and myelodysplastic syndrome patients following allogeneic transplant: a long-term institutional experience
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Audrey M. Sigmund, Justin Jiang, Qiuhong Zhao, Patrick Elder, Don M. Benson, Sumithira Vasu, Samantha Jaglowski, Alice S. Mims, Hannah Choe, Karilyn Larkin, Jonathan E. Brammer, Sarah A. Wall, Nicole Grieselhuber, William Basem, Sam Penza, Yvonne A. Efebera, and Nidhi Sharma
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acute myeloid leukemia ,allogenic transplantation ,overall survival ,progression-free survival ,graft-versus-host disease ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundAllogeneic stem cell transplant (allo-SCT) plays a key role in the treatment of patients with both acute myeloid leukemia (AML) and myelodysplastic (MDS). Outcomes of allo-SCT have improved with optimization of transplant practices. We sought to evaluate trends in survival in AML and MDS patients undergoing allo-SCT at our institution from 1984 to 2018.MethodsA retrospective analysis of 900 consecutive AML and MDS patients undergoing allo-SCT was performed. Patients were divided by year of transplant for analysis. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints included non-relapse mortality (NRM), graft-versus-host disease (GVHD), GVHD-free relapse free survival (GRFS), and transplant complications.ResultsWe found a significant improvement in survival from 1984 to 2018 with 5-year PFS and OS improving from 17% to 49% and 17% to 53%, respectively (statistically significant difference since 2004; p
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- 2023
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4. Impact of Race and Geographic Area of Residence on Outcomes After Allogeneic Stem Cell Transplant
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Audrey M. Sigmund, Qiuhong Zhao, Justin Jiang, Patrick Elder, Don M. Benson, Ashley Rosko, Naresh Bumma, Abdullah Khan, Srinivas Devarakonda, Sumithira Vasu, Samantha Jaglowski, Alice Mims, Hannah Choe, Karilyn Larkin, Jonathan Brammer, Sarah Wall, Nicole Grieselhuber, Ayman Saad, Sam Penza, Yvonne A. Efebera, and Nidhi Sharma
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race ,geographic location of residence ,allogeneic transplant ,health disparities ,GvHD ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
BackgroundAllogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of hematologic disorders. However, it requires highly specialized care that is only available at select centers across the country. Thus, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Our study aimed to assess the impact of race and location of residence on outcomes of allo-HCT.MethodsWe performed a retrospective analysis of all patients who underwent allo-HCT at the Ohio State University from 1984 to 2018. Patients were divided by race (Caucasian, African American, and other) and grouped by zip code into rural, suburban, and urban groups. Primary endpoints included progression-free survival (PFS) and overall survival (OS).ResultsOf the 1,943 patients included in the study, 94.3% self-identified as Caucasian, 4.6% African American, and 1.1% other. In total, 63.4% lived in rural areas, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS by race (p = 0.15, 0.21) or place of residence (p = 0.39, 0.17). In addition, no difference in nonrelapse mortality, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) was seen among the race or place of residence.ConclusionOur study suggests that when appropriate access to HCT is given, there is no difference in outcomes based on race, ethnicity or place of primary residence. Further research is needed to further evaluate barriers for these patients to undergo transplant and help mitigate these barriers.
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- 2022
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5. Bayesian Network Learning for Classification via Transfer Method.
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April Hua Liu, Zihao Cheng, and Justin Jiang
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- 2019
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6. eMPRess: a systematic cophylogeny reconciliation tool.
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Santi Santichaivekin, Qing Yang, Jingyi Liu, Ross Mawhorter, Justin Jiang, Trenton Wesley, Yi-Chieh Wu, and Ran Libeskind-Hadas
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- 2021
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7. Research About Apple’s Marketing Strategy and Consumer Behavior
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Weihong Justin Jiang, Ruizhe Li, and Wufei Shao
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This paper mainly tells how Apple is successful, including how to attract new customers, how to retain old customers, and so on. The reason for choosing this topic for research is to analyze Apple's success and its perfect marketing strategy with the marketing analysis method of Jonah Burger. This paper will use a Questionnaire, Modal analyses, and Data collection to obtain evidence. In the Result section, this paper will use three factors from Jonah Burger's STEPPS: Social Currency, Practical value, and Emotion, to describe Apple's success. Meanwhile, professional market analysis frameworks such as SWOT analysis and Further suggestions and Strategies will be used in the Discussion to analyze the current situation and future of apple’s market. This article will give readers a better understanding of Apple's success and can be used as a reference.
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- 2022
8. Control Strategy for Improved After-Etch Overlay at Wafer Edge of DRAM Layers in High-Volume Manufacturing
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Junjun Zhang, Jimmy Chang, Charlie Huang, Wei Zhang, Helei Sun, Xiaofang Zhou, Bing Wang, Fan Huang, Hao Jing, Justin Jiang, Matthijs van Reeuwijk, Maja Vidojkovic, and Hua Li
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- 2022
9. Fast In-Device Overlay Metrology on DRAM Storage Node Contact and Its Applications in Process Control
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Rui Qin, Shaowen Qiu, Yunsheng Xia, Silva Hu, Jimmy Chang, Junjun Zhang, Wei Zhang, Panpan Wang, Xiaofang Zhou, Elton Bitincka, Giacomo Miceli, Sylvia Yuan, Natalia Drabik, Pavel Izikson, Giulia Argento, Yvon Chai, Yu Liu, Justin Jiang, Hao Jing, and Shaun Dai
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- 2021
10. Scribe Line Self Reference Targets to enable Accurate and Robust After-Etch Overlay Metrology of Active layer
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Jimmy Chang, Junjun Zhang, Wei Zhang, Panpan Wang, Xiaofang Zhou, Rui Qin, Silva Hu, Shaowen Qiu, Yunsheng Xia, Giacomo Miceli, Sylvia Yuan, Natalia Drabik, Pavel Izikson, Giulia Argento, Bas van der Broek, Elton Bitincka, Hao Jing, Shaun Dai, Yvon Chai, Yu Liu, and Justin Jiang
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- 2021
11. Longitudinal Survival Outcomes in Allogeneic Stem Cell Transplantation: An Institutional Experience
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Justin Jiang, Audrey M. Sigmund, Qiuhong Zhao, Patrick Elder, Don M. Benson, Sumithira Vasu, Samantha Jaglowski, Alice Mims, Hannah Choe, Karilyn Larkin, Jonathan E. Brammer, Sarah Wall, Nicole Grieselhuber, Ayman Saad, Sam Penza, Yvonne A. Efebera, and Nidhi Sharma
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Cancer Research ,allogenic transplantation ,overall survival ,progression-free survival ,graft-versus-host disease ,Oncology - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many hematological disorders, but is often complicated by relapse of the underlying disease, graft-versus-host disease (GVHD), and infectious complications. We conducted a retrospective analysis on patients undergoing allo-SCT from 1984 to 2018 to better understand how survival has changed longitudinally with therapeutic advancements made to mitigate these complications. Method: We analyzed data from 1943 consecutive patients who received allo-SCT. Patients were divided into groups (gps) based on the year (yr) of transplant. Primary endpoints were overall survival (OS), progression free survival (PFS), and GVHD-free relapse-free survival (GRFS). Secondary endpoints were the cumulative incidences of grade II–IV and grade III–IV acute GVHD (aGVHD), chronic GVHD (cGVHD), and non-relapse mortality (NRM). Results: Our study found statistically significant improvements in OS, PFS, and GRFS. Five-year PFS among the groups increased from 24% to 48% over the years. Five-year OS increased from 25% to 53%. Five-year GRFS significantly increased from 6% to 14%, but remained relatively unchanged from 2004 to 2018. Cumulative incidences of grade II–IV aGVHD increased since 2009 (p < 0.001). However, cumulative incidence of NRM decreased since 2004 (p < 0.001). Conclusions: Our data show improved OS, PFS, and GRFS post allo-SCT over decades. This may be attributed to advances in supportive care and treatments focused on mitigation of GVHD and relapse.
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- 2022
12. Impact of Race and Geographic Area of Residence on Outcomes After Allogeneic Stem Cell Transplant
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Audrey M. Sigmund, Qiuhong Zhao, Justin Jiang, Patrick Elder, Don M. Benson, Ashley Rosko, Naresh Bumma, Abdullah Khan, Srinivas Devarakonda, Sumithira Vasu, Samantha Jaglowski, Alice Mims, Hannah Choe, Karilyn Larkin, Jonathan Brammer, Sarah Wall, Nicole Grieselhuber, Ayman Saad, Sam Penza, Yvonne A. Efebera, and Nidhi Sharma
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Cancer Research ,Oncology - Abstract
BackgroundAllogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of hematologic disorders. However, it requires highly specialized care that is only available at select centers across the country. Thus, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Our study aimed to assess the impact of race and location of residence on outcomes of allo-HCT.MethodsWe performed a retrospective analysis of all patients who underwent allo-HCT at the Ohio State University from 1984 to 2018. Patients were divided by race (Caucasian, African American, and other) and grouped by zip code into rural, suburban, and urban groups. Primary endpoints included progression-free survival (PFS) and overall survival (OS).ResultsOf the 1,943 patients included in the study, 94.3% self-identified as Caucasian, 4.6% African American, and 1.1% other. In total, 63.4% lived in rural areas, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS by race (p = 0.15, 0.21) or place of residence (p = 0.39, 0.17). In addition, no difference in nonrelapse mortality, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) was seen among the race or place of residence.ConclusionOur study suggests that when appropriate access to HCT is given, there is no difference in outcomes based on race, ethnicity or place of primary residence. Further research is needed to further evaluate barriers for these patients to undergo transplant and help mitigate these barriers.
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- 2021
13. Allogenic Transplantation in Older Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
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Audrey M. Sigmund, Justin Jiang, Qiuhong Zhao, Patrick Elder, Ashley Rosko, Naresh Bumma, Abdullah Khan, Srinivas Devarakonda, Sumithira Vasu, Samantha Jaglowski, Alice Mims, Hannah Choe, Karilyn Larkin, Jonathan E. Brammer, Sarah A. Wall, Nicole Grieselhuber, Ayman Saad, Sam Penza, Marcos De Lima, Don M Benson, Yvonne Efebera, and Nidhi Sharma
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2022
14. Outcomes of Bone Marrow Compared to Peripheral Blood for Haploidentical Transplantation
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Karilyn Larkin, Audrey M. Sigmund, Alice S. Mims, Patrick Elder, Nicole Grieselhuber, Ayman Saad, Yvonne A. Efebera, Qiuhong Zhao, Srinivas Devarakonda, Sarah A Wall, Ashley E. Rosko, Don M. Benson, Muhammad Salman Faisal, Justin Jiang, Sumithira Vasu, Hannah Choe, Nidhi Sharma, Naresh Bumma, Abdullah Khan, Jonathan E. Brammer, Sam Penza, Samantha Jaglowski, and Maria Chaudhry
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medicine.medical_specialty ,bone marrow ,Cyclophosphamide ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,haploidentical transplantation ,business.industry ,Incidence (epidemiology) ,allogenic transplantation ,General Medicine ,peripheral blood ,Confidence interval ,Peripheral blood ,Transplantation ,medicine.anatomical_structure ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Cohort ,Medicine ,Bone marrow ,Stem cell ,business ,030215 immunology ,medicine.drug - Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical (haplo) donor has emerged as a suitable alternative in the absence of a matched donor. However, haplo-HCT patients have a higher risk of graft-versus-host disease (GVHD). Hence, bone marrow (BM) stem cell source and post-transplant cyclophosphamide (PTCy) have been routinely used to help mitigate this. Due to ease of collection, peripheral blood (PB) stem cells are increasingly being considered for haplo-HCT. We retrospectively analyzed 74 patients (42 BM and 32 PB) who underwent haplo-HCT at Ohio State University from 2009 to 2018. Median age at transplant was 60 years (yrs) for BM and 54 yrs for PB, (p = 0.45). There was no difference in OS (p = 0.13) and NRM (p = 0.75) as well as PFS (p = 0.10) or GRFS (p = 0.90) between the groups. The BM cohort showed a 3-year OS rate of 63% (95% confidence interval (CI): 46–76), and 3-year PFS of 49% (95% CI: 33–63). For the PB group, 3-year OS and PFS were 78% (95% CI: 59–89) and 68% (95% CI: 49–82), respectively. There were no differences in the incidence of acute GVHD (grade II-IV) (p = 0.31) and chronic GVHD (p = 0.18). Patients receiving BM had a significantly higher risk for relapse with relapse rates by 2 years at 36% (95% CI: 22–50) vs. 16% (95% CI: 6–31) for PB (p = 0.03). The findings from this study suggest that PB is an excellent alternative to BM for haplo-HCT.
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- 2021
15. Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer
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Junan Li, Chengxiang Zhang, Xiao Luo, Wenqing Li, Binbin Deng, Justin Jiang, Xinfu Zhang, Bin Li, Weiyu Zhao, Yizhou Dong, Chunxi Zeng, and David W. McComb
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Combination therapy ,medicine.medical_treatment ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,chemistry.chemical_compound ,Breast cancer ,In vivo ,Medicine ,General Materials Science ,Electrical and Electronic Engineering ,Cytotoxicity ,Triple-negative breast cancer ,Chemotherapy ,business.industry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Paclitaxel ,chemistry ,Cancer research ,Personalized medicine ,0210 nano-technology ,business - Abstract
Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane(®) and Lipusu(®) used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.
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- 2019
16. Functionalized lipid-like nanoparticles for in vivo mRNA delivery and base editing
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Xinfu Zhang, Wenqing Li, Luis A. Barrera, Francine Gregoire, Chengxiang Zhang, Xucheng Hou, Weiyu Zhao, Denise E. Sabatino, Giang N. Nguyen, Binbin Deng, Robert Dorkin, Yizhou Dong, Manmohan Singh, Jingyue Yan, Delai Chen, David W. McComb, Justin Jiang, Shi Du, Chunxi Zeng, and Aalok Shah
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Gene Editing ,Messenger RNA ,Multidisciplinary ,Chemistry ,PCSK9 ,Materials Science ,Low dose ,SciAdv r-articles ,Life Sciences ,Lipids ,Cell biology ,Mice ,In vivo ,Animals ,Nanoparticles ,RNA, Messenger ,Guide RNA ,Proprotein Convertase 9 ,Research Articles ,Research Article - Abstract
Biodegradable nanomaterials effectively deliver long messenger RNAs in animal models., Messenger RNA (mRNA) therapeutics have been explored to treat various genetic disorders. Lipid-derived nanomaterials are currently one of the most promising biomaterials that mediate effective mRNA delivery. However, efficiency and safety of this nanomaterial-based mRNA delivery remains a challenge for clinical applications. Here, we constructed a series of lipid-like nanomaterials (LLNs), named functionalized TT derivatives (FTT), for mRNA-based therapeutic applications in vivo. After screenings on the materials, we identified FTT5 as a lead material for efficient delivery of long mRNAs, such as human factor VIII (hFVIII) mRNA (~4.5 kb) for expression of hFVIII protein in hemophilia A mice. Moreover, FTT5 LLNs demonstrated high percentage of base editing on PCSK9 in vivo at a low dose of base editor mRNA (~5.5 kb) and single guide RNA. Consequently, FTT nanomaterials merit further development for mRNA-based therapy.
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- 2020
17. eMPRess: a systematic cophylogeny reconciliation tool
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Ross Mawhorter, Jingyi Liu, Santi Santichaivekin, Qing Yang, Ran Libeskind-Hadas, Trenton Wesley, Justin Jiang, and Yi-Chieh Wu
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Statistics and Probability ,Supplementary data ,0303 health sciences ,Information retrieval ,Phylogenetic tree ,Computer science ,Event (computing) ,030302 biochemistry & molecular biology ,MEDLINE ,Biochemistry ,Computer Science Applications ,Evolution, Molecular ,03 medical and health sciences ,Computational Mathematics ,Computational Theory and Mathematics ,Molecular Biology ,Algorithms ,Phylogeny ,Software ,030304 developmental biology - Abstract
Summary We describe eMPRess, a software program for phylogenetic tree reconciliation under the duplication-transfer-loss model that systematically addresses the problems of choosing event costs and selecting representative solutions, enabling users to make more robust inferences. Availability and implementation eMPRess is freely available at http://www.cs.hmc.edu/empress. Supplementary information Supplementary data are available at Bioinformatics online.
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- 2020
18. Bayesian Network Learning for Classification via Transfer Method
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Zihao Cheng, Justin Jiang, and April Hua Liu
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Training set ,business.industry ,Computer science ,Bayesian network ,02 engineering and technology ,Machine learning ,computer.software_genre ,ComputingMethodologies_PATTERNRECOGNITION ,Robustness (computer science) ,020204 information systems ,0202 electrical engineering, electronic engineering, information engineering ,Labeled data ,020201 artificial intelligence & image processing ,Artificial intelligence ,business ,Transfer of learning ,computer ,Interpretability - Abstract
In classification problem, Bayesian networks play an important role because of its efficiency and interpretability. Bayesian networks learning methods require enough data to produce reliable results. Unfortunately, in practice, the training data are often either too few, expensive to label, or easy to be outdated. However, there may be sufficient labeled data that are available in a different but related domain. Learning reliable Bayesian networks from limited data is difficult; and transfer learning might be used to improve the robustness of learned networks by combining data from auxiliary and related labeled dataset. In this paper, we propose a novel transfer learning method for Bayesian networks for classification that considers both structure and parameter learning. Our solution is to first construct the initial Bayesian networks model for auxiliary labeled data, and then revise the model according to an Expectation-Maximization (EM) algorithm, structure and parameters are revised by turns, in order to make it applicable to the target unlabeled dataset. We mainly apply our method on a special type of Bayesian networks, namely tree-based Bayesian network. To validate our approach, we evaluated the method on a real and typical classification scenario - text classification problem. We compared our method with other transfer learning method as well as the traditional supervised and semi-supervised learning algorithms. The experimental results show that our algorithm is very effective and obtains a significant improvement when we transfer knowledge from related dataset.
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- 2019
19. Ratiometric fluorescent probes for capturing endogenous hypochlorous acid in the lungs of mice
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Chengxiang Zhang, Bin Li, Xinfu Zhang, Weiyu Zhao, Xucheng Hou, Yizhou Dong, Wenqing Li, and Justin Jiang
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Lung ,Hypochlorous acid ,Lipopolysaccharide ,Endogeny ,Inflammation ,02 engineering and technology ,General Chemistry ,respiratory system ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Fluorescence ,3. Good health ,0104 chemical sciences ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Sense (molecular biology) ,medicine ,medicine.symptom ,Cyanine ,0210 nano-technology - Abstract
Hypochlorous acid (HClO) is a promising diagnostic marker for inflammation and relevant diseases. Although many probes were previously developed for HClO imaging, the development of organ targeting probes is still lacking. Herein, we designed and synthesized a series of cyanine derivatives as ratiometric fluorescent probes to detect endogenous HClO in the lungs with inflammation. By installing diverse lipid chains and amino groups on cyanine, we identified that ClO1, with one n-octadecane chain and two 2-[[2-(dimethylamino)ethyl]methylamino]-ethyl groups, is a superior probe to target the lungs over other major organs in mice. ClO1 was able to sense both exogenous and endogenous HClO in A549 (human lung epithelial) cells through fluorescence ratiometric imaging. In a lipopolysaccharide (LPS)-induced lung inflammation mouse model, ClO1 effectively captured endogenous HClO in the lungs after intravenous administration. Overall, these cyanine-derived probes merit further development as organ targeting HClO sensors.
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- 2018
20. Effect of Age on Outcomes of Allogeneic Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome
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Nicole Grieselhuber, Marcos de Lima, Karilyn Larkin, Justin Jiang, Jonathan E. Brammer, Samantha Jaglowski, Audrey M. Sigmund, Qiuhong Zhao, Maria Chaudhry, Naresh Bumma, Abdullah Khan, Srinivas Devarakonda, Alice S. Mims, Nidhi Sharma, Sam Penza, Yvonne A. Efebera, Hannah Choe, Ashley E. Rosko, Sumithira Vasu, Patrick Elder, Sarah A Wall, Don M. Benson, and Ayman Saad
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Oncology ,medicine.medical_specialty ,Allogeneic transplantation ,business.industry ,Immunology ,Myeloid leukemia ,Cell Biology ,Hematology ,Biochemistry ,hemic and lymphatic diseases ,Internal medicine ,medicine ,In patient ,business - Abstract
Background: Allogeneic stem cell transplantation (allo-SCT) has become an increasingly important consolidation treatment option for patients with acute myeloid leukemia (AML) and as upfront therapy for patients with high-risk myelodysplastic syndrome (MDS). Although the median age at diagnosis for both diseases is above 65 years, studies evaluating allo-SCT as treatment option for patients aged 65 years or older are limited. Further, as the population ages, the number of patients above 65 years considered for allo-SCT will continue to rise. Thus, the aim of our current investigation was to analyze outcomes based on age in AML/MDS patients Methods: A retrospective analysis was performed for all AML/MDS patients who received allo-SCT between January 1984 and December 2018 at our institution. Primary endpoints included progression free survival (PFS) and overall survival (OS). PFS was counted from the day of transplantation to relapse or death. OS was defined as survival from the day of allo-SCT until death from any cause, with censoring of patients known to be alive at the time of last follow-up. PFS and OS were calculated using Kaplan Meier Curves. Secondary endpoints included cumulative incidences of grade II-IV and III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, and non-relapse mortality (NRM). Cumulative incidence rates of aGVHD, cGVHD, relapse, NRM were estimated and compared using Gray's test accounting for competing risks. Results: The cohort consisted of 900 AML/MDS patients, with 150 patients ≥65 years and 750 patients The median time from diagnosis to transplantation was 176 days (range: 55-4920) for age Conclusion: Overall, our study suggests similar outcomes for elderly patients undergoing allo-HCT as compared to their counterparts, which is in line with prior studies. This likely is due to advancements in the transplant field, including the development of RIC and alternative donors, which have allowed greater access to transplant for older adults. Utilization of allo-HCT is feasible and should be considered for AML/MDS patients ≥65 years. Further research is underway to evaluate the important determinants of health status in older patients undergoing allo-HCT and to ultimately help predict NRM (BMT CTN 1704). Figure 1 Figure 1. Disclosures Bumma: Amgen, Sanofi: Speakers Bureau; Janssen, Oncopeptides, Sanofi: Consultancy. Vasu: Seattle Genetics: Other: travel support; Boehringer Ingelheim: Other: Travel support; Kiadis, Inc.: Research Funding; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Jaglowski: Takeda: Consultancy; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; Novartis: Consultancy, Research Funding. Mims: Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Kura Oncology: Consultancy; Leukemia and Lymphoma Society: Consultancy; Glycomemetics: Research Funding; Aptevo: Research Funding; Xencor: Research Funding; Daiichi-Saynko: Consultancy. Brammer: Celgene: Research Funding; Seattle Genetics: Speakers Bureau; Kymera Therapeutics: Consultancy. Saad: Incyte Pharmaceuticals: Consultancy; careDx: Consultancy; Amgen: Research Funding; Kadmon: Research Funding; OrcaBio: Research Funding; Magenta Therapeutics: Consultancy. de Lima: Miltenyi Biotec: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.
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- 2021
21. Outcomes in Allogeneic Transplant Based on Race and Geographic Location of Residence
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Karilyn Larkin, Audrey M. Sigmund, Qiuhong Zhao, Sarah A Wall, Samantha Jaglowski, Don M. Benson, Yvonne A. Efebera, Justin Jiang, Nicole Grieselhuber, Maria Chaudhry, Patrick Elder, Alice S. Mims, Srinivas Devarakonda, Ashley E. Rosko, Hannah Choe, Sam Penza, Nidhi Sharma, Naresh Bumma, Abdullah Khan, Ayman Saad, Sumithira Vasu, Basem M. William, and Jonathan E. Brammer
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Transplantation ,Race (biology) ,Geography ,Molecular Medicine ,Immunology and Allergy ,Residence ,Cell Biology ,Hematology ,Location ,Demography - Published
- 2021
22. Impact of Bone Marrow Versus Peripheral Blood on Outcomes in Haploidentical Transplantation
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Yvonne A. Efebera, Ashley E. Rosko, Sumithira Vasu, Sam Penza, Nicole Grieselhuber, Sarah A Wall, Karilyn Larkin, Samantha Jaglowski, Alice S. Mims, Maria Chaudhry, Don M. Benson, Audrey M. Sigmund, Srinivas Devarakonda, Qiuhong Zhao, Nidhi Sharma, Hannah Choe, Patrick Elder, Jonathan E. Brammer, Naresh Bumma, Abdullah Khan, Basem M. William, Ayman Saad, and Justin Jiang
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Transplantation ,medicine.medical_specialty ,Haploidentical transplantation ,business.industry ,Cell Biology ,Hematology ,Peripheral blood ,Surgery ,medicine.anatomical_structure ,Molecular Medicine ,Immunology and Allergy ,Medicine ,Bone marrow ,business - Published
- 2021
23. Trends in Survival of AML and MDS Patients Following Allogeneic Transplant
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Yvonne A. Efebera, Hannah Choe, Nicole Grieselhuber, Karilyn Larkin, Jonathan E. Brammer, Ayman Saad, Audrey M. Sigmund, Alice S. Mims, Qiuhong Zhao, Samantha Jaglowski, Sumithira Vasu, Srinivas Devarakonda, Patrick Elder, Maria Chaudhry, Basem M. William, Nidhi Sharma, Sarah A Wall, Sam Penza, Don M. Benson, Ashley E. Rosko, Naresh Bumma, Abdullah Khan, and Justin Jiang
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Published
- 2021
24. Impact of Chronic Graft-Versus-Host Disease on Non-Relapse Mortality and Survival
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Nicole Grieselhuber, Sam Penza, Jonathan E. Brammer, Yvonne A. Efebera, Sumithira Vasu, Maria Chaudhry, Justin Jiang, Audrey M. Sigmund, Hannah Choe, Qiuhong Zhao, Karilyn Larkin, Nidhi Sharma, Sarah A Wall, Alice S. Mims, Ashley E. Rosko, Ayman Saad, Samantha Jaglowski, Don M. Benson, Basem M. William, Srinivas Devarakonda, Patrick Elder, Naresh Bumma, and Abdullah Khan
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Transplantation ,medicine.medical_specialty ,business.industry ,Cell Biology ,Hematology ,medicine.disease ,Gastroenterology ,Graft-versus-host disease ,Internal medicine ,medicine ,Molecular Medicine ,Immunology and Allergy ,Nonrelapse mortality ,business - Published
- 2021
25. Comparison of Bone Marrow Versus Peripheral Blood in Haploidentical Transplantation Using Post-Transplant Cyclophosphamide- a Retrospective Analysis
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Sarah A Wall, Ayman Saad, Yvonne A. Efebera, Srinivas Devarakonda, Don M. Benson, Alice S. Mims, Audrey M. Sigmund, Qiuhong Zhao, Justin Jiang, Samantha Jaglowski, Nicole Grieselhuber, Basem M. William, Nidhi Sharma, Jonathan E. Brammer, Sam Penza, Maria Chaudhry, Patrick Elder, Sumithira Vasu, Ashley E. Rosko, Hannah Choe, Naresh Bumma, and Abdullah Khan
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medicine.medical_specialty ,Platelet Engraftment ,business.industry ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,law.invention ,Transplantation ,Leukemia ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,Cumulative incidence ,Progression-free survival ,business - Abstract
Background: Allogeneic transplantation (allo-HCT) is a potentially curative treatment for a variety of hematologic malignancies and nonmalignant hematologic disorders. Allo-HCT from a haploidentical (Haplo) related donor has emerged as a suitable alternative in the absence of matched related donor (MRD) and matched unrelated donor (MUD). Haplo HCT patients however have higher risk of graft rejection and graft versus-host disease (GVHD). Thus, patients often receive post-transplant cyclophosphamide (PTCy), which has proven to be highly effective in reducing GVHD. While the use of peripheral blood is an attractive option due to the ease of collection and rapid peripheral blood count recovery, not much information is available on the impact of graft sources using PTCy in Haplo-HCT. This study compares outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for Haplo-HCT in adult patients. Methods: We performed a retrospective study of 81 adult patients who underwent Haplo-HCT at The Ohio State University from 2009 to 2018. The study endpoints were overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse, engraftment, acute GVHD (grade II-IV), and chronic GVHD. All endpoints were measured from the time of transplantation. Patient, disease, and transplant-related characteristics were compared between the two groups (BM versus PB) using the Mann-Whitney U test for continuous variables, and chi-squared or Fisher's exact test for categorical variables. The probabilities of OS and PFS were calculated using the Kaplan-Meier (KM) method and compared using log-rank test. Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: We compared the outcomes of patients who received a BM graft (N=43) with those receiving a PB graft (N=38). The median age at transplant was 57 years (20-74). All patients received PTCy in addition to tacrolimus and mycophenolate in 91% of patients. Reduced intensity conditioning (RIC) was used in majority of patients (N=63, 78%). The two groups were comparable including age (median, 60 years for BM and 56 years for PB, p=0.60) and the type of conditioning regimen (79% RIC for BM, 76% RIC for PB, p=0.77). The number of CD34+ and CD3+ infused cells was higher in PB grafts (median, 8.6x106 CD34+ cells/Kg, 2.0 x108 CD3+ cells/Kg, respectively) than for BM (median, 3.7x106 CD34+cells/Kg, 0.4x108 CD3+cells/Kg, respectively). Time to neutrophil and platelet engraftment were significantly shorter in patients receiving PB versus those getting BM grafts: median 15 vs. 17.5 days, (p=0.02) and median 20 vs. 29 days (p Conclusion: Our study suggests peripheral blood for haploidentical transplant to be a good alternative to bone marrow. Similar PFS, OS and NRM were seen between the two graft sources. As expected, faster neutrophil and platelets engraftment were seen with PB due to more CD3+ and CD34+ infused, but without an increase in acute or chronic GVHD. A reduced relapse risk was observed with PB graft. Our study is small and is retrospective, but provide encouraging results. A prospective randomized controlled trial is required to confirm these results. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy. William:Seattle Genetics: Research Funding; Merck: Research Funding; Dova: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Guidepoint Global: Consultancy; Incyte: Research Funding; Celgene: Consultancy, Honoraria. Mims:Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Amgen: Other: research support; Magenta Therapeutics: Other: Personal Fees; Incyte Pharmaceuticals: Other: Personal Fees; Orcabio: Other: research support; Kadmon: Other: research support. Efebera:Celgene: Research Funding; Ohio State University: Current Employment; Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding.
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- 2020
26. Impact of Race and Geographic Location on Outcomes in Allogeneic Transplant
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Alice S. Mims, Audrey M. Sigmund, Sarah A Wall, Qiuhong Zhao, Ashley E. Rosko, Nicole Grieselhuber, Don M. Benson, Srinivas Devarakonda, Justin Jiang, Hannah Choe, Nidhi Sharma, Jonathan E. Brammer, Patrick Elder, Naresh Bumma, Abdullah Khan, Samantha Jaglowski, Sam Penza, Maria Chaudhry, Basem M. William, Ayman Saad, Sumithira Vasu, Karilyn Larkin, and Yvonne A. Efebera
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Referral ,business.industry ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Health equity ,Underserved Population ,Cohort ,Medicine ,Residence ,Progression-free survival ,Rural area ,business ,Demography - Abstract
Introduction: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of both malignant and nonmalignant hematologic disorders. However, allo-HCT is costly and requires highly specialized, technologically advanced care that is only available in select healthcare centers across the country. Due to its cost and limited availability, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Prior studies have focused on the impact of health disparities, including race, and geographic residence at time of transplant, on allo-HCT outcomes with variable results. The aim of this study was to evaluate the impact of race and location of residence on outcomes of allo-HCT at one major referral institution. Methods: We performed a retrospective cohort study of patients that underwent allo-HCT at the Ohio State University from 1984 to 2018. The impact of demographic factors including race and place of primary residence were assessed. Patients were divided into race defined as Caucasian, African American (AA), and other. They were also grouped by zip code into rural, suburban, and urban groups. Rural was defined as less than 1000 people per square mile, suburban between 1000-3000 people per square mile, and urban greater than 3000 people per square mile. 2018 population estimates were used. Patients were then stratified into 7 groups based on year (yr) of transplant for analysis. Group (gp) 1 included 1984-1988, gp 2 1989-1993, gp 3 1994-1998, gp 4 1999-2003, gp 5 2004-2008, gp 6 2009-2013, and gp 7 2014-2018. Primary endpoints were progression free survival (PFS) and overall survival (OS). PFS and OS were calculated using Kaplan Meier Curves and compared using log-rank test between race and residence groups. Results: A total of 1,943 patients were included in the study. Of these patients, median age at time of transplant was 50 years old (range 18-76), and 59.6% were male. AML/MDS patients made up the majority of the cohort at 46.3%, with the other most common diagnoses being non-Hodgkin's lymphoma (14.2%), acute lymphocytic leukemia (11.8%), and chronic myeloid leukemia (10.1%). Most patients (94.3%) identified as Caucasian, while 4.6% identified as AA, and 1.1% other. The majority of patients lived in a rural area at the time of transplant with 63.4% rural, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS between Caucasian and AA patients (Figure 1A and B; p=0.15, 0.21). Median OS for AA was 1.9 yrs [95% confidence interval (CI): 0.8-3.6] as compared to 2.3 yrs (95% CI: 1.9-2.9) for Caucasians, with 5 -yr OS of 33 vs. 42% and 10-yr OS of 21 vs. 36% for AA and Caucasian, respectively. Median PFS was 0.9 (95% CI: 0.5-2.7) and 1.3 yrs (95% CI 1.1-1.6), with 5 -yr PFS of 30 vs. 37% and 10-yr PFS of 21 vs. 32% for AA and Caucasian, respectively. There also was no significant difference in OS or PFS between rural, urban, and suburban patients (Figure 2A and 2B; p=0.39, 0.17), with median OS in the three groups 2.2 (95%CI: 1.7-2.9), 2.9 (95%CI: 1.6-4.5), and 2.2 (95% CI: 1.6-3.6) yrs, and 5-yr OS of 40 vs. 43 vs. 43% and 10-yr OS of 33 vs. 39 vs. 39%, respectively. Median PFS were 2.2 (95%CI: 1.7-2.9), 2.9 (95%CI: 1.6-4.5), and 2.2 yrs [95% CI: 1.6-3.6], with 5-yr PFS of 36 vs. 40 vs. 38% and 10-yr PFS of 30 vs. 37 vs. 35%, respectively. Conclusion: Our study suggests that once patients undergo allo-HCT, there is no significant difference in outcomes between patients based on race or residence. This finding suggests that while these underserved populations may initially have less access to specialized care for HCT, if they ultimately undergo allo-HCT, outcomes are similar to their counterparts. Our study did show a significantly lower rates of allo-HCT performed in non-Caucasian races (94% Caucasians vs 4.6% AA and 1% other), which may reflect disparities in access to care in these groups as well as a lack of donors. Further research is needed to assess the barriers for these underserved patients to undergo transplant and to help ameliorate these barriers. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees; Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University. Jaglowski:Kite, a Gilead Company: Consultancy, Research Funding; Juno: Consultancy; Novartis: Consultancy, Research Funding; CRISPR: Consultancy. William:Merck: Research Funding; Celgene: Consultancy, Honoraria; Dova: Research Funding; Seattle Genetics: Research Funding; Incyte: Research Funding; Guidepoint Global: Consultancy; Kyowa Kirin: Consultancy, Honoraria. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Novartis: Speakers Bureau; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board. Brammer:Seattle Genetics, Inc.: Speakers Bureau; Celgene Corporation: Research Funding. Efebera:Celgene: Research Funding; Pharmacyclics: Research Funding; Takeda: Honoraria, Speakers Bureau; Ohio State University: Current Employment.
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- 2020
27. Biodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo
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Min Gao, Weiyu Zhao, Xinfu Zhang, Yizhou Dong, Chengxiang Zhang, Bin Li, Xiaofang Chen, Justin Jiang, and Xiao Luo
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0301 basic medicine ,Materials science ,Nanotechnology ,02 engineering and technology ,Esterase ,Article ,Nanomaterials ,Mice ,03 medical and health sciences ,In vivo ,Animals ,General Materials Science ,RNA, Messenger ,Gene Editing ,Messenger RNA ,Cas9 ,Esters ,Biodegradation ,Safe delivery ,021001 nanoscience & nanotechnology ,Combinatorial chemistry ,In vitro ,Nanostructures ,030104 developmental biology ,CRISPR-Cas Systems ,0210 nano-technology - Abstract
Efficient and safe delivery of the CRISPR/Cas system is one of the key challenges for genome-editing applications in humans. Herein, we designed and synthesized a series of biodegradable lipidlike compounds containing ester groups for the delivery of mRNA-encoding Cas9. Two lead materials, termed N-methyl-1,3-propanediamine (MPA)-A and MPA-Ab, showed a tunable rate of biodegradation. MPA-A with linear ester chains was degraded dramatically faster than MPA-Ab with branched ester chains in the presence of esterase or in wild-type mice. Most importantly, MPA-A and MPA-Ab demonstrated efficient delivery of Cas9 mRNA both in vitro and in vivo. Consequently, these biodegradable lipidlike nanomaterials merit further development as genome-editing delivery tools for biological and therapeutic applications.
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- 2017
28. Longitudinal Survival Outcomes in Allogeneic Stem Cell Transplantation: An Institutional Experience
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Sarah A Wall, Nicole Grieselhuber, Ayman Saad, Karilyn Larkin, Nidhi Sharma, Srinivas Devarakonda, Alice S. Mims, Justin Jiang, Don M. Benson, Basem M. William, Yvonne A. Efebera, Audrey M. Sigmund, Qiuhong Zhao, Hannah Choe, Naresh Bumma, Abdullah Khan, Patrick Elder, Jonathan E. Brammer, Sam Penza, Maria Chaudhry, Samantha Jaglowski, Sumithira Vasu, and Ashley E. Rosko
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Oncology ,Transplantation ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology ,Stem cell ,business - Published
- 2021
29. Trend in Survival in Patients Undergoing Allogeneic Stem Cell Transplantation: An Institutional Experience
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Don M. Benson, Srinivas Devarakonda, Ayman Saad, Karilyn Larkin, Jonathan E. Brammer, Nicole Grieselhuber, Yvonne A. Efebera, Patrick Elder, Audrey M. Sigmund, Qiuhong Zhao, Sam Penza, Justin Jiang, Maria Chaudhry, Nidhi Sharma, Ashley E. Rosko, Basem M. William, Naresh Bumma, Abdullah Khan, Sumithira Vasu, Samantha Jaglowski, Hannah Choe, Alice S. Mims, and Sarah A Wall
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Disease ,Biochemistry ,Transplantation ,Family medicine ,medicine ,Data monitoring committee ,Chronic gvhd ,In patient ,Cumulative incidence ,Progression-free survival ,business - Abstract
Introduction: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many hematological malignancies and disorders. However, this potential is often impeded by several factors including relapse of the underlying disease, graft-vs-host disease (GVHD) and infectious complications. Specifically, acute GVHD continues to be a major factor in the morbidity and mortality of patients. Hence, the practice of allo-SCT is continuously evolving to mitigate these factors. In particular, advances in the conditioning regimens, GVHD prophylaxis, infectious disease monitoring and prophylaxis and supportive care not only have resulted in improved outcomes, but also have expanded potential indications for allo-HSCT. Therefore, we conducted a retrospective analysis on patients who underwent allo-SCT at The Ohio State University from 1986-2018 to better understand how survival has changed longitudinally in accordance with these therapeutic advancements. Method: We analyzed data from 1943 consecutive patients who received an allo-SCT. Patients were divided into seven groups based on the year of transplant: groups (gp) 1: 1984-1988, 2: 1989-1993, 3: 1994-1998, 4: 1999-2003, 5: 2004-2008, 6: 2009-2013, and 7: 2014-2018. The primary endpoints were overall survival (OS) and progression free survival (PFS), and log-rank test was used to compare across transplant years. The Kaplan-Meier method was used to estimate OS and PFS. The secondary endpoints were the cumulative incidences of grade II-IV and grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), and non-relapse mortality (NRM). Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: Across the years (1984-2018), the median age was 50.0 (range: 18-76) with 59.6% of the patients being male. Acute myeloid leukemia accounted for 36.3% of transplants, followed by non-Hodgkin lymphoma (14.2%), acute lymphoid leukemia (11.8%), chronic myeloid leukemia (10.1%), and myelodysplastic syndrome (10.0%). Fifty-five percent of patients received myeloablative conditioning. Across the groups, statistically significant improvements in PFS and OS were observed (p Conclusion: Our data shows improved overall and progression-free survival post allo-SCT over decades, which may be attributed to advances in supportive care, and GVHD and relapse mitigation therapy. The decline in NRM is also likely due to improved supportive measures such as infectious disease monitoring and prophylaxis. Nonetheless, post-transplant relapse and grade III-IV aGVHD remain prominent challenges. Therefore, future research should continue to investigate therapeutic strategies that can both reduce high grade GVHD while limiting post-transplant relapse. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:CRISPR: Consultancy; Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. William:Incyte: Research Funding; Guidepoint Global: Consultancy; Dova: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Mims:Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Incyte Pharmaceuticals: Other: Personal Fees; Amgen: Other: research support; Kadmon: Other: research support; Orcabio: Other: research support; Magenta Therapeutics: Other: Personal Fees. Efebera:Celgene: Research Funding; Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Ohio State University: Current Employment.
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- 2020
30. Improvement in Survival of AML and MDS Patients Following Allogeneic Transplant: A Long-Term Institutional Experience
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Hannah Choe, Nicole Grieselhuber, Sarah A Wall, Don M. Benson, Alice S. Mims, Karilyn Larkin, Audrey M. Sigmund, Srinivas Devarakonda, Qiuhong Zhao, Patrick Elder, Ashley E. Rosko, Samantha Jaglowski, Justin Jiang, Yvonne A. Efebera, Sumithira Vasu, Sam Penza, Naresh Bumma, Abdullah Khan, Maria Chaudhry, Nidhi Sharma, Ayman Saad, Basem M. William, and Jonathan E. Brammer
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Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Immunology ,medicine ,Cell Biology ,Hematology ,business ,Biochemistry ,Term (time) - Abstract
Introduction: Allogeneic stem cell transplant (allo-SCT) plays a key role in the post-remission therapy for acute myeloid leukemia (AML) patients due to its high rates of efficacy as compared to alternate therapies. For patients with relapsed/refractory AML and those with high-risk myelodysplastic syndrome (MDS), it remains the sole curative option. However, these patients continue to have significant obstacles for successful transplant including risk for relapse of underlying disease, graft versus host disease (GVHD), and infectious complications. Outcomes of allo-SCT in these patients have improved over time with the evolution of practice of allo-SCT, including modifications of transplant conditioning regimens, supportive care, and earlier recognition of transplant complications. Our study sought to assess the trends in survival in AML and MDS patients undergoing allogeneic transplant at The Ohio State University from 1984-2018. Methods: We analyzed data from 900 consecutive patients who received an allo-SCT (705 AML and 195 MDS). The patients were stratified into 7 different groups based on year of transplant using 5 year increments; group (gp) 1 included 1984-1988, gp 2 1989-1993, gp 3 1994-1998, gp 4 1999-2003, gp 5 2004-2008, gp 6 2009-2013, and gp 7 2014-2018. Progression free survival (PFS) and overall survival (OS) were utilized as primary end points. PFS and OS were calculated using Kaplan Meier Curves. Secondary endpoints included cumulative incidences of grade II-IV and III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), and non-relapse mortality (NRM). Cumulative incidence rates were estimated and compared using Gray's test accounting for competing risks. Results: Median age at transplant was 52 years (yrs) old (range 18-76) and 55.6% were male. Patients having myeloablative (MA) conditioning regimen comprised 57.6% of the cohort. From 1984 to 2018, there was a statistically significant improvement in both PFS and OS (Figure 1 a and b; p Conclusion: Our study demonstrates significant improvement over the past several decades in survival in AML and MDS patients undergoing allo-SCT. Major factors that likely contribute to improvement in outcomes throughout the years include adjustments in conditioning regimens and GVHD prophylaxis, earlier recognition of complications as well as improved management, and improved general supportive care. Overall, while outcomes have improved significantly throughout the years, post-transplant relapses remains the leading cause of transplant failure in this group. Preventing relapse post-transplant represents a continued target for research today. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Omeros: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University. Jaglowski:CRISPR: Consultancy; Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. William:Kyowa Kirin: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Guidepoint Global: Consultancy; Incyte: Research Funding; Seattle Genetics: Research Funding; Merck: Research Funding; Dova: Research Funding. Mims:Novartis: Speakers Bureau; Agios: Consultancy; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board. Brammer:Seattle Genetics, Inc.: Speakers Bureau; Celgene Corporation: Research Funding. Efebera:Celgene: Research Funding; Pharmacyclics: Research Funding; Takeda: Honoraria, Speakers Bureau; Ohio State University: Current Employment.
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- 2020
31. Impact of Chronic Graft-Versus-Host Disease on Non-Relapse Mortality
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Yvonne A. Efebera, Sam Penza, Jonathan E. Brammer, Sarah A Wall, Nicole Grieselhuber, Alice S. Mims, Basem M. William, Maria Chaudhry, Patrick Elder, Karilyn Larkin, Don M. Benson, Sumithira Vasu, Ayman Saad, Samantha Jaglowski, Srinivas Devarakonda, Audrey M. Sigmund, Qiuhong Zhao, Hannah Choe, Ashley E. Rosko, Naresh Bumma, Abdullah Khan, Nidhi Sharma, and Justin Jiang
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medicine.medical_specialty ,education.field_of_study ,business.industry ,medicine.medical_treatment ,Incidence (epidemiology) ,Immunology ,Hazard ratio ,Population ,Retrospective cohort study ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Disease ,Biochemistry ,Quality of life ,hemic and lymphatic diseases ,Family medicine ,Medicine ,Data monitoring committee ,business ,education - Abstract
Introduction-Chronic graft-versus-host disease (cGVHD) poses as a major late complication of hematopoietic stem cell transplantation. The role of cGVHD as a determinant in transplant-related morbidity and mortality, infectious complications, prolonged immune suppression, and impaired patient-reported quality of life has been extensively studied. Nonetheless, numerous advances in allogeneic hematopoietic stem cell transplant (allo-SCT) in recent years have expanded the indications for allo-SCT to a broader range of patients, including previously excluded older patients. However, long-term health status of older transplant recipients is poorly studied. Notably, the incidence of cGVHD may increase with age. Therefore, the development of cGVHD and the use of immunosuppressive therapy may lead to a higher degree of non-relapse mortality (NRM) in older patients. The objective of this study was to compare the NRM in both younger and older transplant recipients with and without cGVHD. Methods-We performed a retrospective cohort study of patients that underwent allo-SCT at the Ohio State University from 1999 to 2018. Data was analyzed from 1194 patients who survived or have been followed up with by at least day (d) 180 post-transplantation, among which 373 patients had developed cGVHD. Patients were grouped based on their age into a younger and older population. The older population was defined as ≥60 (N=373, 31%) with the younger population defined as Results-The median age at allo-SCT was 53.0 yr (range: 18-76) and 61.1% were male. Acute myeloid leukemia accounted for 36.7% of transplants, followed by non-Hodgkin's lymphoma (14.8%), acute lymphoid leukemia (12.7%), and myelodysplastic syndrome (11.0%). Additionally, 58.0% received reduced-intensity conditioning regimen. The majority of stem cell donor types were match unrelated (45.3%) and match related (39.8%). Patients who had developed cGVHD by d180, regardless of age, were at higher risk of NRM compared to patients with no cGVHD (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.16-1.99; p=0.002). To examine the influence of age with NRM, we stratified the analysis by cGVHD status by d180. Among patients developed cGVHD by d180, in both univariable (HR 1.22, 95% CI 0.79-1.9, p=0.373) and multivariable analysis (HR: 1.17, 95% CI: 0.74-1.87; p=0.501), there was no statistically significant difference in NRM between patients ≥60 and Conclusion-This study showed that patients with cGVHD by day 180 were at higher risk for higher NRM compared to patients without cGVHD. Among cGVHD patients, there was no difference on the outcome of older patients (≥60 years old) compared to younger ones ( Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy. William:Celgene: Consultancy, Honoraria; Dova: Research Funding; Guidepoint Global: Consultancy; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Seattle Genetics: Research Funding; Incyte: Research Funding. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Novartis: Speakers Bureau; Agios: Consultancy. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Magenta Therapeutics: Other: Personal Fees; Incyte Pharmaceuticals: Other: Personal Fees; Amgen: Other: research support; Kadmon: Other: research support; Orcabio: Other: research support. Efebera:Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Celgene: Research Funding; Ohio State University: Current Employment.
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- 2020
32. A Hybridde novoAssembly of the Sea Pansy (Renilla muelleri) Genome
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Estefanía Rodríguez, Catherine S. McFadden, Andrea M. Quattrini, Justin Jiang, Joseph F. Ryan, and Warren R. Francis
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0106 biological sciences ,Renilla ,food.ingredient ,Octocorallia ,Gene prediction ,Sequence assembly ,Health Informatics ,Genomics ,Nematostella ,Augustus ,Data Note ,01 natural sciences ,Genome ,octocoral ,03 medical and health sciences ,food ,hybrid assembly ,Anthozoa ,Animals ,030304 developmental biology ,PacBio ,Comparative genomics ,0303 health sciences ,biology ,Computational Biology ,High-Throughput Nucleotide Sequencing ,Starlet sea anemone ,Molecular Sequence Annotation ,biology.organism_classification ,Computer Science Applications ,MaSuRCA ,Evolutionary biology ,gene prediction ,010606 plant biology & botany - Abstract
BackgroundOver 3,000 species of octocorals (Cnidaria, Anthozoa) inhabit an expansive range of environments, from shallow tropical seas to the deep-ocean floor. They are important foundation species that create coral “forests” which provide unique niches and three-dimensional living space for other organisms. The octocoral genusRenillainhabits sandy, continental shelves in the subtropical and tropical Atlantic and eastern Pacific Oceans.Renillais especially interesting because it produces secondary metabolites for defense, exhibits bioluminescence, and produces a luciferase that is widely used in dual-reporter assays in molecular biology. Although several cnidarian genomes are currently available, the majority are from hexacorals. Here, we present ade novoassembly of theR. muellerigenome, making this the first complete draft genome from an octocoral.FindingsWe generated a hybridde novoassembly using the Maryland Super-Read Celera Assembler v.3.2.6 (MaSuRCA). The final assembly included 4,825 scaffolds and a haploid genome size of 172 Mb. A BUSCO assessment found 88% of metazoan orthologs present in the genome. An Augustusab initiogene prediction found 23,660 genes, of which 66% (15,635) had detectable similarity to annotated genes from the starlet sea anemone,Nematostella vectensis,or to the Uniprot database. Although theR. muellerigenome is smaller (172 Mb) than other publicly available, hexacoral genomes (256-448 Mb), theR. muellerigenome is similar to the hexacoral genomes in terms of the number of complete metazoan BUSCOs and predicted gene models.ConclusionsTheR. muellerihybrid genome provides a novel resource for researchers to investigate the evolution of genes and gene families within Octocorallia and more widely across Anthozoa. It will be a key resource for future comparative genomics with other corals and for understanding the genomic basis of coral diversity.
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- 2018
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33. [Research on Rapid and Non-Destructive Identification of Aging Wheat Based on ATR-Terahertz Spectroscopy Combined with PLS-DA]
- Author
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Dong, Wang, Li-gang, Pan, Long-hai, Liu, Justin, Jiang, An, Li, Xin-xin, Jin, Zhi-hong, Ma, and Ji-hua, Wang
- Abstract
In this research, the terahertz spectra data of the aging wheat processed under manual control environment by ATR accessory were collected. After the data diversity based on the composite score by PCA, the non-destructive identification models of aging wheat were developed by PLS-DA algorithm. The results showed that for the absorption coefficient spectrum, the accuracy of the experimental group, control group of the calibration set and cross validation set were 84.2%, 94.7%, 84.2% and 81.6% respectively, while the accuracy of the experimental group and control group of the external validation set were 73.7% and 100.0% respectively; for the refractive index spectrum, the accuracy of the experimental group, control group of the calibration set and cross validation set were 84.2%, 92.0%, 76.3% and 76.3% respectively, while the accuracy of the experimental group and control group of the external validation set were 84.2% and 89.5% respectively. The research indicates that ATR-THz technology should be of great potentials in the application in the non-destructive identification of aging wheat.
- Published
- 2018
34. Unbiased roughness measurements: the key to better etch performance
- Author
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Nader Shamma, Chris Mack, Justin Jiang, Rich Wise, Liu Yang, Andrew Liang, Jengyi Yu, Liang Chen-Wei, Diane J. Hymes, and Stephen M. Sirard
- Subjects
Scanner ,Materials science ,business.industry ,Extreme ultraviolet lithography ,02 engineering and technology ,Surface finish ,Edge (geometry) ,021001 nanoscience & nanotechnology ,01 natural sciences ,Metrology ,010309 optics ,Optics ,Resist ,Stack (abstract data type) ,0103 physical sciences ,0210 nano-technology ,business ,Smoothing - Abstract
Edge placement error (EPE) has become an increasingly critical metric to enable Moore’s Law scaling. Stochastic variations, as characterized for lines by line width roughness (LWR) and line edge roughness (LER), are dominant factors in EPE and known to increase with the introduction of EUV lithography. However, despite recommendations from ITRS, NIST, and SEMI standards, the industry has not agreed upon a methodology to quantify these properties. Thus, differing methodologies applied to the same image often result in different roughness measurements and conclusions. To standardize LWR and LER measurements, Fractilia has developed an unbiased measurement that uses a raw unfiltered line scan to subtract out image noise and distortions. By using Fractilia’s inverse linescan model (FILM) to guide development, we will highlight the key influences of roughness metrology on plasma-based resist smoothing processes. Test wafers were deposited to represent a 5 nm node EUV logic stack. The patterning stack consists of a core Si target layer with spin-on carbon (SOC) as the hardmask and spin-on glass (SOG) as the cap. Next, these wafers were exposed through an ASML NXE 3350B EUV scanner with an advanced chemically amplified resist (CAR). Afterwards, these wafers were etched through a variety of plasma-based resist smoothing techniques using a Lam Kiyo conductor etch system. Dense line and space patterns on the etched samples were imaged through advanced Hitachi CDSEMs and the LER and LWR were measured through both Fractilia and an industry standard roughness measurement software. By employing Fractilia to guide plasma-based etch development, we demonstrate that Fractilia produces accurate roughness measurements on resist in contrast to an industry standard measurement software. These results highlight the importance of subtracting out SEM image noise to obtain quicker developmental cycle times and lower target layer roughness.
- Published
- 2018
35. GlcNAc Conjugated Atorvastatin with Enhanced Water Solubility and Cellular Internalization
- Author
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Justin Jiang, Wenqing Li, Xiaofang Chen, Xiao Luo, Xinfu Zhang, Chunxi Zeng, Bin Li, Yizhou Dong, and Weiyu Zhao
- Subjects
0301 basic medicine ,media_common.quotation_subject ,Atorvastatin ,Biomedical Engineering ,Pharmaceutical Science ,Bioengineering ,Conjugated system ,Reductase ,01 natural sciences ,Article ,Acetylglucosamine ,Cell Line ,03 medical and health sciences ,Structure-Activity Relationship ,medicine ,Structure–activity relationship ,Humans ,Solubility ,Internalization ,media_common ,Pharmacology ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Water ,Biological Transport ,Ligand (biochemistry) ,0104 chemical sciences ,030104 developmental biology ,Biochemistry ,Drug delivery ,Biotechnology ,medicine.drug - Abstract
Targeting ligands facilitate cell specific drug delivery and improve pharmaceutical properties. Herein, we designed two ligand drug conjugates by conjugating GlcNAc (N-acetylglucosamine) with atorvastatin. These two conjugates, termed G-AT and G-K-AT, exhibited enhanced water solubility and cellular uptake. Moreover, both G-AT and G-K-AT were able to release atorvastatin and consequently achieve significant inhibition against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase.
- Published
- 2017
36. GlcNAc Conjugated Atorvastatin with Enhanced Water Solubility and Cellular Internalization.
- Author
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Xinfu Zhang, Xiaofang Chen, Weiyu Zhao, Chunxi Zeng, Xiao Luo, Wenqing Li, Bin Li, Justin Jiang, and Yizhou Dong
- Published
- 2017
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