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2023

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Articles 27181 - 27210 of 27418

Full-Text Articles in Medicine and Health Sciences

The Impact Of Acute Calcium Intake On Bone Turnover Markers During A Training Day In Elite Male Rowers, Bronwen Lundy, Alannah K. A. Mckay, Nikita C. Fensham, Fensham, Nicolin Tee, Bryce Anderson, Aimee Morabito, Megan L. R. Ross, Marc Sim, Kathryn Ackerman, Louise M. Burke Jan 2023

The Impact Of Acute Calcium Intake On Bone Turnover Markers During A Training Day In Elite Male Rowers, Bronwen Lundy, Alannah K. A. Mckay, Nikita C. Fensham, Fensham, Nicolin Tee, Bryce Anderson, Aimee Morabito, Megan L. R. Ross, Marc Sim, Kathryn Ackerman, Louise M. Burke

Research outputs 2022 to 2026

Introduction: While an acute exercise session typically increases bone turnover markers (BTM), the impact of subsequent sessions and the interaction with pre-exercise calcium intake remains unclear despite the application to the ‘real life’ training of many competitive athletes. Methods: Using a randomized crossover design, elite male rowers (n = 16) completed two trials, a week apart, consisting of two 90-minute rowing ergometer sessions (Ex1, Ex2) separated by 150 minutes. Prior to each trial, participants consumed a high (CAL: ~1000 mg) or isocaloric low (CON: < 10 mg) calcium meal. Biochemical markers including parathyroid hormone: PTH; serum ionised calcium (iCa) and bone turnover markers (C-terminal telopeptide of type I collagen: β-CTX-I; osteocalcin: OC) were monitored from baseline to 3 hours post Ex2. Results: While each session caused perturbances of serum iCa, CAL maintained calcium concentrations above those of CON for most time points, 4.5 and 2.4 % higher post EX1 and EX2 respectively. The decrease in iCa in CON was associated with an elevation of blood PTH (p < 0.05) and β-CTX-I (p < 0.0001) over this period of repeated training sessions and their recovery, particularly during and after Ex2. Pre-exercise intake of calcium-rich foods lowered BTM over the course of a day with several training sessions. Conclusions: Pre-exercise intake of a calcium-rich meal prior to training sessions undertaken within the same day had a cumulative and prolonged effect on the stabilisation of blood iCa during exercise. In turn, this reduced the post-exercise PTH response, potentially attenuating the increase in markers of bone resorption. Such practical strategies may be integrated into the athlete’s overall sports nutrition plan, with the potential to safeguard long term bone health and reduce the risk of bone stress injuries.


Msdrp: A Deep Learning Model Based On Multisource Data For Predicting Drug Response, Haochen Zhao, Xiaoyu Zhang, Qichang Zhao, Yaohang Li, Jianxin Wang Jan 2023

Msdrp: A Deep Learning Model Based On Multisource Data For Predicting Drug Response, Haochen Zhao, Xiaoyu Zhang, Qichang Zhao, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Cancer heterogeneity drastically affects cancer therapeutic outcomes. Predicting drug response in vitro is expected to help formulate personalized therapy regimens. In recent years, several computational models based on machine learning and deep learning have been proposed to predict drug response in vitro. However, most of these methods capture drug features based on a single drug description (e.g. drug structure), without considering the relationships between drugs and biological entities (e.g. target, diseases, and side effects). Moreover, most of these methods collect features separately for drugs and cell lines but fail to consider the pairwise interactions between drugs and cell …


An Approach To Developing Benchmark Datasets For Protein Secondary Structure Segmentation From Cryo-Em Density Maps, Thu Nguyen, Yongcheng Mu, Jiangwen Sun, Jing He Jan 2023

An Approach To Developing Benchmark Datasets For Protein Secondary Structure Segmentation From Cryo-Em Density Maps, Thu Nguyen, Yongcheng Mu, Jiangwen Sun, Jing He

Computer Science Faculty Publications

More and more deep learning approaches have been proposed to segment secondary structures from cryo-electron density maps at medium resolution range (5--10Å). Although the deep learning approaches show great potential, only a few small experimental data sets have been used to test the approaches. There is limited understanding about potential factors, in data, that affect the performance of segmentation. We propose an approach to generate data sets with desired specifications in three potential factors - the protein sequence identity, structural contents, and data quality. The approach was implemented and has generated a test set and various training sets to study …


Progenitor Cell Isolation From Mouse Epididymal Adipose Tissue And Sequencing Library Construction, Qianglin Liu, Chaoyang Li, Yuxia Li, Leshan Wang, Xujia Zhang, Buhao Deng, Peidong Gao, Mohammad Shiri, Fozi Alkaifi, Junxing Zhao, Jacqueline M. Stephens, Constantine A. Simintiras, Joseph Francis, Jiangwen Sun, Xing Fu Jan 2023

Progenitor Cell Isolation From Mouse Epididymal Adipose Tissue And Sequencing Library Construction, Qianglin Liu, Chaoyang Li, Yuxia Li, Leshan Wang, Xujia Zhang, Buhao Deng, Peidong Gao, Mohammad Shiri, Fozi Alkaifi, Junxing Zhao, Jacqueline M. Stephens, Constantine A. Simintiras, Joseph Francis, Jiangwen Sun, Xing Fu

Computer Science Faculty Publications

Here, we present a protocol to isolate progenitor cells from mouse epididymal visceral adipose tissue and construct bulk RNA and assay for transposase-accessible chromatin with sequencing (ATAC-seq) libraries. We describe steps for adipose tissue collection, cell isolation, and cell staining and sorting. We then detail procedures for both ATAC-seq and RNA sequencing library construction. This protocol can also be applied to other tissues and cell types directly or with minor modifications.

For complete details on the use and execution of this protocol, please refer to Liu et al. (2023).1

*1 Liu, Q., Li, C., Deng, B., Gao, P., …


A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyag Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu Jan 2023

A Single-Cell Atlas Of Bovine Skeletal Muscle Reveals Mechanisms Regulating Intramuscular Adipogenesis And Fibrogenesis, Leshan Wang, Peidong Gao, Chaoyag Li, Qianglin Liu, Zeyang Yao, Yuxia Li, Xujia Zhang, Jiangwen Sun, Constantine Simintiras, Matthew Welborn, Kenneth Mcmillin, Stephanie Oprescu, Shihuan Kuang, Xing Fu

Computer Science Faculty Publications

Background: Intramuscular fat (IMF) and intramuscular connective tissue (IMC) are often seen in human myopathies and are central to beef quality. The mechanisms regulating their accumulation remain poorly understood. Here, we explored the possibility of using beef cattle as a novel model for mechanistic studies of intramuscular adipogenesis and fibrogenesis.

Methods: Skeletal muscle single-cell RNAseq was performed on three cattle breeds, including Wagyu (high IMF), Brahman (abundant IMC but scarce IMF), and Wagyu/Brahman cross. Sophisticated bioinformatics analyses, including clustering analysis, gene set enrichment analyses, gene regulatory network construction, RNA velocity, pseudotime analysis, and cell-cell communication analysis, were performed to elucidate …


Comparison Of Physics-Based Deformable Registration Methods For Image-Guided Neurosurgery, Nikos Chrisochoides, Yixun Liu, Fotis Drakopoulos, Andriy Kot, Panos Foteinos, Christos Tsolakis, Emmanuel Billias, Olivier Clatz, Nicholas Ayache, Andrey Fedorov, Alex Golby, Peter Black, Ron Kikinis Jan 2023

Comparison Of Physics-Based Deformable Registration Methods For Image-Guided Neurosurgery, Nikos Chrisochoides, Yixun Liu, Fotis Drakopoulos, Andriy Kot, Panos Foteinos, Christos Tsolakis, Emmanuel Billias, Olivier Clatz, Nicholas Ayache, Andrey Fedorov, Alex Golby, Peter Black, Ron Kikinis

Computer Science Faculty Publications

This paper compares three finite element-based methods used in a physics-based non-rigid registration approach and reports on the progress made over the last 15 years. Large brain shifts caused by brain tumor removal affect registration accuracy by creating point and element outliers. A combination of approximation- and geometry-based point and element outlier rejection improves the rigid registration error by 2.5 mm and meets the real-time constraints (4 min). In addition, the paper raises several questions and presents two open problems for the robust estimation and improvement of registration error in the presence of outliers due to sparse, noisy, and incomplete …


Detecting Deceptive Dark-Pattern Web Advertisements For Blind Screen-Reader Users, Satwick Ram Kodandaram, Mohan Sunkara, Sampath Jayarathna, Vikas Ashok Jan 2023

Detecting Deceptive Dark-Pattern Web Advertisements For Blind Screen-Reader Users, Satwick Ram Kodandaram, Mohan Sunkara, Sampath Jayarathna, Vikas Ashok

Computer Science Faculty Publications

Advertisements have become commonplace on modern websites. While ads are typically designed for visual consumption, it is unclear how they affect blind users who interact with the ads using a screen reader. Existing research studies on non-visual web interaction predominantly focus on general web browsing; the specific impact of extraneous ad content on blind users' experience remains largely unexplored. To fill this gap, we conducted an interview study with 18 blind participants; we found that blind users are often deceived by ads that contextually blend in with the surrounding web page content. While ad blockers can address this problem via …


Unttangling Irregular Actin Cytoskeleton Architectures In Tomograms Of The Cell With Struwwel Tracer, Salim Sazzed, Peter Scheible, Jing He, Willy Wriggers Jan 2023

Unttangling Irregular Actin Cytoskeleton Architectures In Tomograms Of The Cell With Struwwel Tracer, Salim Sazzed, Peter Scheible, Jing He, Willy Wriggers

Computer Science Faculty Publications

In this work, we established, validated, and optimized a novel computational framework for tracing arbitrarily oriented actin filaments in cryo-electron tomography maps. Our approach was designed for highly complex intracellular architectures in which a long-range cytoskeleton network extends throughout the cell bodies and protrusions. The irregular organization of the actin network, as well as cryo-electron-tomography-specific noise, missing wedge artifacts, and map dimensions call for a specialized implementation that is both robust and efficient. Our proposed solution, Struwwel Tracer, accumulates densities along paths of a specific length in various directions, starting from locally determined seed points. The highest-density paths originating …


Systematic Review Of Dyadic Psychoeducational Programs For Persons With Dementia And Their Family Caregivers, Manonita Ghosh, Melissa Dunham, Beverly O'Connell Jan 2023

Systematic Review Of Dyadic Psychoeducational Programs For Persons With Dementia And Their Family Caregivers, Manonita Ghosh, Melissa Dunham, Beverly O'Connell

Research outputs 2022 to 2026

Aims and Objectives:

Synthesising evidence for effects of dyadic psychoeducational support programs on both people with dementia and their caregivers' health and well-being.

Background:

There is an increasing need for psychoeducational support programs for people with dementia and their caregivers; therefore, it is important to identify the benefits and practical implications of the programs on the dyads.

Methods:

Guided by Joanna Briggs Institute (JBI) methodology, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, a systematic search of literature was conducted on dyadic psychoeducational programs published in English between January 2012 and January 2021 from four electronic databases. …


Relationships Among Perceptions Of Support, Experiences Of Gatekeeping, And Burnout In Counselor Educators And Supervisors, Alicia Lamar Jan 2023

Relationships Among Perceptions Of Support, Experiences Of Gatekeeping, And Burnout In Counselor Educators And Supervisors, Alicia Lamar

Dissertations

Counselor educators and supervisors carry out the responsibility of ensuring that counselors in training are competent and fit for practice. Burnout can occur when stressors in the workplace are not addressed. Engagement in the role of gatekeeper and perceptions of support can be factors that impact burnout in counselor educators. The exploration of variables that may relate to counselor educator burnout would benefit the counseling community including counselor educators, counseling students, counseling clients, and the community at large. There has been a paucity of research exploring the relationships among faculty members’ perceptions of support, experiences of gatekeeping, and burnout in …


Causal Effect Of Pm1 On Morbidity Of Cause-Specific Respiratory Diseases Based On A Negative Control Exposure, Shiyun Lv, Xiangtong Liu, Zhiwei Li, Feng Lu, Moning Guo, Mengmeng Liu, Jing Wei, Zhiyuan Wu, Siqi Yu, Shihong Li, Xia Li, Wenkang Gao, Lixin Tao, Wei Wang, Jinyuan Xin, Xiuhua Guo Jan 2023

Causal Effect Of Pm1 On Morbidity Of Cause-Specific Respiratory Diseases Based On A Negative Control Exposure, Shiyun Lv, Xiangtong Liu, Zhiwei Li, Feng Lu, Moning Guo, Mengmeng Liu, Jing Wei, Zhiyuan Wu, Siqi Yu, Shihong Li, Xia Li, Wenkang Gao, Lixin Tao, Wei Wang, Jinyuan Xin, Xiuhua Guo

Research outputs 2022 to 2026

Background: Extensive studies have linked PM2.5 and PM10 with respiratory diseases (RD). However, few is known about causal association between PM1 and morbidity of RD. We aimed to assess the causal effects of PM1 on cause-specific RD. Methods: Hospital admission data were obtained for RD during 2014 and 2019 in Beijing, China. Negative control exposure and extreme gradient boosting with SHapley Additive exPlanation was used to explore the causality and contribution between PM1 and RD. Stratified analysis by gender, age, and season was conducted. Results: A total of 1,183,591 admissions for RD were recorded. Per interquartile range (28 μg/m3) uptick …


Genetic Analysis Of Heterogeneous Subsets Of Circulating Tumour Cells From High Grade Serous Ovarian Carcinoma Patients, Du-Bois Asante, Ganendra R. K. A. Mohan, Emmanuel Acheampong, Mel R. Ziman Dr, Leslie Calapre, Tarek M. Meniawy, Elin S. Gray, Aaron B. Beasley Jan 2023

Genetic Analysis Of Heterogeneous Subsets Of Circulating Tumour Cells From High Grade Serous Ovarian Carcinoma Patients, Du-Bois Asante, Ganendra R. K. A. Mohan, Emmanuel Acheampong, Mel R. Ziman Dr, Leslie Calapre, Tarek M. Meniawy, Elin S. Gray, Aaron B. Beasley

Research outputs 2022 to 2026

Circulating tumour cells (CTCs) are heterogenous and contain genetic information from the tumour of origin. They bear specific intra- and extra-cellular protein markers aiding in their detection. However, since these markers may be shared with other rare cells in the blood, only genetic testing can confirm their malignancy. Herein, we analyse different CTC subsets using single cell whole genome DNA sequencing to validate their malignant origin. We randomly selected putative CTCs identified by immunostaining that were isolated from 4 patients with high grade serous ovarian cancer (HGSOC) and one with benign cystadenoma. We specifically targeted CTCs positive for epithelial (CK/EpCAM …


Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen Jan 2023

Novornabreak: Local Assembly For Novel Splice Junction And Fusion Transcript Detection From Rna-Seq Data, Yukun Tan, Vakul Mohanty, Shaoheng Liang, Jinzhuang Dou, Jun Ma, Kun Hee Kim, Marc Jan Bonder, Xinghua Shi, Charles Lee, Zechen Chong, Ken Chen

Faculty, Staff and Student Publications

We present novoRNABreak, a unified framework for cancer specific novel splice junction and fusion transcript detection in RNA-seq data obtained from human cancer samples. novoRNABreak is based on a local assembly model, which offers a tradeoff between the alignment-based and de novo whole transcriptome assembly (WTA) methods. This approach is accurate and sensitive in assembling novel junctions that are difficult to directly align or have multiple alignments. Additionally, it is more efficient due to the strategy that focuses on junctions rather than full length transcripts. The performance of novoRNABreak is demonstrated by a comprehensive set of experiments using synthetic data …


Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang Jan 2023

Automated Brain Metastases Segmentation With A Deep Dive Into False-Positive Detection, Hamidreza Ziyaee, Carlos E Cardenas, D Nana Yeboa, Jing Li, Sherise D Ferguson, Jason Johnson, Zijian Zhou, Jeremiah Sanders, Raymond Mumme, Laurence Court, Tina Briere, Jinzhong Yang

Faculty, Staff and Student Publications

Purpose: The clinical management of brain metastases after stereotactic radiosurgery (SRS) is difficult, because a physician must review follow-up magnetic resonance imaging (MRI) scans to determine treatment outcome, which is often labor intensive. The purpose of this study was to develop an automated framework to contour brain metastases in MRI to help treatment planning for SRS and understand its limitations.

Methods and materials: Two self-adaptive nnU-Net models trained on postcontrast 3-dimensional T1-weighted MRI scans from patients who underwent SRS were analyzed. Performance was evaluated by computing positive predictive value (PPV), sensitivity, and Dice similarity coefficient (DSC). The training and testing …


Pathologic And Molecular Insights In Nodal T-Follicular Helper Cell Lymphomas, Mario L Marques-Piubelli, Catalina Amador, Francisco Vega Jan 2023

Pathologic And Molecular Insights In Nodal T-Follicular Helper Cell Lymphomas, Mario L Marques-Piubelli, Catalina Amador, Francisco Vega

Faculty, Staff and Student Publications

T-follicular helper (TFH) cells are one of the T-cell subsets with a critical role in the regulation of germinal center (GC) reactions. TFH cells contribute to the positive selection of GC B-cells and promote plasma cell differentiation and antibody production. TFH cells express a unique phenotype characterized by PD-1hi, ICOShi, CD40Lhi, CD95hi, CTLAhi, CCR7lo, and CXCR5hi . Three main subtypes of nodal TFH lymphomas have been described: 1) angioimmunoblastic-type, 2) follicular-type, and 3) not otherwise specified (NOS). The diagnosis of these neoplasms can be challenging, and it is rendered based on a combination of clinical, laboratory, histopathologic, immunophenotypic, and molecular …


When Guilt Works: A Comprehensive Meta-Analysis Of Guilt Appeals, Wei Peng, Qian Huang, Bingjing Mao, Di Lun, Ekaterina Malova, Jazmyne V Simmons, Nick Carcioppolo Jan 2023

When Guilt Works: A Comprehensive Meta-Analysis Of Guilt Appeals, Wei Peng, Qian Huang, Bingjing Mao, Di Lun, Ekaterina Malova, Jazmyne V Simmons, Nick Carcioppolo

Faculty, Staff and Student Publications

Introduction: Guilt appeals are widely used as a persuasive approach in various areas of practice. However, the strength and direction of the persuasive effects of guilt appeals are mixed, which could be influenced by theoretical and methodological factors.

Method: The present study is a comprehensive meta-analysis of 26 studies using a random-effects model to assess the persuasive effects of guilt appeals. In total, 127 effect sizes from seven types of persuasive outcomes (i.e., guilt, attitude, behavior, behavioral intention, non-guilt emotions, motivation, and cognition) were calculated based on 7,512 participants.

Results: The analysis showed a small effect size of guilt appeals …


Changes In Distribution Of Severe Neurologic Involvement In Us Pediatric Inpatients With Covid-19 Or Multisystem Inflammatory Syndrome In Children In 2021 Vs 2020., Kerri L. Larovere, Tina Y. Poussaint, Cameron C. Young, Margaret M. Newhams, Suden Kucukak, Katherine Irby, Michele Kong, Stephanie P. Schwartz, Tracie C. Walker, Melania M. Bembea, Kari Wellnitz, Kevin M. Havlin, Natalie Z. Cvijanovich, Mark W. Hall, Julie C. Fitzgerald, Jennifer E. Schuster, Charlotte V. Hobbs, Natasha B. Halasa, Aalok R. Singh, Elizabeth H. Mack, Tamara T. Bradford, Shira J. Gertz, Adam J. Schwarz, Katri V. Typpo, Laura L. Loftis, John S. Giuliano, Steven M. Horwitz, Katherine V. Biagas, Katharine N. Clouser, Courtney M. Rowan, Aline B. Maddux, Vijaya L. Soma, Christopher J. Babbitt, Cassyanne L. Aguiar, Amanda R. Kolmar, Sabrina M. Heidemann, Helen Harvey, Laura D. Zambrano, Angela P. Campbell, Adrienne G. Randolph, Overcoming Covid-19 Investigators Jan 2023

Changes In Distribution Of Severe Neurologic Involvement In Us Pediatric Inpatients With Covid-19 Or Multisystem Inflammatory Syndrome In Children In 2021 Vs 2020., Kerri L. Larovere, Tina Y. Poussaint, Cameron C. Young, Margaret M. Newhams, Suden Kucukak, Katherine Irby, Michele Kong, Stephanie P. Schwartz, Tracie C. Walker, Melania M. Bembea, Kari Wellnitz, Kevin M. Havlin, Natalie Z. Cvijanovich, Mark W. Hall, Julie C. Fitzgerald, Jennifer E. Schuster, Charlotte V. Hobbs, Natasha B. Halasa, Aalok R. Singh, Elizabeth H. Mack, Tamara T. Bradford, Shira J. Gertz, Adam J. Schwarz, Katri V. Typpo, Laura L. Loftis, John S. Giuliano, Steven M. Horwitz, Katherine V. Biagas, Katharine N. Clouser, Courtney M. Rowan, Aline B. Maddux, Vijaya L. Soma, Christopher J. Babbitt, Cassyanne L. Aguiar, Amanda R. Kolmar, Sabrina M. Heidemann, Helen Harvey, Laura D. Zambrano, Angela P. Campbell, Adrienne G. Randolph, Overcoming Covid-19 Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.

OBJECTIVE: To provide an update on the spectrum of SARS-CoV-2-related neurologic involvement among children and adolescents in 2021.

DESIGN, SETTING, AND PARTICIPANTS: Case series investigation of patients reported to public health surveillance hospitalized with SARS-CoV-2-related illness between December 15, 2020, and December 31, 2021, in 55 US hospitals in 31 states with follow-up at hospital discharge. A total of 2253 patients were enrolled during the investigation period. Patients suspected of having …


Association Of Central Venous Saturation And Serum Lactate With Outcomes In Veno-Arterial Extracorporeal Membrane Oxygenation., Rohit S. Loomba, Enrique G. Villarreal, Juan S. Farias, Saul Flores Jan 2023

Association Of Central Venous Saturation And Serum Lactate With Outcomes In Veno-Arterial Extracorporeal Membrane Oxygenation., Rohit S. Loomba, Enrique G. Villarreal, Juan S. Farias, Saul Flores

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete Jan 2023

Sociodemographic Differences In Menthol Cigarette Use In The United States, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

Background: Menthol cigarette use is associated with higher smoking initiation and reduced smoking cessation. We investigated sociodemographic differences in menthol and nonmenthol cigarette use in the United States.

Methods: We used the most recent available data from the May 2019 wave of the nationally-representative Tobacco Use Supplement to the Current Population Survey. The survey weights were used to estimate the national prevalence of individuals who currently smoke among individuals who use menthol and nonmenthol cigarettes. Survey-weighted logistic regression methods were used to estimate the association of menthol cigarette use with formerly smoking cigarettes and attempting to quit within the past …


Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, Greg L Hura, John A Tainer Jan 2023

Applying Ht-Saxs To Chemical Ligand Screening, Chris A Brosey, Runze Shen, Davide Moiani, Darin E Jones, Kathryn Burnett, Greg L Hura, John A Tainer

Faculty, Staff and Student Publications

Chemical probes are invaluable tools for investigating essential biological processes. Understanding how small-molecule probes engage biomolecular conformations is critical to developing their functional selectivity. High-throughput solution X-ray scattering is well-positioned to profile target-ligand complexes during probe development, bringing conformational insight and selection to traditional ligand binding assays. Access to high-quality synchrotron SAXS datasets and high-throughput data analysis now allows routine academic users to incorporate conformational information into small-molecule development pipelines. Here we describe a general approach for benchmarking and preparing HT-SAXS chemical screens from small fragment libraries. Using the allosteric oxidoreductase Apoptosis-Inducing Factor (AIF) as an exemplary system, we illustrate …


Adverse Events Of Immune Checkpoint Therapy Alone Versus When Combined With Vascular Endothelial Growth Factor Inhibitors: A Pooled Meta-Analysis Of 1735 Patients, Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Shailender Bhatia, Petros Grivas, Raed Benkhadra, Omar Alhalabi Jan 2023

Adverse Events Of Immune Checkpoint Therapy Alone Versus When Combined With Vascular Endothelial Growth Factor Inhibitors: A Pooled Meta-Analysis Of 1735 Patients, Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Shailender Bhatia, Petros Grivas, Raed Benkhadra, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.

Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and …


Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg Jan 2023

Cd73-Generated Extracellular Adenosine Promotes Resolution Of Neutrophil-Mediated Tissue Injury And Restrains Metaplasia In Pancreatitis, Baylee J O'Brien, Erika Y Faraoni, Lincoln N Strickland, Zhibo Ma, Victoria Mota, Samantha Mota, Xuebo Chen, Tingting Mills, Holger K Eltzschig, Kathleen E Delgiorno, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatitis is currently the leading cause of gastrointestinal hospitalizations in the US. This condition occurs in response to abdominal injury, gallstones, chronic alcohol consumption or, less frequently, the cause remains idiopathic. CD73 is a cell surface ecto‐5′‐nucleotidase that generates extracellular adenosine, which can contribute to resolution of inflammation by binding adenosine receptors on infiltrating immune cells. We hypothesized genetic deletion of CD73 would result in more severe pancreatitis due to decreased generation of extracellular adenosine. CD73 knockout (CD73 −/−) and C57BL/6 (wild type, WT) mice were used to evaluate the progression and response of caerulein‐induced acute and chronic pancreatitis. …


Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed Jan 2023

Positron Emission Tomography Derived Metrics In Relapsed Or Refractory Large B-Cell Lymphoma With Residual Disease Before Autologous Stem Cell Transplant, Hua-Jay J Cherng, Guofan Xu, Lei Feng, Raphael Steiner, Luis Fayad, Paolo Strati, Ranjit Nair, Loretta J Nastoupil, Hun Ju Lee, Sattva S Neelapu, Christopher R Flowers, Maria Rodriguez, Michael Wang, Fredrick Hagemeister, Chelsea C Pinnix, Jeremy Ramdial, Samer Srour, Yago Nieto, Katayoun Rezvani, Richard Champlin, Partow Kebriaei, Jason Westin, Homer A Macapinlac, Elizabeth Shpall, Sairah Ahmed

Faculty, Staff and Student Publications

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, …


Nutritional Management Of The Infant With Chronic Kidney Disease Stages 2-5 And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Dieter Haffner, Christina L. Nelms, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, José Renken-Terhaerdt, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Rukshana Shroff Jan 2023

Nutritional Management Of The Infant With Chronic Kidney Disease Stages 2-5 And On Dialysis., Vanessa Shaw, Caroline Anderson, An Desloovere, Larry A. Greenbaum, Dieter Haffner, Christina L. Nelms, Fabio Paglialonga, Nonnie Polderman, Leila Qizalbash, José Renken-Terhaerdt, Stella Stabouli, Jetta Tuokkola, Johan Vande Walle, Bradley A. Warady, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

The nutritional management of children with chronic kidney disease (CKD) is of prime importance in meeting the challenge of maintaining normal growth and development in this population. The objective of this review is to integrate the Pediatric Renal Nutrition Taskforce clinical practice recommendations for children with CKD stages 2-5 and on dialysis, as they relate to the infant from full term birth up to 1 year of age, for healthcare professionals, including dietitians, physicians, and nurses. It addresses nutritional assessment, energy and protein requirements, delivery of the nutritional prescription, and necessary dietary modifications in the case of abnormal serum levels …


The Kynurenine Pathway Presents Multi-Faceted Metabolic Vulnerabilities In Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Ali Hussein Abdel Sater, Edwin Ostrin, Samir Hanash, Johannes F Fahrmann Jan 2023

The Kynurenine Pathway Presents Multi-Faceted Metabolic Vulnerabilities In Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Ali Hussein Abdel Sater, Edwin Ostrin, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) …


Impact Of Region-Of-Interest Size On Immune Profiling Using Multiplex Immunofluorescence Tyramide Signal Amplification For Paraffin-Embedded Tumor Tissues, Baohua Sun, Caddie Laberiano-Fernández, Ruth Salazar-Alejo, Jiexin Zhang, Jose Luis Solorzano Rendon, Jack Lee, Luisa Maren Solis Soto, Ignacio Ivan Wistuba, Edwin Roger Parra Jan 2023

Impact Of Region-Of-Interest Size On Immune Profiling Using Multiplex Immunofluorescence Tyramide Signal Amplification For Paraffin-Embedded Tumor Tissues, Baohua Sun, Caddie Laberiano-Fernández, Ruth Salazar-Alejo, Jiexin Zhang, Jose Luis Solorzano Rendon, Jack Lee, Luisa Maren Solis Soto, Ignacio Ivan Wistuba, Edwin Roger Parra

Faculty, Staff and Student Publications

Introduction: Representative regions of interest (ROIs) analysis from the whole slide images (WSI) are currently being used to study immune markers by multiplex immunofluorescence (mIF) and single immunohistochemistry (IHC). However, the amount of area needed to be analyzed to be representative of the entire tumor in a WSI has not been defined.

Methods: We labeled tumor-associated immune cells by mIF and single IHC in separate cohorts of non-small cell lung cancer (NSCLC) samples and we analyzed them as whole tumor area as well as using different number of ROIs to know how much area will be need to represent the …


Exploration Of Cancer Associated Fibroblasts Phenotypes In The Tumor Microenvironment Of Classical And Pleomorphic Invasive Lobular Carcinoma, Harsh Batra, Qingqing Ding, Renganayaki Pandurengan, Heladio Ibarguen, Neus Bota Rabassedas, Aysegul Sahin, Ignacio Wistuba, Edwin Roger Parra, Maria Gabriela Raso Jan 2023

Exploration Of Cancer Associated Fibroblasts Phenotypes In The Tumor Microenvironment Of Classical And Pleomorphic Invasive Lobular Carcinoma, Harsh Batra, Qingqing Ding, Renganayaki Pandurengan, Heladio Ibarguen, Neus Bota Rabassedas, Aysegul Sahin, Ignacio Wistuba, Edwin Roger Parra, Maria Gabriela Raso

Faculty, Staff and Student Publications

UNLABELLED: As the second most common subtype of breast carcinoma, Invasive Lobular Carcinoma (ILC) microenvironment features have not been thoroughly explored. ILC has different histological subtypes and elucidating differences in their microenvironments could lead to a comprehensive development of cancer therapies. We designed a custom-made cancer associated fibroblast (CAFs) panel and used multiplex immunofluorescence to identify the differences in tumor microenvironment between Classic ILC and Pleomorphic ILC.

MATERIALS AND METHODS: Multiplex immunofluorescence were performed on formalin fixed paraffin embedded tissues using Opal-7 color kit. The antibodies used for phenotyping CAFs were Pan CK (AE1/AE3), CD45, A-SMA, FAP, S100, Thy-1 with …


Prospective In Silico Evaluation Of Cone-Beam Computed Tomography-Guided Stereotactic Adaptive Radiation Therapy (Ct-Star) For The Ablative Treatment Of Ultracentral Thoracic Disease, Joshua P Schiff, Eric Laugeman, Hayley B Stowe, Xiaodong Zhao, Jessica Hilliard, Ellie Hawk, Jesiah Watkins, Casey Hatscher, Shahed N Badiyan, Pamela P Samson, Geoffrey D Hugo, Clifford G Robinson, Alex T Price, Lauren E Henke Jan 2023

Prospective In Silico Evaluation Of Cone-Beam Computed Tomography-Guided Stereotactic Adaptive Radiation Therapy (Ct-Star) For The Ablative Treatment Of Ultracentral Thoracic Disease, Joshua P Schiff, Eric Laugeman, Hayley B Stowe, Xiaodong Zhao, Jessica Hilliard, Ellie Hawk, Jesiah Watkins, Casey Hatscher, Shahed N Badiyan, Pamela P Samson, Geoffrey D Hugo, Clifford G Robinson, Alex T Price, Lauren E Henke

2020-Current year OA Pubs

PURPOSE: We conducted a prospective, in silico study to evaluate the feasibility of cone-beam computed tomography (CBCT)-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of ultracentral thoracic cancers (NCT04008537). We hypothesized that CT-STAR would reduce dose to organs at risk (OARs) compared with nonadaptive stereotactic body radiation therapy (SBRT) while maintaining adequate tumor coverage.

METHODS AND MATERIALS: Patients who were already receiving radiation therapy for ultracentral thoracic malignancies underwent 5 additional daily CBCTs on the ETHOS system as part of a prospective imaging study. These were used to simulate CT-STAR, in silico

RESULTS: Seven patients were accrued, 6 with …


Phantom-Based Quality Assurance Of A Clinical Dose Accumulation Technique Used In An Online Adaptive Radiation Therapy Platform, Borna Maraghechi, Thomas Mazur, Dao Lam, Alex Price, Lauren Henke, Hyun Kim, Geoffrey D Hugo, Bin Cai Jan 2023

Phantom-Based Quality Assurance Of A Clinical Dose Accumulation Technique Used In An Online Adaptive Radiation Therapy Platform, Borna Maraghechi, Thomas Mazur, Dao Lam, Alex Price, Lauren Henke, Hyun Kim, Geoffrey D Hugo, Bin Cai

2020-Current year OA Pubs

PURPOSE: This study aimed to develop a routine quality assurance method for a dose accumulation technique provided by a radiation therapy platform for online treatment adaptation.

METHODS AND MATERIALS: Two commonly used phantoms were selected for the dose accumulation QA: Electron density and anthropomorphic pelvis. On a computed tomography (CT) scan of the electron density phantom, 1 target (gross tumor volume [GTV]; insert at 6 o'clock), a subvolume within this target, and 7 organs at risk (OARs; other inserts) were contoured in the treatment planning system (TPS). Two adaptation sessions were performed in which the GTV was recontoured, first at …


Elevated Liver Glycogenolysis Mediates Higher Blood Glucose During Acute Exercise In Barth Syndrome, George G. Schweitzer, Grace L. Ditzenberger, Curtis C. Hughey, Brian N. Finck, Michael R. Martino, Christina A. Pacak, Barry J. Byrne, William Todd Cade Jan 2023

Elevated Liver Glycogenolysis Mediates Higher Blood Glucose During Acute Exercise In Barth Syndrome, George G. Schweitzer, Grace L. Ditzenberger, Curtis C. Hughey, Brian N. Finck, Michael R. Martino, Christina A. Pacak, Barry J. Byrne, William Todd Cade

2020-Current year OA Pubs

UNLABELLED: Barth syndrome (BTHS) is an X-linked recessive genetic disorder due to mutations in the Tafazzin (TAFAZZIN) gene that lead to cardiac and skeletal muscle mitochondrial dysfunction. Previous studies in humans with BTHS demonstrate that the defects in muscle mitochondrial oxidative metabolism result in an enhanced reliance on anaerobic metabolism during exercise to meet energy demands of muscular work. During exercise, the liver normally increases glucose production via glycogenolysis and gluconeogenesis to match the elevated rate of muscle glucose uptake and meet the ATP requirements of working muscle. However, the impact of Tafazzin deficiency on hepatic glucose production and the …