Medicine and Health Sciences Commons^™

Magnetic Resonance-Guided Radiation Therapy For Head And Neck Cancers, Danny Lavigne, Sweet Ping Ng, Brian O'Sullivan, Phuc Felix Nguyen-Tan, Edith Filion, Laurent Létourneau-Guillon, Clifton D Fuller, Houda Bahig

Faculty, Staff and Student Publications

Despite the significant evolution of radiation therapy (RT) techniques in recent years, many patients with head and neck cancer still experience significant toxicities during and after treatments. The increased soft tissue contrast and functional sequences of magnetic resonance imaging (MRI) are particularly attractive in head and neck cancer and have led to the increasing development of magnetic resonance-guided RT (MRgRT). This approach refers to the inclusion of the additional information acquired from a diagnostic or planning MRI in radiation treatment planning, and now extends to online high-quality daily imaging generated by the recently developed MR-Linac. MRgRT holds numerous potentials, including …

A Machine Learning-Based Method For Automatically Identifying Novel Cells In Annotating Single-Cell Rna-Seq Data, Ziyi Li, Yizhuo Wang, Irene Ganan-Gomez, Simona Colla, Kim-Anh Do

Faculty, Staff and Student Publications

MOTIVATION: Single-cell RNA sequencing (scRNA-seq) has been widely used to decompose complex tissues into functionally distinct cell types. The first and usually the most important step of scRNA-seq data analysis is to accurately annotate the cell labels. In recent years, many supervised annotation methods have been developed and shown to be more convenient and accurate than unsupervised cell clustering. One challenge faced by all the supervised annotation methods is the identification of the novel cell type, which is defined as the cell type that is not present in the training data, only exists in the testing data. Existing methods usually …

Standards In Semen Examination: Publishing Reproducible And Reliable Data Based On High-Quality Methodology, Lars Björndahl, Christopher L R Barratt, David Mortimer, Ashok Agarwal, Robert J Aitken, Juan G Alvarez, Natalie Aneck-Hahn, Stefan Arver, Elisabetta Baldi, Lluís Bassas, Florence Boitrelle, Riana Bornman, Douglas T Carrell, José A Castilla, Gerardo Cerezo Parra, Jerome H Check, Patricia S Cuasnicu, Sally Perreault Darney, Christiaan De Jager, Christopher J De Jonge, Joël R Drevet, Erma Z Drobnis, Stefan S Du Plessis, Michael L Eisenberg, Sandro C Esteves, Evangelini A Evgeni, Alberto Ferlin, Nicolas Garrido, Aleksander Giwercman, Ilse G F Goovaerts, Trine B Haugen, Ralf Henkel, Lars Henningsohn, Marie-Claude Hofmann, James M Hotaling, Piotr Jedrzejczak, Pierre Jouannet, Niels Jørgensen, Jackson C Kirkman Brown, Csilla Krausz, Maciej Kurpisz, Ulrik Kvist, Dolores J Lamb, Hagai Levine, Kate L Loveland, Robert I Mclachlan, Ali Mahran, Liana Maree, Sarah Martins Da Silva, Michael T Mbizvo, Andreas Meinhardt, Roelof Menkveld, Sharon T Mortimer, Sergey Moskovtsev, Charles H Muller, Maria José Munuce, Monica Muratori, Craig Niederberger, Cristian O'Flaherty, Rafael Oliva, Willem Ombelet, Allan A Pacey, Michael A Palladino, Ranjith Ramasamy, Liliana Ramos, Nathalie Rives, Eduardo Rs Roldan, Susan Rothmann, Denny Sakkas, Andrea Salonia, Maria Cristina Sánchez-Pozo, Rosanna Sapiro, Stefan Schlatt, Peter N Schlegel, Hans-Christian Schuppe, Rupin Shah, Niels E Skakkebæk, Katja Teerds, Igor Toskin, Herman Tournaye, Paul J Turek, Gerhard Van Der Horst, Monica Vazquez-Levin, Christina Wang, Alex Wetzels, Theodosia Zeginiadou, Armand Zini

Faculty, Staff and Student Publications

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

Inhibition Of Colorectal Cancer Tumorigenesis By Ursolic Acid And Doxorubicin Is Mediated By Targeting The Akt Signaling Pathway And Activating The Hippo Signaling Pathway, Masashi Fujita, Mei-Ju May Chen, Doris Rieko Siwak, Shota Sasagawa, Ayako Oosawa-Tatsuguchi, Koji Arihiro, Atsushi Ono, Ryoichi Miura, Kazuhiro Maejima, Hiroshi Aikata, Masaki Ueno, Shinya Hayami, Hiroki Yamaue, Kazuaki Chayama, Ju-Seog Lee, Yiling Lu, Gordon B Mills, Han Liang, Satoshi S Nishizuka, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Primary liver cancer is a heterogeneous disease in terms of its etiology, histology, and therapeutic response. Concurrent proteomic and genomic characterization of a large set of clinical liver cancer samples can help elucidate the molecular basis of heterogeneity and thus serve as a valuable resource for personalized liver cancer treatment. In this study, we perform proteomic profiling of ~300 proteins on 259 primary liver cancer tissues with reverse-phase protein arrays, mutational analysis using whole genome sequencing and transcriptional analysis with RNA-Seq. Patients are of Japanese ethnic background and mainly HBV or HCV positive, providing insight into this important liver cancer …

Proteo-Genomic Characterization Of Virus-Associated Liver Cancers Reveals Potential Subtypes And Therapeutic Targets, Masashi Fujita, Mei-Ju May Chen, Doris Rieko Siwak, Shota Sasagawa, Ayako Oosawa-Tatsuguchi, Koji Arihiro, Atsushi Ono, Ryoichi Miura, Kazuhiro Maejima, Hiroshi Aikata, Masaki Ueno, Shinya Hayami, Hiroki Yamaue, Kazuaki Chayama, Ju-Seog Lee, Yiling Lu, Gordon B Mills, Han Liang, Satoshi S Nishizuka, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Primary liver cancer is a heterogeneous disease in terms of its etiology, histology, and therapeutic response. Concurrent proteomic and genomic characterization of a large set of clinical liver cancer samples can help elucidate the molecular basis of heterogeneity and thus serve as a valuable resource for personalized liver cancer treatment. In this study, we perform proteomic profiling of ~300 proteins on 259 primary liver cancer tissues with reverse-phase protein arrays, mutational analysis using whole genome sequencing and transcriptional analysis with RNA-Seq. Patients are of Japanese ethnic background and mainly HBV or HCV positive, providing insight into this important liver cancer …

Range-Bounded Adaptive Therapy In Metastatic Prostate Cancer, Renee Brady-Nicholls, Heiko Enderling

Faculty, Staff and Student Publications

Adaptive therapy with abiraterone acetate (AA), whereby treatment is cycled on and off, has been presented as an alternative to continuous therapy for metastatic castration resistant prostate cancer (mCRPC). It is hypothesized that cycling through treatment allows sensitive cells to competitively suppress resistant cells, thereby increasing the amount of time that treatment is effective. It has been proposed that there exists a subset of patients for whom this competition can be enhanced through slight modifications. Here, we investigate how adaptive AA can be modified to extend time to progression using a simple mathematical model of stem cell, non-stem cell, and …

The Detection Of Periodic Reemergence Events Of Sars-Cov-2 Delta Strain In Communities Dominated By Omicron., Claire E. Westcott, Kevin J. Sokoloski, Eric C. Rouchka, Julia H. Chariker, Rochelle H. Holm, Ray A. Yeager, Joseph B. Moore Iv, Erin M. Elliott, Daymond Talley, Aruni Bhatnagar

Faculty and Staff Scholarship

Despite entering an endemic phase, SARS-CoV-2 remains a significant burden to public health across the global community. Wastewater sampling has consistently proven utility to understanding SARS-CoV-2 prevalence trends and genetic variation as it represents a less biased assessment of the corresponding communities. Here, we report that ongoing monitoring of SARS-CoV-2 genetic variation in samples obtained from the wastewatersheds of the city of Louisville in Jefferson county Kentucky has revealed the periodic reemergence of the Delta strain in the presence of the presumed dominant Omicron strain. Unlike previous SARS-CoV-2 waves/emergence events, the Delta reemergence events were geographically restricted in the community …

Challenges And Opportunities Associated With The Md Anderson Impact2 Randomized Study In Precision Oncology, Henry Hiep Vo, Siqing Fu, David S Hong, Daniel D Karp, Sarina Piha-Paul, Vivek Subbiah, Filip Janku, Aung Naing, Timothy A Yap, Jordi Rodon, Jaffer A Ajani, Carrie Cartwright, Amber Johnson, I-Wen Song, Jennifer Beck, Michael Kahle, Graciela M Nogueras-Gonzalez, Vincent Miller, Calvin Chao, David J Vining, Donald A Berry, Funda Meric-Bernstam, Apostolia-Maria Tsimberidou

Faculty, Staff and Student Publications

We investigated the challenges of conducting IMPACT2, an ongoing randomized study that evaluates molecular testing and targeted therapy (ClinicalTrials.gov: NCT02152254). Patients with metastatic cancer underwent tumor profiling and were randomized between the two arms when eligibility criteria were met (Part A). In Part B, patients who declined randomization could choose the study arm. In Part A, 69 (21.8%) of 317 patients were randomized; 78.2% were not randomized because of non-targetable alterations (39.8%), unavailability of clinical trial (21.8%), other reasons (12.6%), or availability of US Food and Drug Administration (FDA)-approved drugs for the indication (4.1%). In Part B, 32 (20.4%) of …

Loneliness And Alcohol-Related Problems Among College Students Who Report Binge Drinking Behavior: The Moderating Role Of Food And Alcohol Disturbance, Luke Herchenroeder, Stacy M Post, Michelle L Stock, Ellen W Yeung

Faculty, Staff and Student Publications

Loneliness and alcohol misuse are common among college students and pose a threat to public health. To better understand the longitudinal association between these public health concerns we examined food and alcohol disturbance (FAD; i.e., restricting one's caloric intake prior to drinking) as a moderator in the association between loneliness and alcohol-related problems. Participants were 456 college students from a mid-sized university who engaged in past 30-day binge drinking. The majority of participants identified as being White (67.1%), female (78.1%), and reported a mean age of 19.61 (SD = 1.54) years. Participants completed two surveys (3 weeks apart) over the …

The Tumor Invasion Paradox In Cancer Stem Cell-Driven Solid Tumors, Alexandra Shyntar, Ashna Patel, Meghan Rhodes, Heiko Enderling, Thomas Hillen

Faculty, Staff and Student Publications

Cancer stem cells (CSCs) are key in understanding tumor growth and tumor progression. A counterintuitive effect of CSCs is the so-called tumor growth paradox: the effect where a tumor with a higher death rate may grow larger than a tumor with a lower death rate. Here we extend the modeling of the tumor growth paradox by including spatial structure and considering cancer invasion. Using agent-based modeling and a corresponding partial differential equation model, we demonstrate and prove mathematically a tumor invasion paradox: a larger cell death rate can lead to a faster invasion speed. We test this result on a …

Dysfunctional Glymphatic System With Disrupted Aquaporin 4 Expression Pattern On Astrocytes Causes Bacterial Product Accumulation In The Csf During Pneumococcal Meningitis, Jaqueline S Generoso, Sigrun Thorsdottir, Allan Collodel, Diogo Dominguini, Roberta R E Santo, Fabricia Petronilho, Tatiana Barichello, Federico Iovino

Faculty, Staff and Student Publications

Pneumococcal meningitis, inflammation of the meninges due to an infection of the Central Nervous System caused by Streptococcus pneumoniae (the pneumococcus), is the most common form of community-acquired bacterial meningitis globally. Aquaporin 4 (AQP4) water channels on astrocytic end feet regulate the solute transport of the glymphatic system, facilitating the exchange of compounds between the brain parenchyma and the cerebrospinal fluid (CSF), which is important for the clearance of waste away from the brain. Wistar rats, subjected to either pneumococcal meningitis or artificial CSF (sham control), received Evans blue-albumin (EBA) intracisternally. Overall, the meningitis group presented a significant impairment of …

Systematic Analysis Of Mobile Genetic Elements Mediating Β-Lactamase Gene Amplification In Noncarbapenemase-Producing Carbapenem-Resistant Enterobacterales Bloodstream Infections, W C Shropshire, A Konovalova, P Mcdaneld, M Gohel, B Strope, P Sahasrabhojane, C N Tran, D Greenberg, J Kim, X Zhan, S Aitken, M Bhatti, T C Savidge, T J Treangen, B M Hanson, C A Arias, S A Shelburne

Faculty, Staff and Student Publications

Noncarbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE) are increasingly recognized as important contributors to prevalent carbapenem-resistant Enterobacterales (CRE) infections. However, there is limited understanding of mechanisms underlying non-CP-CRE causing invasive disease. Long- and short-read whole-genome sequencing was used to elucidate carbapenem nonsusceptibility determinants in Enterobacterales bloodstream isolates at MD Anderson Cancer Center in Houston, Texas. We investigated carbapenem nonsusceptible Enterobacterales (CNSE) mechanisms (i.e., isolates with carbapenem intermediate resistance phenotypes or greater) through a combination of phylogenetic analysis, antimicrobial resistance gene detection/copy number quantification, porin assessment, and mobile genetic element (MGE) characterization. Most CNSE isolates sequenced were non-CP-CRE (41/79; 51.9%), whereas 25.3% (20/79) were …

Evaluation Of Allogeneic And Autologous Membrane-Bound Il-21-Expanded Nk Cells For Chronic Lymphocytic Leukemia Therapy, Max Yano, Chia Sharpe, J Rachel Lance, Janani Ravikrishnan, Kevan Zapolnik, Xiaokui Mo, Jennifer A Woyach, Deepa Sampath, Adam S Kittai, Sumithira Vasu, Seema Bhat, Kerry A Rogers, Dean A Lee, Natarajan Muthusamy, John C Byrd

Faculty, Staff and Student Publications

Successes with anti-CD20 antibodies in chronic lymphocytic leukemia (CLL) and enhanced activity of Fc-engineered vs unmodified antibody therapy suggest a potentially impactful role for natural killer (NK) cells and other innate immune cells in controlling this disease. Stimulated NK cells have shown promise as a cellular therapy, but their application has been constrained by limited expansion capacity and low cytotoxic activity against CLL cells. Here, we demonstrate that both healthy donor-derived and CLL patient-derived NK cells expand rapidly when stimulated with feeder cells expressing membrane-bound interleukin-21 (mbIL-21) and have potent cytotoxic activity against allogeneic or autologous CLL cells. Combination with …

Ubr2 Targets Myosin Heavy Chain Iib And Iix For Degradation: Molecular Mechanism Essential For Cancer-Induced Muscle Wasting, Song Gao, Guohua Zhang, Zicheng Zhang, James Z Zhu, Li Li, Yong Zhou, George G Rodney, Reem S Abo-Zahrah, Lindsey Anderson, Jose M Garcia, Yong Tae Kwon, Yi-Ping Li

Faculty, Staff and Student Publications

Cancer cachexia is a lethal metabolic syndrome featuring muscle wasting with preferential loss of fast-twitching muscle mass through an undefined mechanism. Here, we show that cancer induces muscle wasting by selectively degrading myosin heavy chain (MHC) subtypes IIb and IIx through E3 ligase UBR2-mediated ubiquitylation. Induction of MHC loss and atrophy in C2C12 myotubes and mouse tibialis anterior (TA) by murine cancer cells required UBR2 up-regulation by cancer. Genetic gain or loss of UBR2 function inversely altered MHC level and muscle mass in TA of tumor-free mice. UBR2 selectively interacted with and ubiquitylated MHC-IIb and MHC-IIx through its substrate recognition …

Biomarkers Beyond Brca: Promising Combinatorial Treatment Strategies In Overcoming Resistance To Parp Inhibitors, Yu-Yi Chu, Clinton Yam, Hirohito Yamaguchi, Mien-Chie Hung

Faculty, Staff and Student Publications

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) exploit the concept of synthetic lethality and offer great promise in the treatment of tumors with deficiencies in homologous recombination (HR) repair. PARPi exert antitumor activity by blocking Poly(ADP-ribosyl)ation (PARylation) and trapping PARP1 on damaged DNA. To date, the U.S. Food and Drug Administration (FDA) has approved four PARPi for the treatment of several cancer types including ovarian, breast, pancreatic and prostate cancer. Although patients with HR-deficient tumors benefit from PARPi, majority of tumors ultimately develop acquired resistance to PARPi. Furthermore, even though BRCA1/2 mutations are commonly used as markers of PARPi sensitivity in …

Summit: An Integrative Approach For Better Transcriptomic Data Imputation Improves Causal Gene Identification, Zichen Zhang, Ye Eun Bae, Jonathan R Bradley, Lang Wu, Chong Wu

Faculty, Staff and Student Publications

Genes with moderate to low expression heritability may explain a large proportion of complex trait etiology, but such genes cannot be sufficiently captured in conventional transcriptome-wide association studies (TWASs), partly due to the relatively small available reference datasets for developing expression genetic prediction models to capture the moderate to low genetically regulated components of gene expression. Here, we introduce a method, the Summary-level Unified Method for Modeling Integrated Transcriptome (SUMMIT), to improve the expression prediction model accuracy and the power of TWAS by using a large expression quantitative trait loci (eQTL) summary-level dataset. We apply SUMMIT to the eQTL summary-level …

The Impact Of Covid-19 On Opioid-Related Overdose Deaths In Texas, Karima Lalani, Christine Bakos-Block, Marylou Cardenas-Turanzas, Sarah Cohen, Bhanumathi Gopal, Tiffany Champagne-Langabeer

Faculty, Staff and Student Publications

Prior to the COVID-19 pandemic, the United States was facing an epidemic of opioid overdose deaths, clouding accurate inferences about the impact of the pandemic at the population level. We sought to determine the existence of increases in the trends of opioid-related overdose (ORO) deaths in the Greater Houston metropolitan area from January 2015 through December 2021, and to describe the social vulnerability present in the geographic location of these deaths. We merged records from the county medical examiner's office with social vulnerability indexes (SVIs) for the region and present geospatial locations of the aggregated ORO deaths. Time series analyses …

Prevalence Of Prediabetes And Diabetes Vary By Ethnicity Among Us Asian Adults At Healthy Weight, Overweight, And Obesity Ranges: An Electronic Health Record Study, William S Vicks, Joan C Lo, Lynn Guo, Jamal S Rana, Sherry Zhang, Nirmala D Ramalingam, Nancy P Gordon

Faculty, Staff and Student Publications

BACKGROUND: Asian adults develop Type 2 diabetes at a lower body mass index (BMI) compared to other racial/ethnic groups. We examined the variation in prevalence of prediabetes and diabetes among Asian ethnic groups within weight strata by comparing middle-aged Chinese, Filipino, South Asian, and White adults receiving care in the same integrated healthcare delivery system.

METHODS: Our retrospective cross-sectional U.S. study examined data from 283,110 (non-Hispanic) White, 33,263 Chinese, 38,766 Filipino, and 17,959 South Asian adults aged 45-64 years who were members of a Northern California health plan in 2016 and had measured height and weight. Prediabetes and diabetes were …

A Comprehensive Update On Cido: The Community-Based Coronavirus Infectious Disease Ontology, Yongqun He, Hong Yu, Anthony Huffman, Asiyah Yu Lin, Darren A Natale, John Beverley, Ling Zheng, Yehoshua Perl, Zhigang Wang, Yingtong Liu, Edison Ong, Yang Wang, Philip Huang, Long Tran, Jinyang Du, Zalan Shah, Easheta Shah, Roshan Desai, Hsin-Hui Huang, Yujia Tian, Eric Merrell, William D Duncan, Sivaram Arabandi, Lynn M Schriml, Jie Zheng, Anna Maria Masci, Liwei Wang, Hongfang Liu, Fatima Zohra Smaili, Robert Hoehndorf, Zoë May Pendlington, Paola Roncaglia, Xianwei Ye, Jiangan Xie, Yi-Wei Tang, Xiaolin Yang, Suyuan Peng, Luxia Zhang, Luonan Chen, Junguk Hur, Gilbert S Omenn, Brian Athey, Barry Smith

Faculty, Staff and Student Publications

BACKGROUND: The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the development of the community-based Coronavirus Infectious Disease Ontology (CIDO) in early 2020.

RESULTS: As an Open Biomedical Ontology …

Lenalidomide Promotes The Development Of Tp53-Mutated Therapy-Related Myeloid Neoplasms, Adam S Sperling, Veronica A Guerra, James A Kennedy, Yuanqing Yan, Joanne I Hsu, Feng Wang, Andrew T Nguyen, Peter G Miller, Marie E Mcconkey, Vanessa A Quevedo Barrios, Ken Furudate, Linda Zhang, Rashmi Kanagal-Shamanna, Jianhua Zhang, Latasha Little, Curtis Gumbs, Naval Daver, Courtney D Dinardo, Tapan Kadia, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero, P Andrew Futreal, Benjamin L Ebert, Koichi Takahashi

Faculty, Staff and Student Publications

There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies. Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiology of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem …

Detection Of Fibular Rotational Changes In Cone Beam Ct: Experimental Study In A Specimen Model, Nils Beisemann, Antonella M Tilk, Jula Gierse, Paul A Grützner, Jochen Franke, Jeffrey H Siewerdsen, Sven Y Vetter

Faculty, Staff and Student Publications

BACKGROUND: In syndesmotic injuries, incorrect reduction leads to early arthrosis of the ankle joint. Being able to analyze the reduction result is therefore crucial for obtaining an anatomical reduction. Several studies that assess fibular rotation in the incisura have already been published. The aim of the study was to validate measurement methods that use cone beam computed tomography imaging to detect rotational malpositions of the fibula in a standardized specimen model.

METHODS: An artificial Maisonneuve injury was created on 16 pairs of fresh-frozen lower legs. Using a stable instrument, rotational malpositions of 5, 10, and 15° internal and external rotation …

Recent Advances In Rapid Detection Techniques For Pesticide Residue: A Review, Lingyuan Xu, A M Abd El-Aty, Jong-Bang Eun, Jae-Han Shim, Jing Zhao, Xingmei Lei, Song Gao, Yongxin She, Fen Jin, Jing Wang, Maojun Jin, Bruce D Hammock

Faculty, Staff and Student Publications

As an important chemical pollutant affecting the safety of agricultural products, the on-site and efficient detection of pesticide residues has become a global trend and hotspot in research. These methodologies were developed for simplicity, high sensitivity, and multiresidue detection. This review introduces the currently available technologies based on electrochemistry, optical analysis, biotechnology, and some innovative and novel technologies for the rapid detection of pesticide residues, focusing on the characteristics, research status, and application of the most innovative and novel technologies in the past 10 years, and analyzes challenges and future development prospects. The current review could be a good reference …

Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a 2 week treatment with an HDAC6 inhibitor, administered 3 d after the last dose of cisplatin. Mechanical hypersensitivity in animals of both sexes treated with the HDAC6 inhibitor was temporarily reinstated by a single injection of the neutral opioid receptor antagonist 6β-naltrexol or …

Estimating The Optimal Linear Combination Of Predictors Using Spherically Constrained Optimization, Priyam Das, Debsurya De, Raju Maiti, Mona Kamal, Katherine A Hutcheson, Clifton D Fuller, Bibhas Chakraborty, Christine B Peterson

Faculty, Staff and Student Publications

Background: In the context of a binary classification problem, the optimal linear combination of continuous predictors can be estimated by maximizing the area under the receiver operating characteristic curve. For ordinal responses, the optimal predictor combination can similarly be obtained by maximization of the hypervolume under the manifold (HUM). Since the empirical HUM is discontinuous, non-differentiable, and possibly multi-modal, solving this maximization problem requires a global optimization technique. Estimation of the optimal coefficient vector using existing global optimization techniques is computationally expensive, becoming prohibitive as the number of predictors and the number of outcome categories increases.

Results: We propose an …

Therapeutic Efficacy Of The Humanized Jaa-F11 Anti-Thomsen-Friedenreich Antibody Constructs H2al2a And H3l3 In Human Breast And Lung Cancer Xenograft Models, Diala Ghazal, Fatma Zalzala, John C Fisk, Swetha Tati, Loukia G Karacosta, Susan Morey, James R Olson, Sally Quataert, Grace K Dy, Kate Rittenhouse-Olson

Faculty, Staff and Student Publications

The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration. To assess the potential therapeutic efficacy of these antibodies, four human cancer- mouse xenograft models were treated with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and …

Daphnia As A Sentinel Species For Environmental Health Protection: A Perspective On Biomonitoring And Bioremediation Of Chemical Pollution, Muhammad Abdullahi, Xiaojing Li, Mohamed Abou-Elwafa Abdallah, William Stubbings, Norman Yan, Marianne Barnard, Liang-Hong Guo, John K Colbourne, Luisa Orsini

Faculty, Staff and Student Publications

Despite available technology and the knowledge that chemical pollution damages human and ecosystem health, chemical pollution remains rampant, ineffectively monitored, rarely prevented, and only occasionally mitigated. We present a framework that helps address current major challenges in the monitoring and assessment of chemical pollution by broadening the use of the sentinel species Daphnia as a diagnostic agent of water pollution. And where prevention has failed, we propose the application of Daphnia as a bioremediation agent to help reduce hazards from chemical mixtures in the environment. By applying “omics” technologies to Daphnia exposed to real-world ambient chemical mixtures, we show improvements …

Scgwas: Landscape Of Trait-Cell Type Associations By Integrating Single-Cell Transcriptomics-Wide And Genome-Wide Association Studies, Peilin Jia, Ruifeng Hu, Fangfang Yan, Yulin Dai, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: The rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq data to achieve two goals: (1) to infer the cell types in which the disease-associated genes manifest and (2) to construct cellular modules which imply disease-specific activation of different processes.

RESULTS: scGWAS only utilizes the average gene expression for each cell type followed by virtual search processes to construct the null distributions of module scores, making it scalable to large scRNA-seq datasets. We demonstrated scGWAS in …

The Mechanisms Of Action Of Tumor Treating Fields, Justin C Moser, Ellaine Salvador, Karina Deniz, Kenneth Swanson, Jack Tuszynski, Kristen W Carlson, Narasimha Kumar Karanam, Chirag B Patel, Michael Story, Emil Lou, Carsten Hagemann

Faculty, Staff and Student Publications

Tumor treating fields (TTFields), a new modality of cancer treatment, are electric fields transmitted transdermally to tumors. The FDA has approved TTFields for the treatment of glioblastoma multiforme and mesothelioma, and they are currently under study in many other cancer types. While antimitotic effects were the first recognized biological anticancer activity of TTFields, data have shown that tumor treating fields achieve their anticancer effects through multiple mechanisms of action. TTFields therefore have the ability to be useful for many cancer types in combination with many different treatment modalities. Here, we review the current understanding of TTFields and their mechanisms of …

Tumor Microenvironment: Barrier Or Opportunity Towards Effective Cancer Therapy, Aadhya Tiwari, Rakesh Trivedi, Shiaw-Yih Lin

Faculty, Staff and Student Publications

Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME's individual components and their interplay at higher resolution. Deeper understanding of the immune cell's diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a …

Federated Learning Algorithms For Generalized Mixed-Effects Model (Glmm) On Horizontally Partitioned Data From Distributed Sources, Wentao Li, Jiayi Tong, Md Monowar Anjum, Noman Mohammed, Yong Chen, Xiaoqian Jiang

Faculty, Staff and Student Publications

OBJECTIVES: This paper developed federated solutions based on two approximation algorithms to achieve federated generalized linear mixed effect models (GLMM). The paper also proposed a solution for numerical errors and singularity issues. And showed the two proposed methods can perform well in revealing the significance of parameter in distributed datasets, comparing to a centralized GLMM algorithm from R package ('lme4') as the baseline model.

METHODS: The log-likelihood function of GLMM is approximated by two numerical methods (Laplace approximation and Gaussian Hermite approximation, abbreviated as LA and GH), which supports federated decomposition of GLMM to bring computation to data. To solve …