Digital Commons Network^™

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

An Evolutionarily Nascent Architecture Underlying The Formation And Emergence Of Biomolecular Condensates, Nima Jaberi-Lashkari, Byron Lee, Fardin Aryan, Eliezer Calo

Faculty, Staff and Student Publications

Biomolecular condensates are implicated in core cellular processes such as gene regulation and ribosome biogenesis. Although the architecture of biomolecular condensates is thought to rely on collective interactions between many components, it is unclear how the collective interactions required for their formation emerge during evolution. Here, we show that the structure and evolution of a recently emerged biomolecular condensate, the nucleolar fibrillar center (FC), is explained by a single self-assembling scaffold, TCOF1. TCOF1 is necessary to form the FC, and it structurally defines the FC through self-assembly mediated by homotypic interactions of serine/glutamate-rich low-complexity regions (LCRs). Finally, introduction of TCOF1 …

Mapping The Evolution Of T Cell States During Response And Resistance To Adoptive Cellular Therapy, Pavan Bachireddy, Elham Azizi, Cassandra Burdziak, Vinhkhang N Nguyen, Christina S Ennis, Katie Maurer, Cameron Y Park, Zi-Ning Choo, Shuqiang Li, Satyen H Gohil, Neil G Ruthen, Zhongqi Ge, Derin B Keskin, Nicoletta Cieri, Kenneth J Livak, Haesook T Kim, Donna S Neuberg, Robert J Soiffer, Jerome Ritz, Edwin P Alyea, Dana Pe'er, Catherine J Wu

Faculty, Staff and Student Publications

No abstract provided.

Bcl-2 Inhibition Combined With Pparα Activation Synergistically Targets Leukemic Stem Cell-Like Cells In Acute Myeloid Leukemia, Chendi Xie, Hui Zhou, Dongmei Qin, Huijian Zheng, Yuanfang Tang, Wenjuan Li, Jie Zhou, Long Liu, Xinxin Yu, Hongpeng Duan, Yong Zhou, Zhifeng Li, Zhihong Fang, Yiming Luo, Bing Z Carter, Bing Xu, Jie Zha

Faculty, Staff and Student Publications

Persistence of leukemic stem cells (LSCs) is one of the determining factors to acute myeloid leukemia (AML) treatment failure and responsible for the poor prognosis of the disease. Hence, novel therapeutic strategies that target LSCs are crucial for treatment success. We investigated if targeting Bcl-2 and peroxisome proliferator activated receptor α (PPARα), two distinct cell survival regulating mechanisms could eliminate LSCs. This study demonstrate that the Bcl-2 inhibitor venetoclax combined with the PPARα agonist chiglitazar resulted in synergistic killing of LSC-like cell lines and CD34+ primary AML cells while sparing their normal counterparts. Furthermore, the combination regimen significantly suppressed AML …

Lanthanide-Mofs As Multi-Responsive Photoluminescence Sensor For Sensitively Detecting Fe3+, Cr2o72− And Nitrofuran Antibiotics, Jingjuan Feng, Cunding Kong, Yunhui Chen, Peipei Cen, Yi Ding, Yan Guo, Fengyuan Zhang, Xiangyu Liu

Faculty, Staff and Student Publications

Fast and selective detection of contaminants plays a key role in meeting human health and environmental concerns. Herein, two groups of isostructural lanthanide MOFs, [Ln(Hpta)(oxalic acid)]·H

Hypothyroidism Following Radiotherapy For Head And Neck Cancer: A Systematic Review Of The Literature And Opportunities To Improve The Therapeutic Ratio, Michael K Rooney, Lauren M Andring, Kelsey L Corrigan, Vincent Bernard, Tyler D Williamson, Clifton D Fuller, Adam S Garden, Brandon Gunn, Anna Lee, Amy C Moreno, William H Morrison, Jack Phan, David I Rosenthal, Michael Spiotto, Steven J Frank

Faculty, Staff and Student Publications

(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and …

Early Treatment With Vigabatrin Does Not Decrease Focal Seizures Or Improve Cognition In Tuberous Sclerosis Complex: The Prevent Trial, Elizabeth Martina Bebin, Jurriaan M Peters, Brenda E Porter, Tarrant O Mcpherson, Sarah O'Kelley, Mustafa Sahin, Katherine S Taub, Rajsekar Rajaraman, Stephanie C Randle, William M Mcclintock, Mary Kay Koenig, Mike D Frost, Hope A Northrup, Klaus Werner, Danielle A Nolan, Michael Wong, Jessica L Krefting, Fred Biasini, Kalyani Peri, Gary Cutter, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.

Results: Of 84 infants enrolled, 12 were screen failures, 4 went straight to …

Early Treatment With Vigabatrin Does Not Decrease Focal Seizures Or Improve Cognition In Tuberous Sclerosis Complex: The Prevent Trial, Elizabeth Martina Bebin, Jurriaan M Peters, Brenda E Porter, Tarrant O Mcpherson, Sarah O'Kelley, Mustafa Sahin, Katherine S Taub, Rajsekar Rajaraman, Stephanie C Randle, William M Mcclintock, Mary Kay Koenig, Mike D Frost, Hope A Northrup, Klaus Werner, Danielle A Nolan, Michael Wong, Jessica L Krefting, Fred Biasini, Kalyani Peri, Gary Cutter, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: This study was undertaken to test the hypothesis that early vigabatrin treatment in tuberous sclerosis complex (TSC) infants improves neurocognitive outcome at 24 months of age.

Methods: A phase IIb multicenter randomized double-blind placebo-controlled trial was conducted of vigabatrin at first epileptiform electroencephalogram (EEG) versus vigabatrin at seizure onset in infants with TSC. Primary outcome was Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive assessment score at 24 months. Secondary outcomes were prevalence of drug-resistant epilepsy, additional developmental outcomes, and safety of vigabatrin.

Results: Of 84 infants enrolled, 12 were screen failures, 4 went straight to …

Non-Coding Rnas: Foes Or Friends For Targeting Tumor Microenvironment, Anna Szymanowska, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Paola Amero

Faculty, Staff and Student Publications

Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the field. The advancement of this technique has broadened our understanding of the molecular biology of cancer, presenting abundant possibilities for the exploration of novel biomarkers for cancer treatment. In this review, we will summarize recent achievements in understanding the complex role of ncRNA in the tumor microenvironment, we will report the latest studies on the tumor microenvironment …

Are We Focused On The Wrong Early Postoperative Quality Metrics? Optimal Realignment Outweighs Perioperative Risk In Adult Spinal Deformity Surgery, Peter G Passias, Tyler K Williamson, Jamshaid M Mir, Justin S Smith, Virginie Lafage, Renaud Lafage, Breton Line, Alan H Daniels, Jeffrey L Gum, Andrew J Schoenfeld, David Kojo Hamilton, Alex Soroceanu, Justin K Scheer, Robert Eastlack, Gregory M Mundis, Bassel Diebo, Khaled M Kebaish, Richard A Hostin, Munish C Gupta, Han Jo Kim, Eric O Klineberg, Christopher P Ames, Robert A Hart, Douglas C Burton, Frank J Schwab, Christopher I Shaffrey, Shay Bess, International Spine Study Group

Faculty, Staff and Student Publications

BACKGROUND: While reimbursement is centered on 90-day outcomes, many patients may still achieve optimal, long-term outcomes following adult spinal deformity (ASD) surgery despite transient short-term complications.

OBJECTIVE: Compare long-term clinical success and cost-utility between patients achieving optimal realignment and suboptimally aligned peers.

STUDY DESIGN/SETTING: Retrospective cohort study of a prospectively collected multicenter database.

METHODS: ASD patients with two-year (2Y) data included. Groups were propensity score matched (PSM) for age, frailty, body mass index (BMI), Charlson Comorbidity Index (CCI), and baseline deformity. Optimal radiographic criteria are defined as meeting low deformity in all three (Scoliosis Research Society) SRS-Schwab parameters or being …

The Histone Chaperone Function Of Daxx Is Dispensable For Embryonic Development, Chang Sun, Yuan Qi, Natalie Fowlkes, Nina Lazic, Xiaoping Su, Guillermina Lozano, Amanda R Wasylishen

Faculty, Staff and Student Publications

Daxx functions as a histone chaperone for the histone H3 variant, H3.3, and is essential for embryonic development. Daxx interacts with Atrx to form a protein complex that deposits H3.3 into heterochromatic regions of the genome, including centromeres, telomeres, and repeat loci. To advance our understanding of histone chaperone activity in vivo, we developed two Daxx mutant alleles in the mouse germline, which abolish the interactions between Daxx and Atrx (DaxxY130A), and Daxx and H3.3 (DaxxS226A). We found that the interaction between Daxx and Atrx is dispensable for viability; mice are born at the …

Novel Diagnostic And Therapeutic Approaches To Temporomandibular Dysfunction: A Narrative Review, Brendan Moxley, William Stevens, Joel Sneed, Craig Pearl

Faculty, Staff and Student Publications

Temporomandibular dysfunction (TMD) is a burgeoning area of study within the dental field. TMD is caused by abnormalities in the temporomandibular joint or muscles of mastication and can lead to pain, loss of function, and other complications. As this area of patient care receives increased focus, the ability to accurately diagnose TMD becomes paramount. The aim of this review is to summarize novel diagnostic and therapeutic techniques that have been proposed within the last approximately 3 years in order to inform readers of the cutting-edge advances in the field of TMD diagnosis and management, while also analyzing the clinical relevance …

Smad8 Is Increased In Duchenne Muscular Dystrophy And Suppresses Mir-1, Mir-133a, And Mir-133b, Meghan L Royle, Eric J Connolly, Sara Nowakowski, Jeff R Temple

Faculty, Staff and Student Publications

OBJECTIVES: Studies are beginning to document an association between sleep duration and a range of adolescent delinquent behaviors, including weapon carrying. However, little is known about whether and to what extent sleep quality - another dimension of sleep for healthy adolescent functioning - is associated with weapon carrying. We address this gap in knowledge by evaluating the role of restless sleep and sleep duration in adolescent weapon carrying.

METHODS: We analyze data from a diverse sample of 994 adolescents from Texas, USA collected in 2010. Multivariate logistic regression models estimate the association of sleep duration and restless sleep on weapon …

Immunotherapy Targeting Different Immune Compartments In Combination With Radiation Therapy Induces Regression Of Resistant Tumors, Nils-Petter Rudqvist, Maud Charpentier, Claire Lhuillier, Erik Wennerberg, Sheila Spada, Caroline Sheridan, Xi Kathy Zhou, Tuo Zhang, Silvia C Formenti, Jennifer S Sims, Alicia Alonso, Sandra Demaria

Faculty, Staff and Student Publications

Radiation therapy (RT) increases tumor response to CTLA-4 inhibition (CTLA4i) in mice and in some patients, yet deep responses are rare. To identify rational combinations of immunotherapy to improve responses we use models of triple negative breast cancer highly resistant to immunotherapy in female mice. We find that CTLA4i promotes the expansion of CD4+ T helper cells, whereas RT enhances T cell clonality and enriches for CD8+ T cells with an exhausted phenotype. Combination therapy decreases regulatory CD4+ T cells and increases effector memory, early activation and precursor exhausted CD8+ T cells. A combined gene signature comprising these three CD8+ …

Identifying The Serious Clinical Outcomes Of Adverse Reactions To Drugs By A Multi-Task Deep Learning Framework, Haochen Zhao, Peng Ni, Qichang Zhao, Xiao Liang, Di Ai, Shannon Erhardt, Jun Wang, Yaohang Li, Jianxin Wang

Faculty, Staff and Student Publications

Adverse Drug Reactions (ADRs) have a direct impact on human health. As continuous pharmacovigilance and drug monitoring prove to be costly and time-consuming, computational methods have emerged as promising alternatives. However, most existing computational methods primarily focus on predicting whether or not the drug is associated with an adverse reaction and do not consider the core issue of drug benefit-risk assessment-whether the treatment outcome is serious when adverse drug reactions occur. To this end, we categorize serious clinical outcomes caused by adverse reactions to drugs into seven distinct classes and present a deep learning framework, so-called GCAP, for predicting the …

Cost-Effectiveness Of Ticagrelor Plus Aspirin Versus Aspirin In Acute Ischaemic Stroke Or Transient Ischaemic Attack: An Economic Evaluation Of The Thales Trial, Amarjeet Tank, S Claiborne Johnston, Ritika Jain, Pierre Amarenco, Carl Mellström, Klas Rikner, Hans Denison, Per Ladenvall, Mikael Knutsson, Anders Himmelmann, Scott R Evans, Stefan James, Carlos A Molina, Yongjun Wang, Mario Ouwens

Faculty, Staff and Student Publications

OBJECTIVE: THALES demonstrated that ticagrelor plus aspirin reduced the risk of stroke or death but increased bleeding versus aspirin during the 30 days following a mild-to-moderate acute non-cardioembolic ischaemic stroke (AIS) or high-risk transient ischaemic attack (TIA). There are no cost-effectiveness analyses supporting this combination in Europe. To address this, a cost-effectiveness analysis was performed.

METHODS: Cost-effectiveness was evaluated using a decision tree and Markov model with a short-term and long-term (30-year) horizon. Stroke, mortality, bleeding and EuroQol-5 Dimension (EQ-5D) data from THALES were used to estimate short-term outcomes. Model transitions were based on stroke severity (disabling stroke was defined …

Temporal Dynamics Of Genetically Heterogeneous Extended-Spectrum Cephalosporin-Resistant Escherichia Coli Bloodstream Infections, William C Shropshire, Benjamin Strope, Selvalakshmi Selvaraj Anand, Jordan Bremer, Patrick Mcdaneld, Micah M Bhatti, Anthony R Flores, Awdhesh Kalia, Samuel A Shelburne

Faculty, Staff and Student Publications

Extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ec infections. To address the paucity of recent ESC-R-Ec molecular epidemiology data in the United States, we used whole-genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ec at a tertiary care cancer center in Houston, Texas, collected from 2016 to 2020. During the study time frame, there were 1,154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. …

Clinical And Prognostic Biomarker Value Of Blood-Circulating Inflammatory Cytokines In Hepatocellular Carcinoma, Shadi Chamseddine, Yehia I Mohamed, Sunyoung S Lee, James C Yao, Zishuo Ian Hu, Hop S Tran Cao, Lianchun Xiao, Ryan Sun, Jeffrey S Morris, Rikita I Hatia, Manal Hassan, Dan G Duda, Maria Diab, Amr Mohamed, Ahmed Nassar, Saumil Datar, Hesham M Amin, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

INTRODUCTION: Circulating inflammatory cytokines play critical roles in tumor-associated inflammation and immune responses. Recent data have suggested that several interleukins (ILs) mediate carcinogenesis in hepatocellular carcinoma (HCC). However, the predictive and prognostic value of circulating ILs is yet to be validated. Our study aimed to evaluate the association of the serum ILs with overall survival (OS) and clinicopathologic features in a large cohort of HCC patients.

METHODS: We prospectively collected data and serum samples from 767 HCC patients treated at the University of Texas MD Anderson Cancer Center between 2001 and 2014, with a median follow-up of 67.4 months (95% …

Retrospective And Real-Time Measures Of The Quantity Of E-Cigarette Use: An Ecological Momentary Assessment Study, James J Yang, Tzung-Shiang Ou, Hsien-Chang Lin, Joon Kyung Nam, Megan E Piper, Anne Buu

Faculty, Staff and Student Publications

INTRODUCTION: Quantifying e-cigarette use is challenging because of the wide variety of products and the lack of a clear, objective demarcation of a use event. This study aimed to characterize the difference between retrospective and real-time measures of the quantity of e-cigarette use and identify the covariates that may account for discrepancies between the two types of measures.

METHODS: This study analyzed data from 401 college student e-cigarette users in Indiana and Texas who responded to a web survey (retrospective) and 7-day ecological momentary assessments (EMA) (real-time) on their e-cigarette use behavior, dependence symptomatology, e-cigarette product characteristics, and use contexts …

Integrative Bayesian Tensor Regression For Imaging Genetics Applications, Yajie Liu, Nilanjana Chakraborty, Zhaohui S Qin, Suprateek Kundu

Faculty, Staff and Student Publications

Identifying biomarkers for Alzheimer's disease with a goal of early detection is a fundamental problem in clinical research. Both medical imaging and genetics have contributed informative biomarkers in literature. To further improve the performance, recently, there is an increasing interest in developing analytic approaches that combine data across modalities such as imaging and genetics. However, there are limited methods in literature that are able to systematically combine high-dimensional voxel-level imaging and genetic data for accurate prediction of clinical outcomes of interest. Existing prediction models that integrate imaging and genetic features often use region level imaging summaries, and they typically do …

Large Cross-Effect Dynamic Nuclear Polarisation Enhancements With Kilowatt Inverting Chirped Pulses At 94 Ghz, Yujie Zhao, Hassane El Mkami, Robert I Hunter, Gilles Casano, Olivier Ouari, Graham M Smith

Faculty, Staff and Student Publications

Dynamic nuclear polarisation (DNP) is a process that transfers electron spin polarisation to nuclei by applying resonant microwave radiation, and has been widely used to improve the sensitivity of nuclear magnetic resonance (NMR). Here we demonstrate new levels of performance for static cross-effect proton DNP using high peak power chirped inversion pulses at 94 GHz to create a strong polarisation gradient across the inhomogeneously broadened line of the mono-radical 4-amino TEMPO. Enhancements of up to 340 are achieved at an average power of a few hundred mW, with fast build-up times (3 s). Experiments are performed using a home-built wideband …

International Epidemiology Of Carbapenemase-Producing Escherichia Coli, Angelique E Boutzoukas, Lauren Komarow, Liang Chen, Blake Hanson, Souha S Kanj, Zhengyin Liu, Soraya Salcedo Mendoza, Karen Ordoñez, Minggui Wang, David L Paterson, Scott Evans, Lizhao Ge, Abhigya Giri, Carol Hill, Keri Baum, Robert A Bonomo, Barry Kreiswirth, Robin Patel, Cesar A Arias, Henry F Chambers, Vance G Fowler, David Van Duin

Faculty, Staff and Student Publications

BACKGROUND: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort.

METHODS: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture.

RESULTS: Of the 114 CP-Ec isolates in Consortium on resistance against …

Triple-Negative Breast Tumors Are Dependent On Mutant P53 For Growth And Survival, Denada Dibra, Sydney M Moyer, Adel K El-Naggar, Yuan Qi, Xiaoping Su, Guillermina Lozano

Faculty, Staff and Student Publications

The TP53 tumor suppressor gene is mutated early in the majority of patients with triple-negative breast cancer (TNBC). The most frequent TP53 alterations are missense mutations that contribute to tumor aggressiveness. We developed an autochthonous somatic K14-Cre driven TNBC mouse model with p53R172H and p53R245W mutations in which mutant p53 can be toggled on and off genetically while leaving the tumor microenvironment intact and wild-type for p53. These mice develop TNBCs with a median latency of 1 y. Deletion of mutant p53R172H or p53R245W in vivo in these tumors blunts their tumor growth and significantly extends survival of mice. Downstream …

Bicuspid Aortic Valve And Thoracic Aortic Disease: Further Evidence Of Clinically Silent But Deadly Risk To Family Members Of Affected Individuals, Siddharth K Prakash, Hector I Michelena, Dianna M Milewicz

Faculty, Staff and Student Publications

No abstract provided.

Exploration Of A Potential Desirability Of Outcome Ranking Endpoint For Complicated Intra-Abdominal Infections Using 9 Registrational Trials For Antibacterial Drugs, Tori Kinamon, Ramya Gopinath, Ursula Waack, Mark Needles, Daniel Rubin, Deborah Collyar, Sarah B Doernberg, Scott Evans, Toshimitsu Hamasaki, Thomas L Holland, Jessica Howard-Anderson, Henry Chambers, Vance G Fowler, Sumati Nambiar, Peter Kim, Helen W Boucher

Faculty, Staff and Student Publications

BACKGROUND: Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI).

METHODS: Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we …

Effects Of Surface Treatment Method Forming New Nano/Micro Hierarchical Structures On Attachment And Proliferation Of Osteoblast-Like Cells, Jae-Seung Im, Hyunsuk Choi, Hyun-Wook An, Tae-Yub Kwon, Min-Ho Hong

Faculty, Staff and Student Publications

Titanium (Ti) and Ti-based alloys are commonly used in dental implants, and surface modifications of dental implants are important for achieving osseointegration (i.e., direct connection between the implant surface and bone). This study investigated the effect of an eco-friendly etching solution-a hydrogen peroxide-sodium bicarbonate mixture-on the surface properties and contact angles of osteoblast adhesion and proliferation on Ti surfaces. Disk-shaped Ti specimens were prepared using different surface treatments (machining, sandblasting, and sandblasting/acid-etching), and they were immersed in the etching solution and ultrasonically cleaned. Surface characterization was performed using scanning electron microscopy, digital microscopy, contact angle analysis, and X-ray photoelectron spectroscopy. …

Pirtobrutinib In Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma, Michael L Wang, Wojciech Jurczak, Pier Luigi Zinzani, Toby A Eyre, Chan Y Cheah, Chaitra S Ujjani, Youngil Koh, Koji Izutsu, James N Gerson, Ian Flinn, Benoit Tessoulin, Alvaro J Alencar, Shuo Ma, David Lewis, Ewa Lech-Maranda, Joanna Rhodes, Krish Patel, Kami Maddocks, Nicole Lamanna, Yucai Wang, Constantine S Tam, Talha Munir, Hirokazu Nagai, Francisco Hernandez-Ilizaliturri, Anita Kumar, Timothy S Fenske, John F Seymour, Andrew D Zelenetz, Binoj Nair, Donald E Tsai, Minna Balbas, Richard A Walgren, Paolo Abada, Chunxiao Wang, Junjie Zhao, Anthony R Mato, Nirav N Shah

Faculty, Staff and Student Publications

Purpose: Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis.

Methods: Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety. …

Federated Generalized Linear Mixed Models For Collaborative Genome-Wide Association Studies, Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Federated association testing is a powerful approach to conduct large-scale association studies where sites share intermediate statistics through a central server. There are, however, several standing challenges. Confounding factors like population stratification should be carefully modeled across sites. In addition, it is crucial to consider disease etiology using flexible models to prevent biases. Privacy protections for participants pose another significant challenge. Here, we propose distributed Mixed Effects Genome-wide Association study (

Systematic Design And Data-Driven Evaluation Of Social Determinants Of Health Ontology (Sdoho), Yifang Dang, Fang Li, Xinyue Hu, Vipina K Keloth, Meng Zhang, Sunyang Fu, Muhammad F Amith, J Wilfred Fan, Jingcheng Du, Evan Yu, Hongfang Liu, Xiaoqian Jiang, Hua Xu, Cui Tao

Faculty, Staff and Student Publications

Objective: Social determinants of health (SDoH) play critical roles in health outcomes and well-being. Understanding the interplay of SDoH and health outcomes is critical to reducing healthcare inequalities and transforming a "sick care" system into a "health-promoting" system. To address the SDOH terminology gap and better embed relevant elements in advanced biomedical informatics, we propose an SDoH ontology (SDoHO), which represents fundamental SDoH factors and their relationships in a standardized and measurable way.

Material and methods: Drawing on the content of existing ontologies relevant to certain aspects of SDoH, we used a top-down approach to formally model classes, relationships, and …

A Lifecycle Framework Illustrates Eight Stages Necessary For Realizing The Benefits Of Patient-Centered Clinical Decision Support, Dean F Sittig, Aziz Boxwala, Adam Wright, Courtney Zott, Priyanka Desai, Rina Dhopeshwarkar, James Swiger, Edwin A Lomotan, Angela Dobes, Prashila Dullabh

Faculty, Staff and Student Publications

The design, development, implementation, use, and evaluation of high-quality, patient-centered clinical decision support (PC CDS) is necessary if we are to achieve the quintuple aim in healthcare. We developed a PC CDS lifecycle framework to promote a common understanding and language for communication among researchers, patients, clinicians, and policymakers. The framework puts the patient, and/or their caregiver at the center and illustrates how they are involved in all the following stages: Computable Clinical Knowledge, Patient-specific Inference, Information Delivery, Clinical Decision, Patient Behaviors, Health Outcomes, Aggregate Data, and patient-centered outcomes research (PCOR) Evidence. Using this idealized framework reminds key stakeholders that …