IU Indianapolis ScholarWorks :: Browsing by Author "Liu, Yuan"

Browsing by Author "Liu, Yuan"

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Acute toxicity in comprehensive head and neck radiation for nasopharynx and paranasal sinus cancers: cohort comparison of 3D conformal proton therapy and intensity modulated radiation therapy.
(BMC, 2016) McDonald, Mark W.; Liu, Yuan; Moore, Michael G.; Johnstone, Peter A. S.; Department of Otolaryngology--Head & Neck Surgery, IU School of Medicine
Background: To evaluate acute toxicity endpoints in a cohort of patients receiving head and neck radiation with proton therapy or intensity modulated radiation therapy (IMRT). Methods: Forty patients received comprehensive head and neck radiation including bilateral cervical nodal radiation, given with or without chemotherapy, for tumors of the nasopharynx, nasal cavity or paranasal sinuses, any T stage, N0-2. Fourteen received comprehensive treatment with proton therapy, and 26 were treated with IMRT, either comprehensively or matched to proton therapy delivered to the primary tumor site. Toxicity endpoints assessed included g-tube dependence at the completion of radiation and at 3 months after radiation, opioid pain medication requirement compared to pretreatment normalized as equivalent morphine dose (EMD) at completion of treatment, and at 1 and 3 months after radiation. Results: In a multivariable model including confounding variables of concurrent chemotherapy and involved nodal disease, comprehensive head and neck radiation therapy using proton therapy was associated with a lower opioid pain requirement at the completion of radiation and a lower rate of gastrostomy tube dependence by the completion of radiation therapy and at 3 months after radiation compared to IMRT. Proton therapy was associated with statistically significant lower mean doses to the oral cavity, esophagus, larynx, and parotid glands. In subgroup analysis of 32 patients receiving concurrent chemotherapy, there was a statistically significant correlation with a greater opioid pain medication requirement at the completion of radiation and both increasing mean dose to the oral cavity and to the esophagus. Conclusions: Proton therapy was associated with significantly reduced radiation dose to assessed non-target normal tissues and a reduced rate of gastrostomy tube dependence and opioid pain medication requirements. This warrants further evaluation in larger studies, ideally with patient-reported toxicity outcomes and quality of life endpoints.
Characterization of intratumor microbiome in cancer immunotherapy
(Elsevier, 2023-07-12) Zhang, Zhao; Gao, Qian; Ren, Xiangmei; Luo, Mei; Liu, Yuan; Liu, Peilin; Liu, Yun; Ye, Youqiong; Che, Xiang; Liu, Hong; Han, Leng; Biostatistics and Health Data Science, School of Medicine
Comprehensive characterization of the transcriptional landscape in Alzheimer’s disease (AD) brains
(American Association for the Advancement of Science, 2025) Chen, Chengxuan; Zhang, Zhao; Liu, Yuan; Hong, Wei; Karahan, Hande; Wang, Jun; Li, Wenbo; Diao, Lixia; Yu, Meichen; Saykin, Andrew J.; Nho, Kwangsik; Kim, Jungsu; Han, Leng; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events. We additionally identified 25,351 aberrantly expressed ncRNAs and altered PTM events associated with AD traits and further identified the corresponding protein-coding genes to construct regulatory networks. Furthermore, we developed a user-friendly data portal, ADatlas, facilitating users in exploring our results. Our study aims to establish a comprehensive data platform for ncRNAs and PTMs in AD to advance related research.
The CYP3A5 genotypes of both liver transplant recipients and donors influence the time-dependent recovery of tacrolimus clearance during the early stage following transplantation
(Wiley, 2021-10) Huang, Li; Assiri, Abdullah A.; Wen, Peihao; Zhang, Kun; Fan, Junwei; Xing, Tonghai; Liu, Yuan; Zhang, Jinyan; Wang, Zhaowen; Su, Zhaojie; Chen, Jiajia; Xiao, Yi; Wang, Rui; Na, Risi; Yuan, Liyun; Liu, Dehua; Xia, Junjie; Zhong, Lin; Liu, Wanqing; Guo, Wenzhi; Overholser, Brian R.; Peng, Zhihai; Medicine, School of Medicine
Differences in preoperative frailty assessment of surgical candidates by sex, age, and race
(Elsevier, 2024-05-11) Nicaise, Edouard H.; Palmateer, Gregory; Schmeusser, Benjamin N.; Futral, Cameron; Liu, Yuan; Goyal, Subir; Nabavizadeh, Reza; Kooby, David A.; Maithel, Shishir K.; Sweeney, John F.; Sarmiento, Juan M.; Ogan, Kenneth; Master, Viraj A.; Urology, School of Medicine
Introduction: Surgical decision-making often relies on a surgeon's subjective assessment of a patient's frailty status to undergo surgery. Certain patient demographics can influence subjective judgment when compared to validated objective assessments. In this study, we explore the relationship between subjective and objective frailty assessments according to patient age, sex, and race. Methods: Patients were prospectively enrolled in urology, general surgery, and surgical oncology clinics. Using a visual analog scale (0-100), operating surgeons independently rated the patient's frailty status. Objective frailty was classified using the Fried Frailty Criteria ranging from 0 to 5. Multivariable proportional odds models were conducted to examine the potential association of factors with objective frailty, according to surgeon frailty rating. Subgroup analysis according to patient sex, race, and age was also performed. Results: Seven male surgeons assessed 203 patients preoperatively with a median age of 65. A majority of patients were male (61 %), white (67 %), and 60 % and 40 % underwent urologic and general surgery/surgical oncology procedures respectively. Increased subjective surgeon rating (OR 1.69; p < 0.001) was significantly associated with the presence of objective frailty. On subgroup analysis, a higher magnitude of such association was observed more in females (OR 1.86; p = 0.0007), non-white (OR 1.84; p = 0.0019), and older (>60, OR 1.75; p = 0.0001) patients, compared to male (OR 1.45; p = 0.0243), non-white (OR 1.48; p = 0.0109) and patients under 60 (OR 1.47; p = 0.0823). Conclusion: The surgeon's subjective assessment of frailty demonstrated tendencies to rate older, female, and non-white patients as frail; however, differences in patient sex, age, and race were not statistically significant.
Farnesol Delivery via Polymeric Nanoparticle Carriers Inhibits Cariogenic Cross-Kingdom Biofilms and Prevents Enamel Demineralization
(Wiley, 2022) Ito, Tatsuro; Sims, Kenneth R., Jr.; Liu, Yuan; Xiang, Zhenting; Arthur, Rodrigo A.; Hara, Anderson T.; Koo, Hyun; Benoit, Danielle S. W.; Klein, Marlise I.; Biomedical and Applied Sciences, School of Dentistry
Streptococcus mutans and Candida albicans are frequently detected together in the plaque from patients with early childhood caries (ECC) and synergistically interact to form a cariogenic cross-kingdom biofilm. However, this biofilm is difficult to control. Thus, to achieve maximal efficacy within the complex biofilm microenvironment, nanoparticle carriers have shown increased interest in treating oral biofilms in recent years. Here, we assessed the anti-biofilm efficacy of farnesol (Far), a hydrophobic antibacterial drug and repressor of Candida filamentous forms, against cross-kingdom biofilms employing drug delivery via polymeric nanoparticle carriers (NPCs). We also evaluated the effect of the strategy on teeth enamel demineralization. The farnesol-loaded NPCs (NPC+Far) resulted in a 2-log CFU/mL reduction of S. mutans and C. albicans (hydroxyapatite disc biofilm model). High-resolution confocal images further confirmed a significant reduction in exopolysaccharides, smaller microcolonies of S. mutans, and no hyphal form of C. albicans after treatment with NPC+Far on human tooth enamel (HT) slabs, altering the biofilm 3D structure. Furthermore, NPC+Far treatment was highly effective in preventing enamel demineralization on HT, reducing lesion depth (79% reduction) and mineral loss (85% reduction) versus vehicle PBS-treated HT, while NPC or Far alone had no differences with the PBS. The drug delivery via polymeric NPCs has the potential for targeting bacterial-fungal biofilms associated with a prevalent and costly pediatric oral disease, such as ECC.
Ferumoxytol Nanoparticles Target Biofilms Causing Tooth Decay in the Human Mouth
(American Chemical Society, 2021) Liu, Yuan; Huang, Yue; Kim, Dongyeop; Ren, Zhi; Oh, Min Jun; Cormode, David P.; Hara, Anderson T.; Zero, Domenick T.; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
Severe tooth decay has been associated with iron deficiency anemia that disproportionally burdens susceptible populations. Current modalities are insufficient in severe cases where pathogenic dental biofilms rapidly accumulate, requiring new antibiofilm approaches. Here, we show that ferumoxytol, a Food and Drug Administration-approved nanoparticle formulation for treating iron deficiency, exerts an alternative therapeutic activity via the catalytic activation of hydrogen peroxide, which targets bacterial pathogens in biofilms and suppresses tooth enamel decay in an intraoral human disease model. Data reveal the potent antimicrobial specificity of ferumoxytol iron oxide nanoparticles (FerIONP) against biofilms harboring Streptococcus mutans via preferential binding that promotes bacterial killing through in situ free-radical generation. Further analysis indicates that the targeting mechanism involves interactions of FerIONP with pathogen-specific glucan-binding proteins, which have a minimal effect on commensal streptococci. In addition, we demonstrate that FerIONP can detect pathogenic biofilms on natural teeth via a facile colorimetric reaction. Our findings provide clinical evidence and the theranostic potential of catalytic nanoparticles as a targeted anti-infective nanomedicine.
Flap Endonuclease 1 Endonucleolytically Processes RNA to Resolve R-Loops through DNA Base Excision Repair
(MDPI, 2022-12-29) Laverde, Eduardo E.; Polyzos, Aris A.; Tsegay, Pawlos P.; Shaver, Mohammad; Hutcheson, Joshua D.; Balakrishnan, Lata; McMurray, Cynthia T.; Liu, Yuan; Biology, School of Science
Flap endonuclease 1 (FEN1) is an essential enzyme that removes RNA primers and base lesions during DNA lagging strand maturation and long-patch base excision repair (BER). It plays a crucial role in maintaining genome stability and integrity. FEN1 is also implicated in RNA processing and biogenesis. A recent study from our group has shown that FEN1 is involved in trinucleotide repeat deletion by processing the RNA strand in R-loops through BER, further suggesting that the enzyme can modulate genome stability by facilitating the resolution of R-loops. However, it remains unknown how FEN1 can process RNA to resolve an R-loop. In this study, we examined the FEN1 cleavage activity on the RNA:DNA hybrid intermediates generated during DNA lagging strand processing and BER in R-loops. We found that both human and yeast FEN1 efficiently cleaved an RNA flap in the intermediates using its endonuclease activity. We further demonstrated that FEN1 was recruited to R-loops in normal human fibroblasts and senataxin-deficient (AOA2) fibroblasts, and its R-loop recruitment was significantly increased by oxidative DNA damage. We showed that FEN1 specifically employed its endonucleolytic cleavage activity to remove the RNA strand in an R-loop during BER. We found that FEN1 coordinated its DNA and RNA endonucleolytic cleavage activity with the 3'-5' exonuclease of APE1 to resolve the R-loop. Our results further suggest that FEN1 employed its unique tracking mechanism to endonucleolytically cleave the RNA strand in an R-loop by coordinating with other BER enzymes and cofactors during BER. Our study provides the first evidence that FEN1 endonucleolytic cleavage can result in the resolution of R-loops via the BER pathway, thereby maintaining genome integrity.
Interkingdom assemblages in human saliva display group-level surface mobility and disease-promoting emergent functions
(National Academy of Science, 2022) Ren, Zhi; Jeckel, Hannah; Simon-Soro, Aurea; Xiang, Zhenting; Liu, Yuan; Cavalcanti, Indira M.; Xiao, Jin; Tin, Nyi-Nyi; Hara, Anderson; Drescher, Knut; Koo, Hyun; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
Fungi and bacteria form multicellular biofilms causing many human infections. How such distinctive microbes act in concert spatiotemporally to coordinate disease-promoting functionality remains understudied. Using multiscale real-time microscopy and computational analysis, we investigate the dynamics of fungal and bacterial interactions in human saliva and their biofilm development on tooth surfaces. We discovered structured interkingdom assemblages displaying emergent functionalities to enhance collective surface colonization, survival, and growth. Further analyses revealed an unexpected group-level surface mobility with coordinated “leaping-like” and “walking-like” motions while continuously growing. These mobile groups of growing cells promote rapid spatial spreading of both species across surfaces, causing more extensive tooth decay. Our findings show multicellular interkingdom assemblages acting like supraorganisms with functionalities that cannot be achieved without coassembly.
PancanQTLv2.0: a comprehensive resource for expression quantitative trait loci across human cancers
(Oxford University Press, 2024) Chen, Chengxuan; Liu, Yuan; Luo, Mei; Yang, Jingwen; Chen, Yamei; Wang, Runhao; Zhou, Joseph; Zang, Yong; Diao, Lixia; Han, Leng; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
Expression quantitative trait locus (eQTL) analysis is a powerful tool used to investigate genetic variations in complex diseases, including cancer. We previously developed a comprehensive database, PancanQTL, to characterize cancer eQTLs using The Cancer Genome Atlas (TCGA) dataset, and linked eQTLs with patient survival and GWAS risk variants. Here, we present an updated version, PancanQTLv2.0 (https://hanlaboratory.com/PancanQTLv2/), with advancements in fine-mapping causal variants for eQTLs, updating eQTLs overlapping with GWAS linkage disequilibrium regions and identifying eQTLs associated with drug response and immune infiltration. Through fine-mapping analysis, we identified 58 747 fine-mapped eQTLs credible sets, providing mechanic insights of gene regulation in cancer. We further integrated the latest GWAS Catalog and identified a total of 84 592 135 linkage associations between eQTLs and the existing GWAS loci, which represents a remarkable ∼50-fold increase compared to the previous version. Additionally, PancanQTLv2.0 uncovered 659516 associations between eQTLs and drug response and identified 146948 associations between eQTLs and immune cell abundance, providing potentially clinical utility of eQTLs in cancer therapy. PancanQTLv2.0 expanded the resources available for investigating gene expression regulation in human cancers, leading to advancements in cancer research and precision oncology.

Browsing by Author "Liu, Yuan"

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