Biomedical Informatics Commons^™

Effect Of Esketamine On Hypotension In Women With Preoperative Anxiety Undergoing Elective Cesarean Section: A Randomized, Double-Blind, Controlled Trial, Yu Qi, Meiyan Zhou, Yaqi Dong, Wenting Zheng, Qinyu Jiang, Yanyu Li, Xinghe Wang, Jia Sun, Hai Zhou, Zhengquan Hu, Liwei Wang

Faculty, Staff and Student Publications

To investigate the effect of low-doses esketamine on spinal anesthesia-induced hypotension in women with preoperative anxiety undergoing elective cesarean section, the randomized controlled trial enrolled 120 women aged 18-35 years who preoperative State-Trait Anxiety Inventory State scores > 40, conducted from September 2022 to August 2023 in Xuzhou Central Hospital, China. Women in the esketamine group received a single intravenous injection of 0.2 mg/kg esketamine after sensory block level achieved. The incidence of hypotension in the esketamine group was significantly lower than the control group at T2 (10% [6 of 60]; P < 0.001), T3 (5.0% [3 of 60]; P = 0.007) and T4(5.0% [3 of 60]; P = 0.004). Despite being higher in the esketamine group, the overall rates of hypertension (11.7% [7 of 60]; P = 0.186), tachycardia (23.3% [14 of 60]; P = 0.246), and bradycardia (0.0% [0 of 60]; P = 0.079) were no significantly difference between the two groups. STAI-S scores was significantly lower in the esketamine group (mean [SD] 37.52[7.14]) than in the control group (mean [SD] 41.03[9.66], P = 0.39) in postoperative day 1. Spinal anesthesia combined with intravenous low-doses esketamine infusion can significantly reduce the incidence of hypotension in women with preoperative anxiety undergoing elective cesarean section.

Differential Lipid Binding Specificities Of Rap1a And Rap1b Are Encoded By The Amino Acid Sequence Of The Membrane Anchors, Mussie K Araya, Wei Chen, Yuepeng Ke, Yubin Zhou, Alemayehu A Gorfe, John F Hancock, Junchen Liu

Faculty, Staff and Student Publications

RAP1 proteins belong to the RAS family of small GTPases that operate as molecular switches by cycling between GDP-bound inactive and GTP-bound active states. The C-terminal anchors of RAP1 proteins are known to direct membrane localization, but how these anchors organize RAP1 on the plasma membrane (PM) has not been investigated. Using high-resolution imaging, we show that RAP1A and RAP1B form spatially segregated nanoclusters on the inner leaflet of the PM, with further lateral segregation between GDP-bound and GTP-bound proteins. The C-terminal polybasic anchors of RAP1A and RAP1B differ in their amino acid sequences and exhibit different lipid binding specificities, …

Multi-Antigen Intranasal Vaccine Protects Against Challenge With Sarbecoviruses And Prevents Transmission In Hamsters, Ankita Leekha, Arash Saeedi, K M Samiur Rahman Sefat, Monish Kumar, Melisa Martinez-Paniagua, Adrian Damian, Rohan Kulkarni, Kate Reichel, Ali Rezvan, Shalaleh Masoumi, Xinli Liu, Laurence J N Cooper, Manu Sebastian, Courtney M Sands, Vallabh E Das, Nimesh B Patel, Brett Hurst, Navin Varadarajan

Faculty, Staff and Student Publications

Immunization programs against SARS-CoV-2 with commercial intramuscular vaccines prevent disease but are less efficient in preventing infections. Mucosal vaccines can provide improved protection against transmission, ideally for different variants of concern (VOCs) and related sarbecoviruses. Here, we report a multi-antigen, intranasal vaccine, NanoSTING-SN (NanoSTING-Spike-Nucleocapsid), eliminates virus replication in both the lungs and the nostrils upon challenge with the pathogenic SARS-CoV-2 Delta VOC. We further demonstrate that NanoSTING-SN prevents transmission of the SARS-CoV-2 Omicron VOC (BA.5) to vaccine-naïve hamsters. To evaluate protection against other sarbecoviruses, we immunized mice with NanoSTING-SN. We showed that immunization affords protection against SARS-CoV, leading to protection …

Cell-Specific Regulation Of The Circadian Clock By Bmal1 In The Paraventricular Nucleus: Implications For Regulation Of Systemic Biological Rhythms, Rachel Van Drunen, Yulin Dai, Haichao Wei, Baharan Fekry, Sina Noori, Samay Shivshankar, Rafael Bravo, Zhongming Zhao, Seung-Hee Yoo, Nicholas Justice, Jia Qian Wu, Qingchun Tong, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Circadian rhythms are internal biological rhythms driving temporal tissue-specific, metabolic programs. Loss of the circadian transcription factor BMAL1 in the paraventricular nucleus (PVN) of the hypothalamus reveals its importance in metabolic rhythms, but its functions in individual PVN cells are poorly understood. Here, loss of BMAL1 in the PVN results in arrhythmicity of processes controlling energy balance and alters peripheral diurnal gene expression. BMAL1 chromatin immunoprecipitation sequencing (ChIP-seq) and single-nucleus RNA sequencing (snRNA-seq) reveal its temporal regulation of target genes, including oxytocin (OXT), and restoring circulating OXT peaks in BMAL1-PVN knockout (KO) mice rescues absent activity rhythms. While glutamatergic neurons …

Impact Of Patient Demographics And Neighborhood Socioeconomic Variables On Clinical Trial Participation Patterns For Nhl, Chijioke Nze, Clark R Andersen, Amy A Ayers, Jason Westin, Michael Wang, Swaminathan Iyer, Sairah Ahmed, Chelsea Pinnix, Francisco Vega, Lynne Nguyen, Lorna Mcneill, Loretta J Nastoupil, Kehe Zhang, Cici X Bauer, Christopher R Flowers

Faculty, Staff and Student Publications

Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective analysis of patients with non-Hodgkin lymphoma (NHL) seen at MD Anderson Cancer Center (MDACC) to investigate the association between trial participation, race/ethnicity, travel distance, and neighborhood socioeconomic status (nSES). Using patient addresses, we ascertained nSES variables on educational attainment, income, poverty, racial composition, and housing at the census tract (CT) level. We also performed geospatial analysis to determine the geographic distribution of clinical trial participants and distance from patient residence to MDACC. We examined 3146 consecutive …

A Scaled Proteomic Discovery Study For Prostate Cancer Diagnostic Markers Using Proteograph, Matthew E K Chang, Jane Lange, Jessie May Cartier, Travis W Moore, Sophia M Soriano, Brenna Albracht, Michael Krawitzky, Harendra Guturu, Amir Alavi, Alexey Stukalov, Xiaoyuan Zhou, Eltaher M Elgierari, Jessica Chu, Ryan Benz, Juan C Cuevas, Shadi Ferdosi, Daniel Hornburg, Omid Farokhzad, Asim Siddiqui, Serafim Batzoglou, Robin J Leach, Michael A Liss, Ryan P Kopp, Mark R Flory

Faculty, Staff and Student Publications

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate …

Sart3 Reads Methylarginine-Marked Glycine- And Arginine-Rich Motifs, Yalong Wang, Jujun Zhou, Wei He, Rongjie Fu, Leilei Shi, Ngoc Khoi Dang, Bin Liu, Han Xu, Xiaodong Cheng, Mark T Bedford

Faculty, Staff and Student Publications

Glycine- and arginine-rich (GAR) motifs, commonly found in RNA-binding and -processing proteins, can be symmetrically (SDMA) or asymmetrically (ADMA) dimethylated at the arginine residue by protein arginine methyltransferases. Arginine-methylated protein motifs are usually read by Tudor domain-containing proteins. Here, using a GFP-Trap, we identify a non-Tudor domain protein, squamous cell carcinoma antigen recognized by T cells 3 (SART3), as a reader for SDMA-marked GAR motifs. Structural analysis and mutagenesis of SART3 show that aromatic residues lining a groove between two adjacent aromatic-rich half-a-tetratricopeptide (HAT) repeat domains are essential for SART3 to recognize and bind to SDMA-marked GAR motif peptides, as …

First-In-Human Dose Escalation Trial To Evaluate The Clinical Safety And Efficacy Of An Anti-Magea1 Autologous Tcr-Transgenic T Cell Therapy In Relapsed And Refractory Solid Tumors, Martin Wermke, Tobias A W Holderried, Jason John Luke, Van K Morris, Winfried H Alsdorf, Katrin Wetzko, Borje S Andersson, Ignacio I Wistuba, Edwin R Parra, Mohammad B Hossain, Sandra Grund-Gröschke, Katrin Aslan, Arun Satelli, Anantha Marisetty, Swapna Satam, Mamta Kalra, Jens Hukelmann, M Alper Kursunel, Karine Pozo, Andreas Acs, Linus Backert, Melissa Baumeister, Sebastian Bunk, Claudia Wagner, Oliver Schoor, Ali S Mohamed, Andrea Mayer-Mokler, Norbert Hilf, Delfi Krishna, Steffen Walter, Apostolia M Tsimberidou, Cedrik M Britten

Faculty, Staff and Student Publications

RATIONALE OF THE TRIAL: Although the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid tumors is still challenging. We investigated the safety and tolerability of IMA202 in a first-in-human, dose escalation basket trial in human leucocyte antigen A*02:01 positive patients with melanoma-associated antigen A1 (MAGEA1)-positive advanced solid tumors.

TRIAL DESIGN: The 2+2 trial design was an algorithmic design based on a maximally acceptable dose-limiting toxicity (DLT) rate of 25% and the sample size was driven by the algorithmic design with a maximum of …

Radium-223 Treatment Produces Prolonged Suppression Of Resident Osteoblasts And Decreased Bone Mineral Density In Trabecular Bone In Osteoblast Reporter Mice, Song-Chang Lin, Guoyu Yu, Paul G Corn, Jossana Damasco, Yu-Chen Lee, Jian H Song, Nora M Navone, Christopher J Logothetis, Marites P Melancon, Theocharis Panaretakis, Sue-Hwa Lin

Faculty, Staff and Student Publications

Radium 223 (Ra-223) is an α-emitting bone-homing radiopharmaceutical that targets tumor-induced osteoblasts and is used to reduce bone pain and prolong overall survival in men with bone-metastatic, castrate-resistant prostate cancer. However, increased fracture risk in skeletal sites with no bone metastasis has been observed in patients treated with Ra-223. Both luciferase- or green fluorescence protein (GFP)-labeled osteoblast reporter mice were used to monitor the effect of Ra-223 on resident osteoblasts and normal bone structure. Upon Ra-223 treatment, 70% of resident osteoblasts were reduced within 2 days, and the osteoblast reduction lasted for at least 18 weeks without detectable recovery, as …

Low Skeletal Muscle Mass Is Associated With Inferior Preoperative And Postoperative Shoulder Function In Elderly Rotator Cuff Tear Patients, Yang Yang, Binbin Zheng, Xiaofang Lin, Mengqin Zhang, Yongzhi Ye, Haixiao Chen, Xiaobo Zhou

Faculty, Staff and Student Publications

BACKGROUND: The age-related loss of skeletal muscle mass is an important characteristic of sarcopenia, an increasingly recognized condition with systemic implications. However, its association with shoulder function in elderly patients with rotator cuff tears (RCT) remains unknown. This study aimed to investigate the relationship between low skeletal muscle mass and shoulder function in elderly RCT patients.

METHODS: A retrospective analysis was conducted on RCT patients who underwent chest computed tomography (CT) scans for clinical evaluation. Preoperative CT scan images of the chest were used to calculate the cross-sectional area (CSA) of thoracic muscle at the T4 level. The medical records …

Safety And Effectiveness Of Using Disposable Ultrasonic Shears To Coagulate 5–7 Mm Blood Vessels: Protocol For A Prospective, Multicenter, Randomized, Parallel Controlled, Non-Inferiority Clinical Trial, Xipeng Wang, Chengqiang Li, Junqiang Fan, Jian Hu, Mingsong Wang, Hecheng Li

Faculty, Staff and Student Publications

BACKGROUND: The ultrasonic scalpel is widely used during surgery. It is safe and effective to close the pulmonary artery branch vessels of 7 mm or below with an ultrasonic energy device as reported. However, there have been no multicenter randomized clinical trial to assess the safety and effectiveness of using ultrasonic scalpel to coagulate 5-7 mm blood vessels in thoracic surgery.

METHODS: This is a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial. A total of 144 eligible patients planning to undergo lung or esophageal surgery will be randomly allocated to the experimental group and the control group. The investigational …

Bayesian Sequential Monitoring Strategies For Trials Of Digestive Cancer Therapeutics, Guillaume Mulier, Ruitao Lin, Thomas Aparicio, Lucie Biard

Faculty, Staff and Student Publications

Background: New therapeutics in oncology have presented challenges to existing paradigms and trial designs in all phases of drug development. As a motivating example, we considered an ongoing phase II trial planned to evaluate the combination of a MET inhibitor and an anti-PD-L1 immunotherapy to treat advanced oesogastric carcinoma. The objective of the paper was to exemplify the planning of an adaptive phase II trial with novel anti-cancer agents, including prolonged observation windows and joint sequential evaluation of efficacy and toxicity.

Methods: We considered various candidate designs and computed decision rules assuming correlations between efficacy and toxicity. Simulations were conducted …

Exploration Of A Potential Door Endpoint For Hospital-Acquired Bacterial Pneumonia And Ventilator-Associated Bacterial Pneumonia Using Six Registrational Trials For Antibacterial Drugs, Tori Kinamon, Ursula Waack, Mark Needles, Daniel Rubin, Deborah Collyar, Sarah B Doernberg, Scott R Evans, Toshimitsu Hamasaki, Thomas L Holland, Jessica Howard-Anderson, Henry Chambers, Vance G Fowler, Sumati Nambiar, Peter Kim, Helen W Boucher, Ramya Gopinath

Faculty, Staff and Student Publications

BACKGROUND: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

METHODS: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that …

Membrane Vectorial Lipidomic Features Of Coral Host Cells’ Plasma Membrane And Lipid Profiles Of Their Endosymbionts Cladocopium, Tatyana V Sikorskaya, Ekaterina V Ermolenko, Taliya T Ginanova, Andrey V Boroda, Kseniya V Efimova, Mikhail Bogdanov

Faculty, Staff and Student Publications

The symbiotic relationships between coral animal host and autotrophic dinoflagellates are based on the mutual exchange and tight control of nutritional inputs supporting successful growth. The corals Sinularia heterospiculata and Acropora aspera were cultivated using a flow-through circulation system supplying seawater during cold and warm seasons of the year, then sorted into host cells and symbionts and subjected to phylogenetic, morphological, and advanced lipid analyses. Here we show, that the lipidomes of the dinoflagellates Cladocopium C1/C3 and acroporide-specific Cladocopium hosted by the corals, are determined by lipidomic features of different thermosensitivity and unique betaine- and phospholipid molecular species. Phosphatidylserines and …

Prediction Of Mild Cognitive Impairment Status: Pilot Study Of Machine Learning Models Based On Longitudinal Data From Fitness Trackers, Qidi Xu, Yejin Kim, Karen Chung, Paul Schulz, Assaf Gottlieb

Faculty, Staff and Student Publications

BACKGROUND: Early signs of Alzheimer disease (AD) are difficult to detect, causing diagnoses to be significantly delayed to time points when brain damage has already occurred and current experimental treatments have little effect on slowing disease progression. Tracking cognitive decline at early stages is critical for patients to make lifestyle changes and consider new and experimental therapies. Frequently studied biomarkers are invasive and costly and are limited for predicting conversion from normal to mild cognitive impairment (MCI).

OBJECTIVE: This study aimed to use data collected from fitness trackers to predict MCI status.

METHODS: In this pilot study, fitness trackers were …

Targeted Sequencing For Hereditary Breast And Ovarian Cancer In Brca1/2-Negative Families Reveals Complex Genetic Architecture And Phenocopies, Jocelyn N Plowman, Evanjalina J Matoy, Lavanya V Uppala, Samantha B Draves, Cynthia J Watson, Bridget A Sefranek, Mark L Stacey, Samuel P Anderson, Michael A Belshan, Elizabeth E Blue, Chad D Huff, Yusi Fu, Holly A F Stessman

Faculty, Staff and Student Publications

Approximately 20% of breast cancer cases are attributed to increased family risk, yet variation in BRCA1/2 can only explain 20%-25% of cases. Historically, only single gene or single variant testing were common in at-risk family members, and further sequencing studies were rarely offered after negative results. In this study, we applied an efficient and inexpensive targeted sequencing approach to provide molecular diagnoses in 245 human samples representing 134 BRCA mutation-negative (BRCAX) hereditary breast and ovarian cancer (HBOC) families recruited from 1973 to 2019 by Dr. Henry Lynch. Sequencing identified 391 variants, which were functionally annotated and ranked based on their …

In Vitro Data Suggest A Role For Pms2 Kozak Sequence Mutations In Lynch Syndrome Risk, Evanjalina J Matoy, Jocelyn N Plowman, Cynthia J Watson, Michael A Belshan, Elizabeth E Blue, Chad D Huff, Holly A F Stessman

Faculty, Staff and Student Publications

This study investigates the role of 5′ UTR PMS2 Kozak sequence genetic variation in cancer risk. It accomplishes this through the development of a mid-throughput reporter assay where variants can be tested for protein translation efficiency. The results highlight the importance of continued study of the Kozak sequence related to human disease.

Deepface: Deep-Learning-Based Framework To Contextualize Orofacial-Cleft-Related Variants During Human Embryonic Craniofacial Development, Yulin Dai, Toshiyuki Itai, Guangsheng Pei, Fangfang Yan, Yan Chu, Xiaoqian Jiang, Seth M Weinberg, Nandita Mukhopadhyay, Mary L Marazita, Lukas M Simon, Peilin Jia, Zhongming Zhao

Faculty, Staff and Student Publications

Orofacial clefts (OFCs) are among the most common human congenital birth defects. Previous multiethnic studies have identified dozens of associated loci for both cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP). Although several nearby genes have been highlighted, the "casual" variants are largely unknown. Here, we developed DeepFace, a convolutional neural network model, to assess the functional impact of variants by SNP activity difference (SAD) scores. The DeepFace model is trained with 204 epigenomic assays from crucial human embryonic craniofacial developmental stages of post-conception week (pcw) 4 to pcw 10. The Pearson correlation coefficient between …

Investigating Gene Functions And Single-Cell Expression Profiles Of De Novo Variants In Orofacial Clefts, Toshiyuki Itai, Fangfang Yan, Andi Liu, Yulin Dai, Chihiro Iwaya, Sarah W Curtis, Elizabeth J Leslie, Lukas M Simon, Peilin Jia, Xiangning Chen, Junichi Iwata, Zhongming Zhao

Faculty, Staff and Student Publications

Orofacial clefts (OFCs) are common congenital birth defects with various etiologies, including genetic variants. Online Mendelian Inheritance in Man (OMIM) annotated several hundred genes involving OFCs. Furthermore, several hundreds of de novo variants (DNVs) have been identified from individuals with OFCs. Some DNVs are related to known OFC genes or pathways, but there are still many DNVs whose relevance to OFC development is unknown. To explore novel gene functions and their cellular expression profiles, we focused on DNVs in genes that were not listed in OMIM. We collected 960 DNVs in 853 genes from published studies and curated these genes, …

Crispr-Cas9 And Cas12a Target Site Richness Reflects Genomic Diversity In Natural Populations Of Anopheles Gambiae And Aedes Aegypti Mosquitoes, Travis C Collier, Yoosook Lee, Derrick K Mathias, Víctor López Del Amo

Faculty, Staff and Student Publications

Due to limitations in conventional disease vector control strategies including the rise of insecticide resistance in natural populations of mosquitoes, genetic control strategies using CRISPR gene drive systems have been under serious consideration. The identification of CRISPR target sites in mosquito populations is a key aspect for developing efficient genetic vector control strategies. While genome-wide Cas9 target sites have been explored in mosquitoes, a precise evaluation of target sites focused on coding sequence (CDS) is lacking. Additionally, target site polymorphisms have not been characterized for other nucleases such as Cas12a, which require a different DNA recognition site (PAM) and would …

Epigenome-Wide Association Study Of Lung Cancer Among Never Smokers In Two Prospective Cohorts In Shanghai, China, Mohammad L Rahman, Charles E Breeze, Xiao-Ou Shu, Jason Y Y Wong, Batel Blechter, Andres Cardenas, Xuting Wang, Bu-Tian Ji, Wei Hu, Qiuyin Cai, H Dean Hosgood, Gong Yang, Jianxin Shi, Jirong Long, Yu-Tang Gao, Douglas A Bell, Wei Zheng, Nathaniel Rothman, Qing Lan

Faculty, Staff and Student Publications

BACKGROUND: The aetiology of lung cancer among individuals who never smoked remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Epigenetic alterations, particularly DNA methylation (DNAm) changes, have emerged as potential drivers. Yet, few prospective epigenome-wide association studies (EWAS), primarily focusing on peripheral blood DNAm with limited representation of never smokers, have been conducted.

METHODS: We conducted a nested case-control study of 80 never-smoking incident lung cancer cases and 83 never-smoking controls within the Shanghai Women's Health Study and Shanghai Men's Health Study. DNAm was measured in prediagnostic oral rinse …

Hiv/Aids-Associated Knowledge And Attitudes Towards Treating Disadvantaged Communities Among Pre-Community-Based Dental Education Dental Students In The Us, Aditi Tomar, Hannah Balcezak, Shirley Lewis Miranda, Marie C Latortue, Richa Chinchkhandi, Lisa Wigfall

Faculty, Staff and Student Publications

This study examines HIV/AIDS-associated knowledge and attitudes towards treating disadvantaged communities among predoctoral dental students in U.S. dental schools who have not yet commenced their Community-Based Dental Education (CBDE) training. It also compares the difference in the knowledge and attitudes between students with reported community engagement with PLWHA and those without. Our study comprised 89 predoctoral dental students within their D1-D3 years of dental school who had not yet initiated their Community-Based Dental Education (referred to as pre-CBDE dental students). Their responses were collected via an online survey. The participants were 68% females, 94% heterosexual, and with a mean age …

Extracellular Vesicles, Circadian Rhythms, And Cancer: A Comprehensive Review With Emphasis On Hepatocellular Carcinoma, Baharan Fekry, Lierni Ugartemendia, Nestor F Esnaola, Laura Goetzl

Faculty, Staff and Student Publications

This review comprehensively explores the complex interplay between extracellular vesicles (ECVs)/exosomes and circadian rhythms, with a focus on the role of this interaction in hepatocellular carcinoma (HCC). Exosomes are nanovesicles derived from cells that facilitate intercellular communication by transporting bioactive molecules such as proteins, lipids, and RNA/DNA species. ECVs are implicated in a range of diseases, where they play crucial roles in signaling between cells and their surrounding environment. In the setting of cancer, ECVs are known to influence cancer initiation and progression. The scope of this review extends to all cancer types, synthesizing existing knowledge on the various roles …

Enhancing The Carbon Monoxide Oxidation Performance Through Surface Defect Enrichment Of Ceria-Based Supports For Platinum Catalyst, Shaohua Xie, Yue Lu, Kailong Ye, Wei Tan, Sufeng Cao, Chunying Wang, Daekun Kim, Xing Zhang, Jeremia Loukusa, Yaobin Li, Yan Zhang, Lu Ma, Steven N Ehrlich, Nebojsa S Marinkovic, Jiguang Deng, Maria Flytzani-Stephanopoulos, Fudong Liu

Faculty, Staff and Student Publications

Effective synthesis and application of single-atom catalysts on supports lacking enough defects remain a significant challenge in environmental catalysis. Herein, we present a universal defect-enrichment strategy to increase the surface defects of CeO2-based supports through H2 reduction pretreatment. The Pt catalysts supported by defective CeO2-based supports, including CeO2, CeZrOx, and CeO2/Al2O3 (CA), exhibit much higher Pt dispersion and CO oxidation activity upon reduction activation compared to their counterpart catalysts without defect enrichment. Specifically, Pt is present as embedded single atoms on the CA support with enriched surface defects (CA-HD) based on which the highly active catalyst showing embedded …

Biophysics Of Protein-Lipid Interactions, Paula A Bender, Vasanthi Jayaraman

Faculty, Staff and Student Publications

The biological phenomenon of protein-lipid interactions in cell membranes underlies the diversity of peripheral membrane protein function and physical properties of the membrane. To summarize novel findings in the field, this research highlight focuses on recent publications in Biophysical Journal.

Antitumor Activity Of A Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting Lgr5 In Preclinical Models Of Neuroblastoma, Jianghua Tu, Yukimatsu Toh, Adela M Aldana, Jake J Wen, Ling Wu, Joan Jacob, Li Li, Sheng Pan, Kendra S Carmon, Qingyun J Liu

Faculty, Staff and Student Publications

Neuroblastoma (NB) is a cancer of the peripheral nervous system found in children under 15 years of age. It is the most frequently diagnosed cancer during infancy, accounting for ~12% of all cancer-related deaths in children. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a membrane receptor that is associated with the primary tumor formation and metastasis of cancers in the gastrointestinal system. Remarkably, high levels of LGR5 are found in NB tumor cells, and high LGR5 expression is strongly correlated with poor survival. Antibody-drug conjugates (ADCs) are monoclonal antibodies that are covalently linked to cell-killing cytotoxins to deliver the payloads …

Trps1 Expression Is Frequently Seen In A Subset Of Cutaneous Mesenchymal Neoplasms And Tumors Of Uncertain Differentiation: A Potential Diagnostic Pitfall, Moon Joo Kim, Yi A Liu, Yunyi Wang, Jing Ning, Woo Cheal Cho

Faculty, Staff and Student Publications

Although extensively studied in cutaneous epithelial neoplasms, the TRPS1 immunoreactivity in cutaneous mesenchymal neoplasms and tumors of uncertain differentiation (CMNTUDs), such as atypical fibroxanthoma (AFX), remains largely unexplored. We assessed TRPS1 immunoreactivity in 135 CMNTUDs, comprising 46 fibrohistiocytic/fibroblastic tumors, 28 vascular tumors, 24 peripheral nerve sheath tumors (PNSTs), 21 tumors of uncertain differentiation, and 16 smooth muscle tumors. Additionally, we included selected cases of melanoma with spindled cell morphology or desmoplastic features (n = 9) and sarcomatoid squamous cell carcinoma (SSCC) (n = 5) to compare TRPS1 expression patterns with those of AFX. TRPS1 expression was prevalent in dermatofibromas (24/24), …

Nrg Oncology And Particle Therapy Co-Operative Group Patterns Of Practice Survey And Consensus Recommendations On Pencil-Beam Scanning Proton Stereotactic Body Radiation Therapy And Hypofractionated Radiation Therapy For Thoracic Malignancies, Wei Liu, Hongying Feng, Paige A Taylor, Minglei Kang, Jiajian Shen, Jatinder Saini, Jun Zhou, Huan B Giap, Nathan Y Yu, Terence S Sio, Pranshu Mohindra, Joe Y Chang, Jeffrey D Bradley, Ying Xiao, Charles B Simone, Liyong Lin

Faculty, Staff and Student Publications

Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally fractionated PBSPT because of concerns of amplified uncertainties at the larger dose per fraction. The NRG Oncology and Particle Therapy Cooperative Group Thoracic Subcommittee surveyed proton centers in …

Clinical And Genomic Landscape Of Ras Mutations In Gynecologic Cancers, Ji Son, Yingao Zhang, Heather Lin, Oriol Mirallas, Pablo Alvarez Ballesteros, Mirella Nardo, Natalie Clark, R Tyler Hillman, Erick Campbell, Vijaykumar Holla, Amber M Johnson, Amadeo B Biter, Ying Yuan, Lauren P Cobb, David M Gershenson, Amir A Jazaeri, Karen H Lu, Pamela T Soliman, Shannon N Westin, Elizabeth D Euscher, Barrett C Lawson, Richard K Yang, Funda Meric-Bernstam, David S Hong

Faculty, Staff and Student Publications

Purpose: We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.

Experimental design: Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by the Kaplan-Meier method, and multivariable analysis was performed using the Cox proportional hazard model.

Results: Of 3,328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs. 60 years nonmutated), had a higher prevalence of endometriosis (27.3% vs. 16.9%), and …

Single-Cell Total-Rna Profiling Unveils Regulatory Hubs Of Transcription Factors, Yichi Niu, Jiayi Luo, Chenghang Zong

Faculty, Staff and Students Publications

Recent development of RNA velocity uses master equations to establish the kinetics of the life cycle of RNAs from unspliced RNA to spliced RNA (i.e., mature RNA) to degradation. To feed this kinetic analysis, simultaneous measurement of unspliced RNA and spliced RNA in single cells is greatly desired. However, the majority of single-cell RNA-seq chemistry primarily captures mature RNA species to measure gene expressions. Here, we develop a one-step total-RNA chemistry-based single-cell RNA-seq method: snapTotal-seq. We benchmark this method with multiple single-cell RNA-seq assays in their performance in kinetic analysis of cell cycle by RNA velocity. Next, with LASSO regression …