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Item Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19–Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults — VISION Network, Nine States, September–November 2022(Center for Disease Control, 2022-12-30) Tenforde, Mark W.; Weber, Zachary A.; Natarajan, Karthik; Klein, Nicola P.; Kharbanda, Anupam B.; Stenehjem, Edward; Embi, Peter J.; Reese, Sarah E.; Naleway, Allison L.; Grannis, Shaun J.; DeSilva, Malini B.; Ong, Toan C.; Gaglani, Manjusha; Han, Jungmi; Dickerson, Monica; Fireman, Bruce; Dascomb, Kristin; Irving, Stephanie A.; Vazquez-Benitez, Gabriela; Rao, Suchitra; Konatham, Deepika; Patel, Palak; Schrader, Kristin E.; Lewis, Ned; Grisel, Nancy; McEvoy, Charlene; Murthy, Kempapura; Griggs, Eric P.; Rowley, Elizabeth A. K.; Zerbo, Ousseny; Arndorfer, Julie; Dunne, Margaret M.; Goddard, Kristin; Ray, Caitlin; Zhuang, Yan; Timbol, Julius; Najdowski, Morgan; Yang, Duck-Hye; Hansen, John; Ball, Sarah W.; Link-Gelles, Ruth; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and EngineeringDuring June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 31% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 57% compared with no vaccination, 38% compared with monovalent vaccination only with last dose 5-7 months earlier, and 45% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.Item Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19–Associated Hospitalizations Among Immunocompromised Adults — Nine States, January–September 2021(CDC, 2021-11) Embi, Peter J.; Levy, Matthew E.; Naleway, Allison L.; Patel, Palak; Gaglani, Manjusha; Natarajan, Karthik; Dascomb, Kristin; Ong, Toan C.; Klein, Nicola P.; Liao, I-Chia; Grannis, Shaun J.; Han, Jungmi; Stenehjem, Edward; Dunne, Margaret M.; Lewis, Ned; Irving, Stephanie A.; Rao, Suchitra; McEvoy, Charlene; Bozio, Catherine H.; Murthy, Kempapura; Dixon, Brian E.; Grisel, Nancy; Yang, Duck-Hye; Goddard, Kristin; Kharbanda, Anupam B.; Reynolds, Sue; Raiyani, Chandni; Fadel, William F.; Arndorfer, Julie; Rowley, Elizabeth A.; Fireman, Bruce; Ferdinands, Jill; Valvi, Nimish R.; Ball, Sarah W.; Zerbo, Ousseny; Griggs, Eric P.; Mitchell, Patrick K.; Porter, Rachael M.; Kiduko, Salome A.; Blanton, Lenee; Zhuang, Yan; Steffens, Andrea; Reese, Sarah E.; Olson, Natalie; Williams, Jeremiah; Dickerson, Monica; McMorrow, Meredith; Schrag, Stephanie J.; Verani, Jennifer R.; Fry, Alicia M.; Azziz-Baumgartner, Eduardo; Barron, Michelle A.; Thompson, Mark G.; DeSilva, Malini B.; Medicine, School of MedicineWhat is already known about this topic? Studies suggest that immunocompromised persons who receive COVID-19 vaccination might not develop high neutralizing antibody titers or be as protected against severe COVID-19 outcomes as are immunocompetent persons. What is added by this report? Effectiveness of mRNA vaccination against laboratory-confirmed COVID-19–associated hospitalization was lower (77%) among immunocompromised adults than among immunocompetent adults (90%). Vaccine effectiveness varied considerably among immunocompromised patient subgroups. What are the implications for public health practice? Immunocompromised persons benefit from COVID-19 mRNA vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations, practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.Item Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings(Massachusetts Medical Society, 2021-10-07) Thompson, Mark G.; Stenehjem, Edward; Grannis, Shaun; Ball, Sarah W.; Naleway, Allison L.; Ong, Toan C.; DeSilva, Malini B.; Natarajan, Karthik; Bozio, Catherine H.; Lewis, Ned; Dascomb, Kristin; Dixon, Brian E.; Birch, Rebecca J.; Irving, Stephanie A.; Rao, Suchitra; Kharbanda, Elyse; Han, Jungmi; Reynolds, Sue; Goddard, Kristin; Grisel, Nancy; Fadel, William F.; Levy, Matthew E.; Ferdinands, Jill; Fireman, Bruce; Arndorfer, Julie; Valvi, Nimish R.; Rowley, Elizabeth A.; Patel, Palak; Zerbo, Ousseny; Griggs, Eric P.; Porter, Rachael M.; Demarco, Maria; Blanton, Lenee; Steffens, Andrea; Zhuang, Yan; Olson, Natalie; Barron, Michelle; Shifflett, Patricia; Schrag, Stephanie J.; Verani, Jennifer R.; Fry, Alicia; Gaglani, Manjusha; Azziz-Baumgartner, Eduardo; Klein, Nicola P.; Family Medicine, School of MedicineBACKGROUND There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS We conducted a study involving adults (≥50 years of age) with Covid-19–like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients’ vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19–associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. Methods: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. Results: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. Conclusions: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).Item Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells(Wiley, 2015-12) Zhuang, Yan; Nguyen, Hong T.; Burow, Matthew E.; Zhuo, Ying; El-Dahr, Samir S.; Yao, Xiao; Cao, Subing; Flemington, Erik K.; Nephew, Kenneth P.; Fang, Fang; Collins-Burow, Bridgette; Rhodes, Lyndsay V.; Yu, Qiang; Jayawickramarajah, Janarthanan; Shan, Bin; Department of Medicine, IU School of MedicineEpigenetic regulation of gene expression is critical to phenotypic maintenance and transition of human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) is a long intergenic non-coding RNA that epigenetically represses gene expression via recruitment of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase. Elevated expression of HOTAIR promotes progression of breast cancer. In the current study we examined the expression and function of HOTAIR in MCF-7-TNR cells, a derivative of the luminal-like breast cancer cell line MCF-7 that acquired resistance to TNF-α-induced cell death. The expression of HOTAIR, markers of the luminal-like and basal-like subtypes, and growth were compared between MCF-7 and MCF-7-TNR cells. These variables were further assessed upon inhibition of HOTAIR, EZH2, p38 MAPK, and SRC kinase in MCF-7-TNR cells. When compared with MCF-7 cells, MCF-7-TNR cells exhibited an increase in the expression of HOTAIR, which correlated with characteristics of a luminal-like to basal-like transition as evidenced by dysregulated gene expression and accelerated growth. MCF-7-TNR cells exhibited reduced suppressive histone H3 lysine27 trimethylation on the HOTAIR promoter. Inhibition of HOTAIR and EZH2 attenuated the luminal-like to basal-like transition in terms of gene expression and growth in MCF-7-TNR cells. Inhibition of p38 and SRC diminished HOTAIR expression and the basal-like phenotype in MCF-7-TNR cells. HOTAIR was robustly expressed in the native basal-like breast cancer cells and inhibition of HOTAIR reduced the basal-like gene expression and growth. Our findings suggest HOTAIR-mediated regulation of gene expression and growth associated with the basal-like phenotype of breast cancer cells.Item Promoting TEFCA with Blockchain Technology: A Decentralized Approach to Patient-centered Healthcare Data Management(AMIA, 2023) Zhuang, Yan; Zhang, Luxia; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and EngineeringThe Trusted Exchange Framework and Common Agreement (TEFCA) is a framework consisting of seven principles designed to create a secure and seamless health information exchange system across various healthcare settings. The ultimate goal of TEFCA is to facilitate public health surveillance, increase interoperability, promote data sharing, and ensure patient-centered healthcare data management. While the implementation of these principles is challenging, blockchain technology, with its unique features such as transparency, auditability, immutability, and anonymity, can provide a promising solution to the development of TEFCA. This article delves into the potential of blockchain technology to promote TEFCA design. By providing an immutable and transparent ledger, blockchain ensures data integrity, openness, and patient privacy. Overall, the use of blockchain technology can help address the challenges of implementing TEFCA principles and promote patient empowerment and control over their health data, improve data interoperability, and enhance healthcare quality.Item Self-sovereign identity empowered non-fungible patient tokenization for health information exchange using blockchain technology(Elsevier, 2023-05) Zhuang, Yan; Shyu, Chi-Ren; Hong, Shenda; Li, Pengfei; Zhang, Luxia; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and EngineeringBackground: Patient tokenization is a novel approach that allows anonymous patient-level linkage across healthcare facilities, minimizing the risk of breaching protected health information in health information exchange (HIE). Most patient tokenization is the centralized approach that is unable to address data security concerns fundamentally. Non-Fungible Tokens (NFT), which are non-transferable cryptographic assets on the blockchain, have the potential to provide secure, decentralized, and trustworthy patient tokenization. Self-Sovereign Identity (SSI) is a user-centric approach to verify the ownership of NFTs in a decentralized manner. Methods We have developed a blockchain architecture that contains four modules: (1) Creation module for NFTs creation, (2) Linkage module to link the local patients' accounts to their NFTs, (3) Authentication module that allows patients to permit healthcare providers to access their token, and (4) Exchange module, which involves the HIE process and the validation of the legitimacy of the token through SSI. Results A case study has been conducted on the proposed architecture. Over 3 million transactions have been completed successfully with a blockchain validation and written time of 1.17 s on average. A stability test has also been conducted with a higher throughput of 200 transactions per second running for an hour with an average transaction processing time of 1.42 s. Conclusions This study proposed a blockchain architecture that achieves SSI-enabled NFT-based patient tokenization. Our architecture design, implementation, and case studies have demonstrated the feasibility and potential of NFT with SSI to establish a secure, transparent, and patient-centric identity management and HIE.